Micro Exam 4

Classic pattern of dermatophytosis is the

"ringworm" pattern of a ring of inflammatory scaling with diminution of inflammation toward the center of the lesion -Infections of smooth skin commonly present as erythematous and scaling patches that expand in a centripetal pattern with central clearing

Dermatophytosis/ Tineas/ Ringworm

(1) tinea capitis of the scalp, eyebrows and eyelashes (2) tinea barbae of the beard (3) tinea corporis of the smooth skin (4) tinea cruris of the groin (5) tinea pedis of the foot (6) tinea unguium of the nails

When was HIV proposed as the cause of AIDs?

* 1983* isolation of a retrovirus from the lymph nodes of patient with lymphadenopathy (LAV), proposed as cause of AIDS, later virus is called HIV-1

Influenza envelope glycoproteins

*HA (Hemagglutinin)*: Ligand for cell receptor (sialic acid sugars at cell surface); Helps fuse envelope and cell membrane (Penetration). *NA (Neuramidinase)*: Enzyme that cuts sialic acid during virus release

Is antibody sufficient protection from mumps?

*No* because of mump's ability to spread cell to cell

Are viruses living?

*Viruses are not living* (and are not made of cells), they are a replicating molecules at the "edge of life": virus particles outside of cells are inactive (no metabolism, no movement)

True/false: Target cells in Genital Tract or Rectum have been Clearly Identified

*false*: Target cells in Genital Tract or Rectum have not been Clearly Identified

Hepatitis A Vaccine

*inactivated* -Two IM doses 6 months to 1 year apart -Recommendations -Chronic liver disease -Illegal drug use -MSM -Receive clotting factors -Endemic regions-Travel: 2 weeks before traveling

Pneumocystis (carinii) jiroveci and Pneumocystis Pneumonia

-A small, unicellular fungus that causes pneumonia (PCP), the most prominent opportunistic infection in AIDS patients -This pneumonia forms secretions in the lungs that block breathing and can be rapidly fatal if not controlled with medication. -Pentamidine and cotrimoxazole

Possible causes of hepatits

-Alcohol -Drugs -Autoimmune Disease -Metabolic Disease -Viruses (>50%)

Aflatoxins

-Aspergillus flavus -Affects corn, peanuts, cottonseed, peanuts, and some tree nuts (can contaminate grains during storage) -Toxic and carcinogenic metabolites: acts primarily on liver -Aflatoxin levels monitored in developed countries

Blastomyces dermatitidis: North American Blastomycosis

-Blastomyces dermatitidis- causes blastomycosis -Dimorphic -Free-living species distributed in soil of a large section of the midwestern and southeastern U.S. -Inhaled 10-100 conidia convert to yeasts and multiply in lungs -Symptoms include cough and fever. -Chronic cutaneous, bone, and nervous system complications -Amphotericin B

Hyphae

-Can be formed by yeast (pseudohyphae or hyphae) or mold (hyphae) -Threadlike, tubular filaments -Collectively, the hyphae form a matlike structure called a mycelium -Colonies on agar look filamentous, hairy or woolly

Infections by Candida: Candidiasis

-Candida albicans -Widespread yeast -Infections can be short-lived, superficial skin irritations to overwhelming, fatal systemic diseases. -Budding cells of varying size that may form both elongate pseudohyphae and true hyphae -Forms off-white, pasty colony with a yeasty odor

Neonatal herpes simplex

-Classic "Cigarette Burn" -Devastating and often fatal; usually acquired during delivery -Infection of CNS

Congenital Transmission of CMV

-Clinical evidence of disease apparent in 1/10 of infected newborns: small size, microcephaly, intracerebral calcification, thrombocytopenia, hepatosplenomegaly (jaundice), rash -Hearing loss and Mental retardation are common -Risk highest if mother acquired CMV during pregnancy -Post-natal transmission: no disease in healthy full-term neonates

Cryptococcosis and Cryptococcus neoformans

-Cryptococcus neoformans causes cryptococcosis. -A widespread encapsulated yeast that inhabits soil around pigeon roosts -Common infection of AIDS, cancer or diabetes patients -Infection of lungs leads to cough, fever, and lung nodules -Dissemination to meninges and brain can cause severe neurological disturbance and death.

Coccidioidomycosis overview

-Distinctive morphology - blocklike arthroconidia in the free-living stage and spherules containing endospores in the lungs -Lives in alkaline soils in semiarid, hot climates and is endemic to southwestern U.S. -Arthrospores inhaled from dust, creates spherules and nodules in the lungs -Amphotericin B treatment

Common effects of viral mutations

-Drug resistance -Antigenic changes -Changes in host-cell recognition (can infect new species, tissues)

Viral genes

-Genes required for viral replication-Genes that suppress host DNA, RNA or protein synthesis

Immunity to fungi

-Healthy, immunocompetent people have a high innate resistance to fungi -Disease can mean barrier has been crossed -Disease can mean loss of immune defense

Passive immunization of Hepatitis A

-Hepatitis A in Travelers is 100x more frequent than typhoid fever -HNIG prophylaxis for travelers -May prevent or attenuate among household outbreak

Identifying fungi

-Important during systemic infections: helps anti-fungal drug selection -With a few exceptions, clinical signs and symptoms of fungal infections resemble those of bacterial infections -Mold or yeast (microscopy, culture): identity of some molds can be identified just by microscopy -Yeast identification: requires additional tests Immunological (presence of antigen or antibody) PCR

Kuru (prions ppt)

-Indigenous Fore People of Papua-New Guinea -Disease epidemic over decades in the early, mid-1900s -Trembling symptoms, ataxia (loss of motor control), behavioral changes (pathological laughter), etc, death -Ritual Cannibalism: eating parts of the deceased -Women and children would get the less desirable parts (brains), were more likely to get Kuru (a fatal neurodegenerative disease) -Practice now discontinued since, no new cases

Mumps virus

-Infects epithelial cells of respiratory tract -Spreads systemically by viremia -Infection of parotid gland, testes, and CNS can occur

Chronic hepatitis

-Inflammation of liver is active-Persists for more than 6 months-Increased alanine aminotransferase in serum

Lab diagnosis of pityriasis

-Laboratory diagnosis is made by direct visualization of the fungal elements on microscopic examination of epidermal scales in 10% KOH ("spaghetti and meatballs") -Lesions will fluoresce with a yellowish color upon exposure to a Wood lamp -Treatment usually consists of the use of topical azoles or selenium sulfide shampoo

How a prion can be infectious

-Misfolded PrPSc induces the misfolding of the normal PrPc protein to generate more PrPSc protein -Accumulation of PrPSc leads to neuronal damage

Diagnosis of Cryptococcosis and Cryptococcus neoformans

-Negative stain demonstrating encapsulated budding yeast -Biochemical tests, serological testing

Transmission of Hepatitis B

-Neonatal from Mothers Infected Blood -Predominate Mode WorldwideSexual Activity (50% of Cases) -Intravenous Drug Use (20% of Cases) -50% of IVDUs are Infected -1 HBV transmission occurs per 250,000 individuals transfused: Screen for HBcAg -Cause of 27% Cases Unknown

Treatment/prevention of prion disease

-No cure: drugs to manage or slow neurodegenerative symptoms -Prevention: food safety (monitoring of cow herds); stopping enrichment of herbivore animal feed with proteins from animal remains; don't eat brains -Concern: Corneal transplants can transmit CJD (what other tissues?); Do sterilization procedures destroy prion proteins or not?

Latent cycle (non-lytic)

-No production of viruses-Infected cell is not recognized by immune system; drugs that inhibit productive replication cycle do not affect virus in latent stage -DNA genome of virus is stably kept in infected cell -Only one or two viral RNA or proteins are produced (latency RNA or latency proteins) -Virus can reactivate (switch back to productive cycle) in response to various signals

Candida albicans

-Normal flora of oral cavity, genitalia, large intestine or skin of 20% of humans -Account for 80% of nosocomial fungal infections -Account for 30% of deaths from nosocomial infections -Thrush - occurs as a thick, white, adherent growth on the mucous membranes of mouth and throat -Vulvovaginal yeast infection - painful inflammatory condition of the female genital region that causes ulceration and whitish discharge -Cutaneous candidiasis - occurs in chronically moist areas of skin and in burn patients

Paracoccidioidomycosis

-Paracoccidioides brasiliensis -Distributed in Central and South America -Lung infection occurs through inhalation or inoculation of spores. -Systemic disease is not common. -Ketoconazole, amphotericin B, sulfa drugs

Candida diagnosis

-Presumptive diagnosis made if budding yeast cells and pseudohyphae are found; germ tube -Growth on selective, differential media differentiates Candida species

Systemic fungal infections

-Primary fungal pathogens: respiratory infections in healthy normal hosts (usually thermal dimorphs: saprophytic hyphae in decaying organic matter; yeast form in host) -Opportunistic pathogens: mostly restricted to immunocompromised hosts (most commonly Candida species such as C. albicans; Aspergillus species such as A. fumigatus, and Cryptococcus neoformans

Lymphocutaneous sporotrichosis: Sporothrix schenckii

-Sporotrichosis (rose-gardener's disease)‏ -Very common saprobic fungus that decomposes plant matter in soil -Infects appendages and lungs -Lymphocutaneous variety occurs when contaminated plant matter penetrates the skin and the pathogen forms a nodule, then spreads to nearby lymph nodes.

