Exam 4

Name the 2 types of bacteriophage life cycles and state what the bacteriophage capable of each is called.

1. Bacteriophages that replicate through the lytic life cycle are called lytic bacteriophages, and are so named because they lyse the host bacterium as a normal part of their life cycle. 2. Bacteriophages capable of a lysogenic life cycle are termed temperate phages. When a temperate phage infects a bacterium, it can either replicate by means of the lytic life cycle and cause lysis of the host bacterium, or, it can incorporate its DNA into the bacterium's DNA and become a noninfectious prophage.

List 4 shapes of viruses.

1. Helical viruses consist of nucleic acid surrounded by a hollow protein cylinder or capsid and possessing a helical structure. 2. Polyhedral viruses consist of nucleic acid surrounded by a polyhedral (many-sided) shell or capsid, usually in the form of an icosahedron 3. Enveloped viruses consist of nucleic acid surrounded by either a helical or polyhedral core and covered by an envelope 4. Binal (complex) viruses have neither helical nor polyhedral forms, are pleomorphic or irregular shaped, or have complex structures

Describe what an animal virus consists of structurally.

1. A genome The viral genome is a single or segmented, circular or linear molecule of nucleic acid functioning as the genetic material of the virus. It can be single-stranded or double-stranded DNA or RNA (but almost nevern both), and codes for the synthesis of viral components and viral enzymes for replication. It is also becoming recognized that viruses may play a critical role in evolution of life by serving as shuttles of genetic material between other organisms. 2. A capsid The capsid, or core, is a protein shell surrounding the genome and is usually composed of protein subunits called capsomeres. The capsid serves to protect and introduce the genome into host cells. Some viruses consist of no more than a genome surrounded by a capsid and are called nucleocapsid or naked viruses. Attachment proteins project out from the capsid and bind the virus to susceptible host cells. 3. An envelope Most animal viruses also have an envelope surrounding a polyhedral or helical nucleocapsid, in which case they are called enveloped viruses.

Describe the steps involved in the lytic life cycle of bacteriophages.

1. Adsorption Attachment sites on the bacteriophage adsorb to receptor sites on the host bacterium (see Fig. 4). Most bacteriophages adsorb to the bacterial cell wall, although some are able to adsorb to flagella or pili. Specific strains of bacteriophages can only adsorb to specific strain of host bacteria. This is known as viral specificity. 2. Penetration In the case of bcteriophages that adsorb to the bacterial cell wall, a bacteriophage enzyme "drills" a hole in the bacterial wall and the bacteriophage injects its genome into the bacterial cytoplasm (see Fig. 5). Some bacteriophages accomplish this by contracting a sheath (see Fig. 6) which drives a hollow tube into the bacterium. This begins the eclipse period. The genomes of bacteriophages which adsorb to flagella or pili enter through these hollow organelles. In either case, only the phage genome enters the bacterium so there is no uncoating stage. 3. Replication Enzymes coded by the bacteriophage genome shut down the bacterium's macromolecular (protein, RNA, DNA) synthesis. The bacteriophage replicates its genome and uses the bacterium's metabolic machinery to synthesize bacteriophage enzymes and bacteriophage structural components 4. Maturation The phage parts assemble around the genomes 5. Release Usually, a bacteriophage-coded lysozyme breaks down the bacterial peptidoglycan causing osmotic lysis and release of the intact bacteriophages 6. Reinfection From 50 to 200 bacteriophages may be produced per infected bacterium.

Name at least 2 fungal virulence factors that damage the host.

1. Like bacteria, fungal PAMPs binding to PRRs can trigger excessive cytokine production leading to a harmful inflammatory response that damages tissues and organs. 2. As fungi grow in the body, they can secrete enzymes to digest cells. These include proteases, phospholipases, and elastases. In response to both the fungus and to cell injury, cytokines are released. As seen earlier under Bacterial Pathogenesis, this leads to an inflammatory response and extracellular killing by phagocytes that leads to further destruction of host tissues. 3. Many molds secrete mycotoxins, especially when growing on grains, nuts and beans. These toxins may cause a variety of effects in humans and animals if ingested including loss of muscle coordination, weight loss, and tremors. Some mycotoxins are mutagenic and carcinogenic. Aflatoxins, produced by certain Aspergillus species, are especially carcinogenic. A mold called Stachybotrys chartarum is a mycotoxin producer that has been implicated as a potential serious problem in homes and buildings as one of the causes of "sick building syndrome." Mycotoxin symptoms in humans include dermatitis, inflammation of mucous membranes, , cough, fever, headache, and fatigue.