Non-systemic fungal infections

-Superficial or cutaneous mycoses (skin, hair, nails) -Ringworm infections (tineas) -Subcutaneous mycoses (dermis, subcutaneous tissue, muscle)

Dimorphic fungi

-The dimorphic fungal pathogens are organisms that exist in a mold form in nature or in the laboratory at 25° C to 30° C and in a yeast or spherule form in tissues or when grown on enriched medium in the laboratory at 37° C -are considered primary systemic pathogens -cause infection in both "normal" and immunocompromised hosts -involve the deep viscera after dissemination of the fungus from the lungs following its inhalation from nature Include Blastomyces dermatitidis, Coccidioides immitis , Histoplasma capsulatum, Paracoccidioides brasiliensis natural habitat is delimited to specific geographic regions infection due to a particular fungus is acquired by inhalation of spores from that specific environment and geographic location

Fungal psychotrophic agents

-Toxic metabolites —mushrooms used in religious, magical or cultural rites for centuries -Magic mushrooms: Psilocybin and psilocin -Lysergic Acid Diethylamide (LSD) was isolated from ergot

Cutaneous mycoses

-Typically include infections caused by dermatophytic fungi—dermatophytosis -fungi in the genera Trichophyton, Epidermophyton, and Microsporum -invade the skin, hair, or nails -keratinophilic and keratinolytic --are able to break down the keratin surfaces -invade only the upper, outermost layer of the epidermis, the stratum corneum

Fungi characterisitics

-Unicellular (Yeasts) or Multicellular (Molds, Mushroom) -Eukaryotes -Mostly aerobes, some anaerobic •Biochemically versatile (many produce antibiotics)-E.g. epidermal fungi capable of metabolizing keratin •Long division time compared to bacteria•Stain gram +, but cells are larger •Many medical fungi are dimorphic: can exist in either yeast (unicellular) or mold forms (multicellular, arranged in tubular structures called hyphae or pseudohyphae) -Some fungal pathogens exhibit thermal dimorphism: hyphae form at room temperature (25°C) and yeast form at 37°C

Mycetomas

-When soil microbes are accidentally implanted into the skin -Progressive, tumorlike disease of the hand or foot due to chronic fungal infection; may lead to loss of body part -Caused by Pseudallescheria or Madurella

First AIDS cases

-cases of Pneumocystis carinii pneumonia (PCP) in previously healthy men in Los Angeles, New York and san Francisco

Superficial mycoses

-colonize the keratinized outer layers of the skin, hair, and nails -elicit little or no host immune response and are nondestructive and asymptomatic--usually of cosmetic concern only

Ergot alkaloids

-grain is infected with Claviceps purpurea (ergot) -Contaminated rye -Gangrenous: necrosis of extremities -Alkaloids produce an a-adrenergic blockade (restricts blood flow)

Prions

-misfolded proteins, contain no nucleic acid cause transmissible spongiform encephalopathies --(TSEs) - holes in the brain common in animals scrapie in sheep & goats bovine spongiform encephalopathies (BSE), aka mad cow disease humans - Kuru, Creutzfeldt-Jakob Disease, etc.

Complications of Hepatitis B

0.5% of transient (acute primary) are fatal, fulminant hepatitis •15-25% of chronic infections end in untreatable liver cancer

Two critical events for making more virus copies

1) Production of viral proteins: • Structural proteins for virion assembly • Enzymes important to virus growth cycle 2) Replication of viral nucleic acid genome • Diverse replication strategies, depends on nature of viral genome

Incubation Period for cervical ca and HPV

1-4 years

Penetration of Host Cell by Naked Viruses

1. *Endocytosis*, followed by disruption (lysis) of acidified endosome: • Most common mechanism • Adenovirus attachment, penetration and uncoating at nuclear pore 2. *Translocation (via pore)*: • Rare mechanism• Poliovirus attachment, penetration and uncoating (shown here) - Here, penetration and uncoating occur as one combined step

Function of virion

1. *Protection*: Prevents nucleic acid in extracellular environment form mechanical damage, chemical damage, nucleases. 2. *Recognition:* Outer surface of virion contains ligands that interact with host-cell surface receptors. 1. Naked viruses: Viral ligands are at the capsid surface (or at spikes) 2. Enveloped viruses: Viral ligands are the viral glycoproteins in envelope 3. *Self-assemble in infected cell, are metastable*: (stable outside of cell, but able to release nucleic acid when infecting new cell)

Fungal reproduction

1. Anamorph (asexual, mitosis) budding or fission Spores 2. Teleomorph (sexual) cells in haploid hyphae fuse and form zygote Mating types of haploid yeasts fuse and form diploid Diploids can form sexual haploid spores (meiosis)

Endocytosis, Followed by Fusion of Viral Envelope with Host Cell Membrane

1. Attachment via receptors 2. Vesicle formation 3. Release of capsid

Fusion of Viral Envelope with Host Cell Membrane

1. Attachment via receptors 2. Viral envelope fuses with cell membrane 3. Release of capsid

Significant opportunistic fungi

1. Candida 2. Cryptococcus 3. Pneumocystis

Differences between our cells and fungal cells

1. Cytoplasmic membrane—contains ergosterol rather than cholesterol 2. Cell wall made of chitin and glucan (rigid structure

Families of viruses defined by what major categories?

1. Genome type (RNA or DNA) 2. Virion structure (capsid symmetry and envelope presence) 3. Genome architecture 4. Baltimore class

Some examples of viruses associated with transplants

1. HIV-1/HIV-2 2. Hepatits B and C 3. CMV (cytomegalovirus) 4. EBV (Epstein-Barr virus) 5. LCMV 6. West Nile Virus 7. HTLV-1

Uncoating (Disassembly and Localization) of viruses

1. Many DNA viruses need to localize their genomes in host cell nucleus: nucleocapsids travel by binding molecular motors on microtubules, and uncoat at nuclear pores. 2. Most RNA viruses uncoat in host cell cytoplasm

Examples of viruses with icosahedral capsid symmetry

1. Polio virus 2. Herpes Simplex Virus Type I 3. Cone like capsid of HIV

Alphaherpesvirus Infectious Cycle

1. infection of sensory ganglia leads to latent infection 2. Spontaneous reactivation, reinfection of skin cells, propagation to new host

Stages of Viral Multiplication (Growth, Replication) Cycle

1.*Attachment* - binding of virus to specific receptors on cell surface 2. *Penetration (entry)* - crossing through the cell membrane 3. *Uncoating (disassembly and localization)* -freeing viral genome from capsid coat and localizing it to the site of viral transcription/replication. 4. *replication* - viral genome replicated, virion protein components produced 5. *Assembly and maturation* - virion components assemble and get modified 6.*release* - viruses exit host cell to infect new cells For some viruses the penetration/uncoating steps or the assembly/maturation/release steps occur simultaneously.

HIV pathogenesis progression

1.Acute primary infection•Viremia of M-tropic HIV •Asymptomatic or flu-like symptoms: up to 3 months after infection, results in seroconversion (antibody in blood against virus) 2.Slow (persistent) infection and latency•Asymptomatic for 2 - 15 years, little bursts of viral infections kept in check by immune system•Helps propagate virus (individuals look healthy, may not know they are infected) 3.AIDS•Symptoms related to reduced immunity: T-tropic HIV depletes CD4+ T cells which play critical role (Helper T cells)•< 500 CD4+ T cells/μl blood: opportunistic infections arise•< 200 CD4+ T cells/μl blood: Clinical definition of AIDS•Opportunistic infections: PCP, TB, toxoplasmosis, Kaposi's sarcoma (herpesvirus), B-cell lymphomas)•AIDS dementia (microglia infection, neuroinflammation)

Viral infections transmitted from pregnant mother to fetus or newborn

1.Before birth, when blood-borne viruses cross the placenta into the fetal circulatory system 2.During birth, when passing through the birth canal 3.Shortly after birth, by breastfeeding

What are some cytopathic effects?

1.Loss of cell adherence to plastic, accompanied by cell rounding 2.Cell shrinkage 3.Cell-to-cell fusion leading to large multinucleated cells, called syncitia 4.Cell aggregation: a particularly useful form of cell aggregation used in virus identification is hemagglutination 5.Cytoplasmic or nuclear inclusion bodies: granules in infected cells where virus replication or assembly occurs; visualization requires a staining agent. 6.Visible alterations in nuclear chromatin 7.Cell lysis 8.Cell death by apoptosis 9.Transformation: uncontrolled cell proliferation, can lead to cancer

Chickenpox rash progression

1.Macule 2.Papule 3.Vesicle 4.Pustule 5.Crust

Effects of viral skin infections

1.Macules 2.Papules 3.Vesicles 4.Pustules: •Other symptoms of viral skin infection include ulcers and sarcomas

What are the 3 main routes of Viral Spreading to the CNS?

1.Neuronal (PNS) 2.Olfactory 3.Hematogenous (blood)

Anti-HIV drugs

1.Reverse transcriptase inhibitors: nucleoside analogs and non-nucleoside analogs (First anti-HIV drug was AZT) 2.Protease inhibitors 3.CCR5 Binding inhibitor 4.Fusion inhibitor 5.Integrase inhibitor • HAART therapy (highly active antiretroviral therapy): Combines several anti-HIV drugs • Chance that a virus simultaneously resistant to all drugs emerges is low

Viral infections before birth can cause...

1.Spontaneous abortions, stillbirths and neonatal deaths. e.g. variola virus (causes smallpox) (Poxviridae) 2.Severe congenital (present at birth) malformations, called teratogenic effects: deafness, blindness, and congenital heart and brain defects. e.g. Rubella virus (Togaviridae), cytomegalovirus (CMV), varicella-zoster virus (VZV) and herpes simples virus type 2 (HSV-2) (all Herpesviridae), Parvovirus B19 (Parvoviridae).

Hepatitis A incubation

15-50 days of incubation

When was adenovirus first isolated from tonsils/adenoids?

1953

What year was AIDS is first recognized as a new disease?

1981

When was HIV-2 discovered

1986-a second HIV is isolated from West Africa (HIV-2)

Hepatitis B symptoms

30% of individuals have no signs and symptoms •If symptoms occur, they are similar to hepatitis A + joint pain (immune complex disease) •Chronic hepatitis B infections occurs in 5-10% of cases •Chronic infections lead to:-Cirrhosis of liver-Hepatocellular carcinoma

Normal lifespan of Hepatocyte:

6 to 12 months; However, entire population can quickly replicate

Measles incubation period

7-13 days

Average incubation for hepatitis B?

80 days

How many major families exist of viruses?

> 23 major families of animal viruses able of infecting vertebrates

How many types of adenovirus serotypes?

> 50 human adenovirus serotypes:

Chromoblastomycosis

A progressive subcutaneous mycosis characterized by highly visible wart-like lesions Etiologic agents are soil saprobes with dark-pigmented mycelia and spores Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii Produce very large, thick, yeastlike bodies, sclerotic cells

Hepatitis U.S. Trends

A, B, C, D, E: 95% of acute viral casesHAV Most Common Cause of Acute Hepatitis InfectionHCV Most Common Cause of Chronic HepatitisAcute infection with a hepatitis virus may range from subclinical disease to self-limited symptomatic disease to fulminant hepatic failure (FHF)

Tropism

Ability and tendency to invade and replicate in certain cells or tissues, e.g. neurotropic viruses can replicate in the nervous system. What about lymphotropic and enterotropic viruses. Can be very limited (liver cells for hepatitis B virus) or very broad (vaccinia virus (a poxvirus) can infect almost any cell in culture).

Fulminant Hepatic Failure (FHF)

Acute Liver Failure in the Setting of Hepatic Encephalopathy -Increased Permeability of Blood-Brain Barrier -Impaired Osmoregulation in Brain-Results in Brain Swelling -50% Mortality 1% of Hepatitis A and B Infections

Prevalence of HPV

Approx. 5.5 million new cases of sexually transmitted HPV occur in the U.S. each year, with at least 20 million people currently infected.

Burkitt's Lymphoma

B Cell MalignancyGeographically limited; Malaria

Appearance of cheek in parvovirus B19

Both cheeks appear bright red as though they had been slapped

Oral thrush also known as...

C. albicans

Host cell receptors for HIV attachment

CD4: found at surface of CD4+ T cells, small amounts also present at surface of macrophages Co-receptor also needed: CXCR4 (T cell surface) and CCR5 (macrophage surface)

Cryptococcus neoformans affects what part of the body?

CNS

Recombination in RNA viruses

Can occur during RNA replication, can also occur between host cell mRNA and virus RNA (incoporation of new genes) - Speeds up RNA virus evolution

Antigenic shift of viruses

Change due to reassortment ->radical change (new virus never seen before, no one is immune, rapid spread)

Viral mutations

Changes in viral nucleic acid sequence occur during replication -> Misincorporation of wrong nucleotide base by DNA or RNA polymerase

Mycosis

Colonization of the host and resultant disease

Human infantile gastroentiritis:

Common disease caused by rotaviruses. Responsible for more than a million deaths per year, mainly from dehydration.

Antigenic drift of viruses

Continuous, gradual change in RNA sequence (changes surface glycoproteins H or N) -> why flu vaccination don't protect for life

Herpes physical appearance

DNA genome (100-200 kb, around 100 genes)• Icosahedral capsid, tegument layer, lipid envelope

Physical characteristics of adenovirus

DNA genome, no envelope, contains spike fibers and knobs (ligands for cell receptors)

Nucleic acid genome

DNA, RNA (single or double stranded)

Hepatitis D aka

Deltavirus

Fulminant Hepatitis

Develops in 0.1-0.3% of Hep A virus cases -80% mortality -Liver failure and encephalopathy -No immune complex-related symptoms

Cirrhosis:

Diffuse damage to hepatic parenchymal cells with nodular regeneration and fibrosis. The normal architecture is disturbed and blood flow is interrupted.

Viral damage to organs

Direct damage by cytocidal viruses--destruction of motor neurons (polio virus) •Epithelium of the Respiratory tract -Bacterial superinfection -destruction of lung parenchyma and alveolar epithelium -Blockage of airways •hypoxia •cascade leading to acidosis and fluid build-up •Epithelium of the Intestinal tract -Primarily rotaviruses -Children <24 months are symptomatic -Tips of the villi are damaged and/or fused -Absorptive surface area is lost -Fluid accumulation (diarrhea)

Tegument Layer (of Herpesviruses):

Disorganized protein layer between envelope and capsid found in Herpesviruses.

Complex Capsid Symmetry

Example: Poxviruses

Helical Capsule Symmetry

Examples: Influenza virus (enveloped virus) Tobacco mosaic virus (naked virus)

Recombination:

Exchange of genetic information between two near-identical (homologous) sequences of nucleic acid, can occur when different strains of same virus co-infect a cell

Reassortment of viruses

Exchange of genome segment. *Exclusive to viruses with segmented RNA genomes, such as Influenza virus.* Causes genetic shift (aka antigenic shift) in Influenza virus.

True/false: Viruses that cause systemic infections cannot replicate in white blood cells themselves.

False!! Viruses that cause systemic infections often replicate in white blood cells themselves (lymphocytes, macrophages).

Typical symptoms of acute jaundice

Fatigue Anorexia Abdominal pain Nausea and vomiting Dark urine Jaundice (occurs in 70-80% of individuals older than 14 years of age, less likely to occur in children)

Symptoms of chickenpox

First sign of disease is itchy exanthematous rash (average of 300-400 lesions on body) •Fever, malaise

Fulminant

From the latin fulmino, to hurl lightning. To occur suddenly with great intensity

Opportunistic infections

Fungal: Pneumocystis carinii pneumonia (PCP), Candida albicans infection of mouth and respiratory system, etc.•Bacterial (disseminated, pulmonary, pyogenic)•Protozoal•Viral (herpesviruses)•Opportunistic neoplasia (tumorous cell growth): Kaposi's sarcoma(caused by a herpesvirus), lymphomas

2 types of prion infection

Genetic (rarely transmitted): usually slow progression and onset is later in life Ingestion (transmitted): progression in months or few years

Rubella is also referred to as...

German measles

HDV overview

HDV is a dependovirus: it is missing a viral gene for successful replication in host cells, can only infect HBV-infected cell !Superinfection with HDV increases severity and pace of HBV infection (increases likely of developing fulminant hepatitis)In US, most common in IV drug abusers

Global distribution of HIV

HIV-1: Most of the World HIV-2: West-Central Africa 40.3 million people living with AIDs globally in December 2005

HPV & Cancer

HPV-16/HPV-18 and cervical cancer •HPV-16 present in 50% •HPV-18, -31, and -45 in 30% •HPV episomal DNA integrates into cellular DNA •Two HPV proteins, E6 and E7, bind and inactivate to cellular tumor suppression proteins (p53 and the retinoblastoma (Rb) gene product) •Essentially, normal cell cycle control is disrupted •Necessary but not sufficient: co-factors?

In 1996, what was the most prevalent type of STD in the U.S.?

HPV; now not the case due to vaccination

40% of acute hepatitis virus caused by

Hep A

Viruses that can cause hepatitis

Hepatitis A Virus Hepatitis B Virus Hepatitis Non-A Non-B Viruses: Hepatitis C, D, E, and G Viruses Other viruses can infrequently cause hepatitis: -Adenovirus -CMV -EBV -Herpes simplex (rarely)

Which hepatitis viruses cause chronic hepatitis infections?

Hepatitis B, C, D and G viruses

Pathogenesis of hepatitis

Hepatitis viruses enter the bloodstream-Carried to the liver-Infect the hepatocytes-As hepatocytes are damaged, liver cirrhosis and liver function impaired

Recombination in DNA viruses

Host cell enzymes responsible for homologous recombination

Epidemic keratoconjunctivitis (aka "shipyard eye"):

Human adenovirus type 8 (HAdV-8) infection following frequent eye injury by small foreign objects.

For viral infection to occur, cells need to be

I. *physically accessible*(depends on route of entry) II. *susceptible to the virus*: have receptors at surface for viral attachment, and entry. III. *Permissive for virus replication:* contain enzymes and materials needed to produce new virions (allow replication, assembly, and release).

Who is at risk in the U.S. of contracting HIV?

IV drug abusers, sexually active people with multiple partners (homosexual and heterosexual), prostitutes, newborns of HIV-positive mothers

Cytomegalovirus:

Infected cells form syncitia (enlarged multinucleated cells); with staining, central (owl's eye) inclusion body is visible

Original Definition of Viruses (1890's):

Infectious agents that can pass through bacteria-trapping filters

TSE pathologies (prions ppt)

Infectious protein resistant to digestion Infectious protein passes through enteric mucosa (how?) Spreads to enteric nervous system and lymphoid tissues (spleen, lymph nodes, Peyer's patches), then to CNS Pathology includes astrocytosis, vacuolization, and loss of neurons Plaques are sometimes present Limited or no involvement in immune response

Hepatitis B treatment and prevention

Interferon-alpha (chronic cases) -Famciclovir and Lamivudine in trial -Hepatitis B immune globulin-prophylatic measure -Hepatitis B vaccine -3 IM doses -subunit of HBsAg

Viral penetration: endocytosis

Internalization of coated pits at the cell membrane (most common)

What is one of the first prodromal symptoms of measles?

Koplik's spots

TSEs in humans (prions PPT)

Kuru Creutzfeldt-Jakob disease (CJD) Fatal familial insomnia (FFI) Gerstmann-Straussler syndrome (GSS) new variant Creutzfeldt-Jakob (nvCJD)

Poxviruses:

Large enveloped DNA viruses with ovoid or brick-shaped nucleocapsid

Viral envelope

Lipid bilayer acquired from host cell membrane, contains viral glycoproteins

Host range

List of species that a virus can infect. Can include only one species (e.g. poliovirus), or many (e.g. rabies virus).

Antigenic shift of viruses causing pandemics

Mixed infection of two species of Influenza (8 segments of RNA each). Assembly of virions with 8 segments (but can come from either parent species). •Responsible for Pandemic Strains: Influenza virus acquires new envelope glycoproteins (new H or new N) •Coinfection of organism (pig) with human influenza and usually avian (bird) influenza •Rare, but bound to occur eventually (every 20-25 years)•H1N1 (swine flu) 1918 Spanish flu: 20+ million died worldwide

Mutation rate of RNA viruses

Mutate much more quickly, leading to new virus strains or species. Causes genetic drift (aka antigenic drift) of Influenza virus.

DNA viruses rate of mutation

Mutate slowly (co-evolve with their host species)

Mycotoxicoses

Mycotoxins are secondary fungal metabolites that cause diseases, known collectively as mycotoxicoses, following ingestion, inhalation, or direct contact with the toxin Humans typically ingest crops infected with the fungi or poisonous mushrooms

Modern definition of a virus

Obligate intracellular parasites, molecular and ultramicroscopic in nature

Histoplasmosis aka

Ohio valley fever

Matrix Layer:

Organized protein layer between envelope and capsid, usually bound to inner face of envelope. Found in many enveloped viruses.

Icteric symptoms

Pale stools, jaundice, and dark urine

Measles Virus is part of the ______ family

Paramyxoviridae family:

Histological stains (no KOH) to diagnose fungal infections

Periodic Acid-Schiff (PAS) reaction Giemsa Stain

Hep A virus can be caused by

Poor hygiene/sanitation •Spread fecal-oral route -Contaminated water-Dirty hands (daycare center) -Contaminated food (restaurants) -Shellfish may become contaminated with sewage and may concentrate and retain viruses

Antiviral Drugs Against HSV Type 1 and 2

Prevent or shorten primary or recurrent disease; do not eliminate latent infection•Inhibitors of viral DNA polymerase- Acyclovir (Zovarix)- Related to acyclovir: Valacyclovir, Penciclovir, Famciclovir-Trifluridine (Viroptic): herpetic keratitis •Some are used only topically

Prevention of respiratory viral infections

Protection: mucus, coughing, sneezing, secreted IgA, alveolar macrophages

HIV virion structure

RNA Genome: mutates rapidly, many HIV-1 subtypes, mutates over the years in a patient (drug resistance) Envelope contains gp120 and gp41Matrix proteins (not shown )Core proteins (form capsid) Enzymes: reverse transcriptase, integrase, protease

Pustules

Raised legion filled with white pus. Can form around hair follicles.

Recurrence less or more serve in latent herpes virus

Recurrence less severe than primary infection

Virulence

Relative capacity of a pathogen to infect and cause harm to a host cell

Uncoating of viruses: viral replication

Release of genome from capsid •Some viruses loosen their capsid partially but do not release completely free genomes (poxvirus) •Some naked RNA viruses inject genome into cell at membrane (uncoating and penetration are one event)

Viral release

Release of newly formed virions to the extracellular environment. •Lytic viruses: Almost all naked viruses exit by causing cell lysis, some enveloped viruses are also lytic viruses. •Budding viruses: -Most enveloped viruses exit cell by budding at plasma membrane or by being secreted via the secretory pathway -May damage and kill cell, or not

What is the most common route of viral entry?

Respiratory tract

HIV is part of which family of viruses?

Retrovirus Family(Lentivirus subfamily)

Hypersensitivity pneumonitis (acute or chronic)

Rhinitis Bronchial asthma Alveolitis -Skin test to identify allergen -Fungal spore count monitoring

Rhinovirus attachment

Rhinovirus ligand: Canyons (grooves) on capsid surface bind ICAM-1.

HIV-1 and HIV-2 Genomes Are Related to

SIVs (Simian Immunodeficiency Viruses)

KOH prep to diagnose fungal infections

Skin is swabbed with 70% ethanol Surface scraped to remove skin or hair containing fungus Treated with 10% KOH Chitin wall is resistant (bacteria, human cells are lysed) Observe with microscopy for hyphae or cells

How do viruses enter the eye?

Small abrasions.

Vesicles

Small clear fluid-filled blister.

Papules

Small solid raised inflammatory (red) lesions. May open

Cell-to-Cell spread of viruses

Some viruses are transmitted from a cell to a neighboring cell without forming extracellular virions (see Figure below). •Avoids exposure of viruses to the outside of the cell and may limit exposure to the immune system•Infection can still spread over long distances within host body if infected cell is circulating white blood cell or a neuron.

Herpes spread by..

Spread by aerosol and/or direct contact (kissing, sexual contact)

Viral glycoproteins of envelope

Sugar-modified transmembrane proteins that function in virus attachment and entry into cells

Clinical Syndromes of Hepatitis A

Symptoms of acute hepatitis or no symptomsiResult of Immune-mediated liver damageiDisease milder in childreni4 to 6 days later icteric phasei2/3 adults jaundice . . . 1/5 to 1/10 childreniVirus shedding occurs 14 days prior to symptoms

Treatment of Cryptococcosis and Cryptococcus neoformans

Systemic infection requires amphotericin B and fluconazole.

Immune response to mono

T cells proliferate to fight infected B cells

Longevity of herpes

Tend to establish lifelong, latent infections that can reactivate to cause one or more rounds of disease

Conjunctiva

Thin membrane that covers the surface of the inner eyelid and the white part of the eyeball.

Rubella family

Togaviridae family

Candida treatment

Topical antifungals for superficial infections, amphotericin B and fluconazole for systemics

Herpes Simplex Latency in

Trigeminal Ganglia (TGN)

Histoplasmosis

Typically dimorphic Distributed worldwide, most prevalent in eastern and central regions of US Grows in moist soil high in nitrogen content Inhaled conidia produce primary pulmonary infection that may progress to systemic involvement of a variety of organs and chronic lung disease. Amphotericin B, ketoconazole

Shingles rash pattern

Usually unilateral dermatomal rash

Both chickenpox and shingles can spread

VZV

What is the only herpesvirus that spreads person-to-person by coughing or sneezing?

VZV

Genital herpes

Vesicles become confluent then ulcerate

How Membranes (Phospholipid Bilayers) Fuse

Viral fusion proteins bring two membranes very close together so they can fuse

Penetration of viruses: Viral replication

Virus must cross the cell membrane to reach the cytoplasm (and possibly the nucleus)•Some viruses are endocytosed before they penetrate into cytoplasm

Virion

Virus particle (form outside of cell)

secondary viremia

Virus replication in target organs may allow reentry of virus into blood

Define cytopathic effects?

Virus-induced damage or change in infected cells, visible with light, (or fluoscerent) microscope. Most, but not all, viruses cause CPE. Useful tool to help diagnose viral infections.

Attachment of viruses: Viral replication

Viruses attach to cell surface, requires viral ligands and host cell surface receptors

Routes of entry for viruses

Viruses gain entry into the host through the skinbreaches or one of the following mucous membranes. •Respiratory tract •Gastrointestinal tract •Urogenital tract •Conjunctiva (eyes)

How do viruses get from one host to another?

Viruses usually are shed through routes of entry -Respiratory tract mucus and saliva (talking, sneezing coughing) -Semen, cervical secretions, saliva (sexual transmission) -Feces (diarrhea) -Skin lesions (or contact) -Breast milk -Urine (more significant for zoonoses transmission) -Viremia —blood (sexual transmission, arthropod vector, contaminated blood products or needles)

Pityriasis (Tinea) Versicolor

Worldwide--tropical environments may affect up to 60% caused by Malassezia furfur disease of healthy persons --young adults are most commonly affected Direct or indirect transfer of infected keratinous material from one person to another -lesions of pityriasis versicolor are small hypo- or hyperpigmented macules Little or no host reaction occurs--lesions are asymptomatic possible mild pruritus or secondary infection of hair follicles in severe cases

Hepatitis B stats

Worlwide: 1 out of 3 person is infected with HBV (2 billions), 400 millions chronically infected, 1 million die/year-Mother-child transmission common •USA: 1 out of 20 person is infected (12 million), 1 million chronically infected, 5000 die/year of cirrhosis (80%) and hepatocellular carcinoma (20%) •High risk groups in US include-IV drug users-Hemodialysis patients-Persons with multiple sex partners-Institutionalized patients-Healthcare workers

70% hepatectomy, restoration within

a few days

Neoplasia

abnormal growth of cells

Dysplasia:

abnormal maturation of cells (usually increase in immature cells)

Aerial hyphae

above surface and usually produce conidia that contain airborne spores or cells

What population is at the greatest risk for sexually transmitted infections?

adolescents and young adults (age 15-24)

Transmission of mumps

aerosols

Vegetative hyphae

at surface or submerged, absorb nutrients

tinea pedis

athlete's foot

•Adult complications of chicken pox

bacterial superinfections of scratched lesions (scarring), interstitial pneumonia (inflammatory response)

Mucosal HPV cause

benign head and neck tumors (papillomas of mouth, larynx, conjunctiva), anogenital warts, and some can lead to cervical, vulvar, anal, and penile cancer

Nerve:

bundled neuronal axons

Ganglion:

bundled neuronal cell bodies

Viral entry into GU tract

can occur via minute abrasions from unprotected sexual activity. Prophylactic latex condoms impermeable to most viruses - Must be used properly, existing risk of condom breakage - Do not fully prevent sexual transmission of papillomaviruses: can be transmitted via contact of external surfaces not covered by condom; HPV vaccine can protect against some strains

What is the second most prevalent type of cancer worldwide in women?

cervical cancer (250,000 deaths)

Macules:

change of skin color (lighter, darker, redder) with no elevation, depression or change in skin texture

Varicella-Zoster Virus (VZV) causes

chickenpox(infection) and shingles (reactivation)

Post-herpetic neuralgia:

chronic pain syndrome in 30% of 65 yrs+ old patients with shingles; highly debilitating; can persists for months to years; narcotic medication if excrutiating pain

Chronic liver damage can result in

cirrhosis; Formation of fibrous tissues, nodules, scarring that interferes with liver function and blood circulation

Coccidioides immitis - causes

coccidioidomycosis

Conjunctivitis:

commonly called "pink eye". Can be caused by enterovirus type 70 (Picornaviridiae).

Subcutaneous mycoses location on the body

commonly introduced traumatically through the skin have a propensity to involve the deeper layers of the dermis, subcutaneous tissue, and bone

The 100+ HPV types can be divided into

cutaneous HPV and mucosal HPV

Herpes gladiatorum entry through

damaged skin of body

Koilocytes

dark, wrinkled nuclei surrounded by a clear halo (where new HPV virions are assembled). show CPE of HPV infection

Insidious:

disease that progresses gradually with inapparent symptoms

VZV lies latent in...

dorsal root ganglia (also more uncommon: latency in trigeminal ganglion-usually limited to one of the three branches)

DNA polymerase:

enzyme can detect mistakes and correct (proof-reading capability); error rate 10-8 to 10-11

HPV Replication: Viral Life Cell is Linked to

epithelial cell differentiation

Protection of the eye from viruses

eye blinking and tear secretions continually clean surface.

True/false: Patients with hepatitis always have jaundice

false.

True/false: Viral infections cannot be transmitted from pregnant mother to fetus or newborn

false: Viral infections can be transmitted from pregnant mother to fetus or newborn

True/false: HIV cannot be prevented by condoms

false; Condoms = "safer sex": consistent and proper usage of male latex condoms

Hepatits A spread by

fecal-oral route

Parvovirus B19 is also known as

fifth disease; erythema infectiosum

HIV envelope glycoproteins:

gp120 (glycoprotein 120): Ligand for cell receptor (CD4) gp41: Helps fuse envelope and cell membrane (Penetration)

Kopek's spots are usually located on.....

gums near molars

Acute liver infection can cause

hepatitis (liver inflammation).

Late complication of chronic hepatitis is

hepatocytic carcinoma

HPV is

human papilloma virus

Blood screening for CMV only done for blood destined for...

immunocompromised recipients

Multinucleated measles infected cell detected by

immunofluorescence

HPV is highly prevalent in what demographic of people

in women under 30 years of age. A 3-year study at a university in New Brunswick, NJ, found that 43% of female college students converted from HPV-negative to HPV-positive.

Corneal infections

infection of clear tissue over the iris and lens. Human herpes simplex virus type-1 (HSV-1) infection of the cornea can lead to blindness.

Hepatitis

inflammation of the liver

Mycotoxicoses basic definition

inhalation, ingestion, or direct contact of disease-causing fungal metabolites (poisoning)

Viruses were not visualized until

invention of electron microscope in 1931

Hepatocellular Carcinoma:

liver cancer (associated with Hep B and C, only)

Types of cutaneous HPV

many types, HPV-1 to HPV-4 are most common

MMR Vaccine prevents

measles, mumps, rubella

Five contemporary childhood exanthematous diseases

measles, rubella, roseola (HHV-6), chickenpox (VZV), and fifth disease (Parvovirus B19)

EBV remains latent in

memory B cells (tonsils, oropharynx) for the rest of a person's life

Chickenpox

mild disease of children; can be severe in infants, adults, and persons with impaired immune systems

What type of ailment do adenoviruses cause?

most cause upper respiratory tract infections, conjunctivitis, tonsillitis, hemorrhagic cystitis, and gastroenteritis (with diarrhea)-HAdV8: Epidemic Keratoconjunctivitis-HAdV14: Can be fatal-HAdV36: Has been linked to obesity Less common: aseptic meningitis, encephalitis, hepatitis and disseminated disease

Histoplasma capsulatum

most common true pathogen; causes histoplasmosis

Protection against viruses in the GU tract

mucus lining the tract, flushing away by urination, and mildly acidic environment of vagina (pH = 5-6).

Molds

multicellular, form tubular structures

Physical characteristics of measles virus

negative ss RNA, helical capsid, envelope

Anatomical distribution of shingles rash determined by

nerve in which reactivation occurred (and is usually unilateral)

Neurotropic viruses infect...

neurons

Prion proteins are produced by

neurons of animals

RNA polymerases (and reverse transcriptases of retroviruses)

no proof-reading capability; error rate 10-3 to 10-4

All virions contain a

nucleocapsid core (nucleic acid + capsid)

Dermatophytoses of the foot and hand may often become complicated by

onychomycosis in which the nail plate is invaded and destroyed by the fungus

Sacral ganglia are

paravertebral ganglia of the sympathetic trunk

Viral mechanisms to cross into brain

passing between blood capillary cells, infecting blood capillary cells, or infecting white blood cells that are able to move out of blood vessels.

Incubation period

period of time between initial infection and appearance of disease symptoms.

Rubella physical characteristics

positive ss RNA, icosahedral capsid, envelope

Blood-brain barrier

prevents infection of brain from most blood-borne pathogens: semi-permeable interface does not let macromolecules through, characterized by tight junctions between the endothelial cells of the blood capillary.

Tineas of hair bearing areas often present as

raised, circular or ring-shaped patches of alopecia with erythema and scaling or as more diffusely scattered papules, pustules, or vesicles

he smaller the (aerosol) particle, the more likely it is to

reach deep into the respiratory system; infection of mucosal cells

Viral penetration: translocation

receptor carries virus across membrane (rare)

HHV-6 causes

roseola (exanthem subitum = sudden rash), HHV-7 causes a similar disease •Rapid onset of high fever for a few days(can cause febrile convulsions) •Rash develops a few days later, lasting for 1-2 days -Faint maculopapular rash-Develops over neck, trunk, and buttocks •Supportive care (disease is self-limited)

Clinical Syndromes caused by adenovirus depend on...

serotype

Chronic persistent infection of liver by Hepatitis B or Hepatitis C can also cause

severe life-threatening cirrhosis (liver disease) or hepatocarcinoma (liver cancer). Other viruses may also infect and damage the liver during systemic infections.

Stachybotrys chartarum

sick building syndrome; severe hematologic and neurological damage

Structure of viruses

simple and symmetrical

Sinusoids:

small blood vessels with discontinuous endothelium; *more permeable*: less tight junctions, non-endothelial cells• Liver, Spleen, Bone Marrow, and Adrenal Glands •Lined with Macrophages-Liver: Kupffer cells-Hepatic viruses replicate in Kupffer cells or are transcytosed (transported across) to hepatocytes

Mycology

study of fungi

What do virokines do?

suppress immune response

capsid

symmetrical layer of protective viral proteins that surround and protect genome

During Genital Infections, HSV Establishes Latency in

the Sacral Ganglia

Dermatophytic infections that are localized and that do not affect hair or nails can usually be treated effectively with

topical agents; all others require oral therapy

Host-Host Transmission of HIV is hypothesized to occur via

transmission of virus-infected cells, instead of free virions

True/false: Adenovirus is frequent cause of tonsillitis unresponsive to antibiotic therapy

true

True/false: Hepatitis Viruses Come From Different Virus Families

true

True/false: Meningitis in 50% of cases(usually mild) of mumps

true

True/false: Most people have the herpesviruses CMV (cytomegalovirus) and EBV (Epstein-Barr virus) and show no symptoms

true

True/false: No Vaccine or Treatment for EBV

true

True/false: No virus or cell has found a way to transform the amino acid information in proteins into nucleic acid informatio

true

True/false: The nucleic acid genome of viruses needs to enter a host cell so copies of nucleic acid and new virus particles can be made

true

True/false: There is a theory that HIV emerged from interspecies transmission in 1940's or 50's

true

True/false: Virions can also package viral enzymes (e.g. RNA polymerase)

true

True/false: •Not transmitted by mosquitoes, touching, casual kiss, etc. (virion is fragile)

true

True/false: Fungi eukaryotic

true; Cells contain organelles such as nucleus, ER, Golgi, mitochondria

True/false: Virions can also package viral enzymes (e.g. integrase, protease, reverse transcriptase)

true; important in HIV/AIDs

Yeasts:

unicellular, grow by budding or unicellular fission. E.g. baker's yeast (bread, beer)

Coccidioidomycosis aka

valley fever

Type of transmission: mother to fetus/newborn

vertical transmission

How is HPV transmitted?

via fomites, direct contact, or sexual contact

Viral resistance to drug therapy

viral resistance to a single drug therapy can arise quickly (antigen drift within the host)

Enveloped viruses

virions also contain envelope acquired from infected host cell Envelope: lipid membrane + viral membrane proteins

Naked viruses

virions with no envelope

Viremia

virus infection of blood (free or in infected leukocytes)

Viral penetration: fusion

virus membrane fuses with the cell membrane, thus, internalizing virus capsids (and tegument proteins)

Localized infection:

virus remains near site of entry (epithelium)

Systemic infection

virus spreads beyond initial site infection (to subepithelium), to affect many organs. Systemic dissemination usually first involves spreading from the initial site of infection to the regional lymph nodes and then to the bloodstream, causing a primary viremia.

Molecular virus structure

virus structure is very simple (and symmetrical), consists of a nucleic acid genome (RNA or DNA), a protective protein coat, and sometimes, a lipid envelope -*No organelles or ribosomes*, small genome does not encode all the genes required to replicate without a host cell

Cutaneous HPV cause

warts (common, plantar, flat)

Incubation period for HPV warts and papillomas is

weeks to months

Dermatophytoses

wide range of clinical presentations, affected by: species of dermatophytes inoculum size site of infection immune status of the host

Baltimore Classification

• All viruses must make mRNA for host ribosomes to translate. • Nobel laureate David Baltimore proposed to classify viruses according to the pathway used to produce mRNA from viral genome • Hepadnaviruses constitute a seventh VIIclass: ds gapped DNA genomes that require RT for replication

The Betaherpesvirus Subfamily

• CMV, HHV-6, and HHV-7 • Replication in monocytes, lymphocytes, epithelial cells • Latency in monocytes and lymphocytes (T cells mainly for HHV-6 and -7) • CMV spread by close contact including sexual contact (body secretions: infection of secretory glands and kidney), blood transfusions and organ transplant, mother-fetus • HHV-6 and HHV-7 spread by saliva

HIV pathogenesis

• Complex • HIV is initially M-tropic (short acute infection)• Years of prolonged chronic infection and latency (asymptomatic) •HIV eventually mutates to T-tropicvirus • Decreasing CD4+ T cells and increasing virus load • AIDS and AIDS dementia

The Gammaherpesvirus Subfamily

• EBV, KSHV (HHV-8) • EBV replication in B cells and epithelial cells • KSHV replication in lymphocytes and other cells• Latency in B cells • EBV spread by saliva (kissing disease) • KSHV spread to be determined (close contact)

Evolution of HIV

• HIV (Human Immuno-deficiency Virus): retrovirus that causes AIDS; RNA virus with reverse transcriptase • Over years, HIV in a patient continues to evolve• HIV evolved from SIV (Simian Immuno-deficiency virus), continues to involve (HIV-1, HIV-2, etc.)

HPV physical characteristics

• Naked, icosahedral capsid, ds circular DNA genome

Measles symptoms

• Prodrome (early symptoms) for 2 days: High fever and CCC and P- C: cough- C: coryza (head cold)- C: conjunctivis- P: photophobia • Syndrome: Koplik spots, then maculopapular rash • Complications: - Pneumonia, with possible subsequent bacterial superinfection (60% of deaths due to measles)- Encephalitis

Alimentary Tract (Oral-Fecal Transmission) viral entry

• Second most common route of viral entry • Stomach plays central protective role: high acidity of stomach (pH=2), proteases• Additional protection: mucus, bile detergents, secreted IgA, phagocytes, (vomiting, diarrhea) • Most enteric viruses are resistant to stomach- HIV not resistant, but bypass via unprotected anal intercourse (infection of M cells)

HSV Lab Diagnosis

• Tzanck smear (scraping of base of lesion), Papanicolaou smear (pap smear): look for specific CPEs (syncitia, intranuclear inclusions, ballooning cytoplasm) • Virus culture on cell lines • PCR analysis

Chronic persistent hepatitis complications

•20 to 30% of patients develop cirrhosis •1 to 5% will develop liver cancer in 10 years

Transmission of adenovirus

•Aerosol •Close contact •Fecal-Oral

Viral assembly

•All of the components of the virus assembled into a particle (genome, capsid proteins, etc.) •Tends to occurs at specific sites within the infected cell •Virus particle not infectious until maturation •For some viruses two or three of these last steps occur simultaneously: assembly-maturation-release •Assembly of virion capsid assembly: viral factories (site of assemly of many capsids) often visible by EM-Sometimes can even be seen as inclusion bodies visible by light microscopy

Hepatitis C treatment

•Alpha-2 interferon •Alpha-2 interferon + Ribavirin-Rebetron-Hemolytic anemia (monitor hemoglobin)

What are the 3 major herpes subfamilies?

•Alphaherpesviruses: rapid replication, destroy infected cells, latency in sensory neurons; e.g. HSV-1 and VZV •Betaherpesviruses: slow replication, enlarge cells, latency in monocytes and T lymphocytes (found in kidney and secretory glands), etc.; e.g. CMV •Gammaherpesviruses: lysis of B or T cells, latency in lymphoid tissue; e.g. EBV

HIV Replication

•Attachment (gp120 binds to CD4 and co-receptor) followed by viral envelope fusion with cytoplasmic membrane (gp41) •RNA genome of retroviruses is reverse transcribed into DNA (by reverse transcriptase) and integrated into the host chromosomal DNA (by integrase)- Integrated viral DNA called a provirus: is there until cell dies, is replicated if cell divides •Genes of the integrated viral genome are transcribed into mRNA to make viral proteins •RNA genome assembled into capsid, exit by budding, virion maturation requires the action of the viral protease

Epstein-Barr Virus (EBV)

•Children usually have subclinical disease•Infectious mononucleosis: Teenagers and adults •Causes 79% of infectious mononucleosis cases (CMV causes the other 21%) •Common infection throughout the world. •Most frequently strikes students in high school or college in the U.S. •Often referred to as the "kissing disease." •Most people become infected with EBV during some time in their lives .•In developing countries (mostly in equatorial Africa), EBV infection is associated with African Burkitt's Lymphoma (role of malaria) •Facilitates appearance of Hodgkin lymphomas

Rubella overview

•Congenital Disease: cataracts, mental retardation, deafness • High mortality rate of infected fetuses and newborns under a year • Rash, swollen glands, and fever in children • Complications possible in adults • Maternal antibodies prevent spread of virus to fetus (vaccination)

CMV and neonates/immunocompromised pt

•Congenital syndrome in neonates •Infectious mononucleosis with prolonged fever and hepatitis •Pneumonia in bone marrow recipients •Disease syndromes in lung, liver, kidney and heart transplant recipients •Retinitis in AIDS patients

Betaherpesvirus subfamily

•Cytomegalovirus (CMV) (asymptomatic, congenital defects) •Human Herpesvirus-6 (HHV-6) (roseola infantum) •Human Herpesvirus-7 (HHV-7) (roseola-like)

Kidney & hepatitis

•Damage from immune complex deposition (antigen-Ab complexes) •Primarily hepatitis B virus

Laboratory Diagnosis of Viral Hepatitis Infections

•Diagnosis based on: -Symptoms -Blood tests for liver enzymes -Viral antibodies (e.g. IgM) -Viral genetic material (e.g. RT-PCR or PCR) *Blood Samples are Tested for Two Liver Enzymes: Aspartate aminotransferase (AST) and Alanine aminotransferase* •These enzymes are normally found in the liver but spill into the blood if the liver is damaged, thus raising the enzyme levels in the blood .•Nucleic acid tests (PCR, RT-PCR) to detect viral genomes are only available in specialized laboratories. •Patients with chronic hepatitis are harder to diagnose because these patients do not have nausea or jaundice until the liver damage is very advanced.•Serology (detection of IgM antibodies) is used to detect HAV, HBV and HCV.

HHV-6 and HHV-7 stage of life most commonly seen?

•Early childhood viruses: Affects 45 %of infants by 2 years

Gammaherpesvirus subfamily

•Epstein-Barr Virus (EBV) (mononucleosis, Burkitt's lymphoma) •Kaposi's sarcoma associated Herpesvirus (KSHV)

Symptoms of infectious mononucleosis

•Exudative pharyngitis •Fever •Swollen Lymph Nodes •Malaise •Enlarged spleen (sometimes) •Enlarged liver (sometimes) •Heart problems (rare) •Central nervous system (CNS) problems (rare) •Symptoms usually resolve within 1 or 2 months.

Cytomegalovirus (CMV)

•For the majority of people, CMV is not a serious disease -Infections of healthy individuals are typically subclinical (asymptomatic) -Once infected, CMV remains dormant within the person's body for life-Reactivation if immune health deteriotates •Opportunistic pathogen of immunocompromised individuals •Most prevalent viral cause of congenital disease: 0.5-2.5% newborns are infected

CMV Treatment

•Gancyclovir, valganciclovir, cidofovir, foscarnet: for immunosuppressed patients •Prevention: sexual transmission (latex condom usage, abstinence); screening of blood supply and organ donors. •Seropositive mothers are least likely to give birth to symptomatic infants: unfortunately, no vaccine

Pathogenesis of hepatitis C

•HCV infects Hepatocytes -acute -chronic •non-cytolytic•chronic persistent hepatitis •progression to cirrhosis and liver failure

VZV treatment

•Healthy unimmunized children: antiviral drugs not recommended; prevent scratching- Before vaccine, infection of children used to be encouraged (mild disease & lifelong immunity) •Exposed nonimmune pregnant woman, or immunocompromised patients: -Varicella-zoster immunoglobulin (VZIG) -Must be administered before the onset of disease •Chemotherapy available-Acyclovir, famcyclovir, valacyclovir •Treat pain of shingles patients (analgesics, painkillers, topical anesthetics, narcotics)

Types of symmetry of a capsid in viruses

•Helical symmetry •Icosahedral symmetry •Complex symmetry (rarer)

Alphaherpesvirus subfamily

•Herpes Simplex viruses: HSV-1 (oral herpes) & HSV-2 (genital herpes) •Varicella-zoster virus (VZV) (chickenpox, reactivation causes shingles)

Hepatitis A overview

•Inapparent but productive infections-90% of infected children-25 to 50% of infected adults

Minimum viral infectious dose

•Infection usually requires high viral infectious doses (from individual with high viral loads): enough viruses to survive or overwhelm the defenses at body surfaces. Dose required depends on state of host immune system. - Aerosol droplet from sneeze (100 million virions of rhinoviruses)- 1 mL of blood during HIV-1 infection (100 million HIV virions) •Viruses not spread by direct contacts between hosts can experience environments that inactivate virus particles: heat, low or high pH, adhesion to inanimate surfaces, exposure to sunlight, osmotic shock and dilution.

HPV and skin

•Infects epithelial cells of skin or mucous membranes •Persists in basal layer, active in differentiated cells

Disease Mechanism for Herpes Simplex Viruses (HSV-1 & HSV-2)

•Initial Lesion from Direct Contact •Detectable Cytopathology •Cell to Cell Spread (Syncytia): Ab avoidance •Latency in neuronal ganglia: Reactivation

EBV Transmission and Pathogenesis

•Intimate contact with saliva of an infected person. -Kissing -Sharing beverages -Sharing eating utensils. •Incubation period ranges from 4-6 weeks. •Latency with diseaserecurrence orasymptomatic shedding

Shingles or Herpes Zoster

•Latent VZV in dorsal root ganglia or trigeminal ganglion can be reactivated later in life after the age of 60 and the risk of reactivation increases with age (more common and severe in immunocompromised patients; chronic shingles in AIDS patients) •Severe pain precedes rash for several days •Vesicular rash forms in a 3-5 day period -The rash follows a nerve on one side of the body: occurs on a dermatome; zoster=belt or girdle -Disease lasts 10-15 days (3-4 weeks if immunocompromised)

Chickenpox Vaccine

•Live attenuated Oka strain •Childhood vaccination-Breakthrough varicella-zoster: non-attenuated virus mutant produces mild or regular chickenpox (contagious) 0.3-3.8% of cases •Vaccination of elderly (60+) available to reduce shingles incidence

Pathogenesis adenovirus

•Lytic infection of mucoepithelial cells •Latent infection of adenoid and lymphoid cells• Viremia may occur (immunocompromised) •Fecal-oral route or to eye (autoinoculation)

Hepatitis C (HCV): Major Public Health Problem

•Many infected people show few or no signs of disease for years and even decades ("silent epidemic"). •HCV infection common in the developed world. •~1.8% of U.S. population is infected with HCV (4 millions) •170 million carriers throughout the world

Detection of HPV

•Many infections are subclinical and may not be observed by physical exam or cytology •HPV DNA tests are MOST effective •5% of all Pap smears contain HPV-infected cells, 10% of them will develop cervical dysplasia (pre-cancerous state) •Despite 50 million Pap smears per year, we have ~12,000 annual cases of cervical cancer with 4,000 deaths •Annual Cost burden: $1.6 billion to $6 billion

Treatment and prevention of HPV

•Many warts regress naturally (but take months to years) •Wart removal by cryotherapy (liquid nitrogen), electrocautery, or chemical means (e.g. salicylic acid) •Imiquimod stimulates innate and inflammatory response, cidofovir selectively kills HPV-infected cells•Anti-HPV vaccine (Gardasil): protects against the HPV types 6, 11, 16, and 18, but does not protect against all types.-Immunization of girls prior to sexual activity (three shots starting at 11 years old) -Immunized women should still undergo regular pap smears

Fifth's disease adult infection

•May show no symptoms, develop the typical rash of fifth disease, polyarthritis (joint pain/swelling), or both •Polyarthritis:-Usually, joints on both sides of body are affected, most frequently hands, wrists, and knees-Joint pain and swelling usually resolve in 1-2 weeks, but may last several months •Complications:-patients with sickle cell anemia-Fetal congestive heart failure if mother gets encounters parvovirus B19 for first time during pregnancy •About 50% of adults have been previously infected with parvovirus B19, have developed immunity to the virus, and cannot get fifth disease

Fifth's disease overview

•Mild rash illness that occurs most commonly in children •The ill child typically has a "slapped-cheek" rash on the face and a lacy red rash on the trunk and limbs •An ill child may have a low-grade fever, malaise, or a "cold" a few days before the rash breaks out •The child is usually not very ill, and the rash resolves in 7 to 10 days •Lifelong immunity to parvovirus B19 (neutralizing antibodies) •Infected individuals contagious during early part of illness (cold-like prodrome), before rash appears •Transmission most likely occurs via respiratory droplets and oral secretions

Kaposi's Sarcoma associated Herpesvirus (KSHV)

•Mostly restricted to Mediterranean regions and countries (Greece, Italy, Northern Africa), and to AIDS patients •Causes Kaposi's sarcoma in AIDS patients

Structure of parvovirus B19

•Non-enveloped, icosahedral capsid •Single-stranded DNA virus

Fifth's disease treatment and prevention

•None •Vaccines for dog and cat parvoviruses (serious, lethal disease in pets)

Environmental Survival of Viruses

•Nonenveloped (more resistant) vs. enveloped viruses (more sensitive)-Drying, detergents, pH extremes, temperature extremes •In human or animal waste: organic matter protect virus •Human viruses in water-Intestinal viruses

Organs and tissues without sinusoids and infections

•Organs and tissues without sinusoids can also be infected: virus spread across fenestrated (more porous) capillaries, or via entry of infected leukocyte

Skin breaches of viruses

•Outermost layer of skin does not allow viral replication: dead keratinized cells, dry, mildly acidic •Minor Trauma-Herpes simplex viruses (HSV)-Papillomaviruses (HPV) •Insect bites-Dengue fever-West Nile virus-Yellow fever •Injection-Hepatitis B and C viruses-HIV, HTLV-CMV-Ebola •Animal bites-Rabies virus

Types of HPV

•Over 100 types: can cause causes outgrowth of cells (warts)•Some types can cause genital cancer (cervix, vulva, vagina, anus, and penis)

Why don't viruses get stuck on the cellular receptors as they are released from the host cell?

•Problem: exiting viruses would re-enter the (dying ?) infected cell they came from •Solution: Viruses will destroy host-cell receptor of infected cell -Neuraminidase (N), one of the two glycoproteins in the Influenza virus envelope, is an enzyme that cleaves the sialic acid receptor at infected cell surface as viruses are released•Viruses will inhibit the production of surface membrane proteins in infected cell -Inhibition of exocytosis, inhibition of host protein translation, inhibition of host mRNA transcription

Common viruses with a latent cycle

•Retroviruses (e.g. HIV)-Reverse transcribe their RNA genome into DNA, and integrate it in host cell chromosome (provirus form of virus genome)-During latency, integrated provirus will also be replicated as latently infected cell divides •Herpesviruses (e.g. HSV-1, VZV, EBV)- DNA kept as episome (stable DNA molecule) in host nucleus-Latency only in specific cell types or tissues (neurons for some, B cells for others, etc.)-Reactivate to reinfect cells in response to various factors: extreme temperature, physical trauma, stress, immune suppression

Fungi as infectious agents

•Saprobes (organic decay) or parasites •A few primary pathogens and many opportunistic pathogens (yeasts and molds)

CMV Transmission via Blood Transfusion and Organ Transplantation

•Screening for CMV virus (transfusion to pregnant mothers and immunocompromised patients; all organ transplants) •Transfusion: symptoms resemble mononucleosis and appear about 3-5 weeks after exposure •Transplantation: Allograft dysfunction, decreased survival of transplant recipient •Failure of many kidney transplants due to CMV (from transplanted kidney or from host)

Viral evolution

•Selective pressure-Immune system, antivirals, climate, etc. -Survival of the survivors •DNA viruses tend to co-evolve w/ one host species •RNA viruses: broader niche (often, many species) -50% of the genome can harbor mutations -10-kb viral genome = 45000 possibilities

Hepatitis C transmission

•Similar to HBV •Spread almost exclusively through blood contact. •Donated blood screening for HCV did not begin until 1992 ! •Incubation period is 6-7 weeks.•If signs or symptoms are present, they are similar to other hepatitis infections. •Between 55-85% of infected persons experience a chronic infection, resulting in chronic liver disease. •Chronic infection can lead to cirrhosis of the liver and hepatocytic carcinoma in 5-20% of infected persons

Epidemiology of Hepatitis C

•Spread is primarily via contaminated blood- blood products and organ transplants (before screening in 1992) - Shared Needles - Tattooing, body piercing •Other routes - Sexual contact - Maternal transmission

Viral maturation

•Stage in the life cycle of the virus when it becomes infectious •Viral or cellular proteases often involved-One or more of the capsid or envelope proteins may undergo a specific proteolytic cleavage, e.g. HIV

Treatment and prevention of adenovirus

•Supportive; no treatment for infection•Careful handwashing and chlorination of swimming pools

Size comparisons of cells, bacterium, and viruses

•Typical human cells (10-20 μm) •Typical bacteria diameter (1-5 μm) •Typical virus diameter: 30-100 nm (0.03-0.1 μm)•μm = 10-6 m•nm = 10-9 m *Viruses are ultramicroscopic: Smaller than cells (less than 1 μm)*

Icosahedral Capsid Symmetry

•Usually 20-sided •Simplest icosahedral capsid consists of triangular faces •Protruding fibers and knobs in some naked viruses (adenovirus)

Physical characteristics of hepatitis viruses

•Virions with RNA or DNA genomes, with icosahedral or helical capsids, with envelope or without

Herpetic Keratitis

•Virus travels along the opthalmic branch of the Trigeminal nerve •Symptoms-gritty feeling in eye-conjunctivitis-sensitivity to light •Recurrent infection may lead to loss of vision!

Jaundice

•Yellow color in the skin, mucous membranes, or eyes. •Occurs when liver is not functioning properly. •Yellow pigment is from bilirubin, a byproduct of old red blood cells.