List 3 criteria used to define a virus.

1. The vast majority of viruses contain only one type of nucleic acid: DNA or RNA, but not both. 2. Viruses are totally dependent on a host cell for replication. (They are strict intracellular parasites.) 3. Viral components must assemble into complete viruses (virions) to go from one host cell to another.

Briefly describe yeasts and state how they reproduce asexually

1. Yeast are unicellular fungi which usually appear as oval cells 1-5 µm wide by 5-30 µm long. 2. They have typical eukaryotic structures. 3. They have a thick polysaccharide cell wall. 4. They are facultative anaerobes. Yeasts reproduce asexually by a process called budding (see Fig. 1 and Fig 6). A bud is formed on the outer surface of the parent cell as the nucleus divides. One nucleus migrates into the elongating bud. Cell wall material forms between the bud and the parent cell and the bud breaks away.

Name at least 3 fungal virulence factors that promote fungal colonization.

1. contact host cells; 2. adhere to host cells and resist physical removal; 3. invade host cells; 4. compete for nutrients; 5. resist innate immune defenses such as phagocytosis and complement; and 6. evade adaptive immune defenses.

Briefly describe 3 ways protozoans may reproduce asexually.

1. fission: One cell splits into two. 2. schizogony: A form of asexual reproduction characteristic of certain protozoa, including sporozoa, in which daughter cells are produced by multiple fission of the nucleus of the parasite followed by segmentation of the cytoplasm to form separate masses around each smaller nucleus. 3. budding: Buds form around a nucleus and pinch off of the parent cell.

temperate phage

A bacteriophage having a lysogenic life cycle and capable of inserting its DNA into that of the host bacterium. Since it may or may not lye the host bacterium it is considered more temperate in its action.

prophage

A bacteriophage that has integrates into the chromosome of a host bacterium

lysogen

A bacterium containing a prophage

microconidia

A conidium of the smaller of two types produced by the same fungal species and often differing in shape

macroconidia

A large usually multinucleate conidium of a fungus

chronic viral infection

In the case of chronic virus infections, the virus can be demonstrated in the body at all times and the disease may be present or absent for an extended period of time. Examples include hepatitis B (caused by HBV) and hepatitis C (caused by HCV).

provirus

An animal virus that has inserted its DNA into the chromosomes of its host cell. During its life cycle, HIV becomes this. For example, viral and/or host miRNAs may bind to certain viral messenger RNA (mRNA) molecules and block translation of viral proteins required for rapid viral replication, or they may bind to the mRNA of human genes that produce proteins used in viral replication. The resulting low viral levels may then minimize immune responses against that virus. In addition, these miRNAs may directly affect host immune defenses by turning off the production of antiviral cytokines or by blocking apoptosis of infected host cells. Examples include the herpesviruses, retroviruses, and anelloviruses.

Briefly describe at least 4 ways viruses can damage infected host cells.

Animal viruses may cause cytopathic effect or CPE that damages infected host cells in a variety of means, including: 1. Inhibiting normal host cell DNA, RNA, or protein synthesis. This can cause structural or functional defects in the infected host cell leading to cytolysis or altered cell functions. 2. Causing nicks or breaks in the host cell's chromosomes, as seen in congenital rubella syndrome. 3. Viral proteins and glycoproteins changing the antigenic surface of the host cell's cytoplasmic membrane resulting in its being recognized as foreign and destroyed by the body's immune defenses 4. Depleting the host cell of cellular materials essential for life or normal function. 5. Stimulating body cells to release inflammatory cytokines and chemokines. 6. Stimulating body cells to release inflammatory vasoactive peptides, bradykinins, histamines, etc. resulting in vasodilation and increased mucous secretion. 7.Inducing adjacent host cells to fuse together forming giant multinucleated cells or syncytias (see Slideshow Figs. 3A, 3B, 3C, and 3D) as seen with cytomegalovirus (CMV), varicella-zoster virus (VZV), and HIV. 8. Playing a role in normal cells becoming malignant (cell transformation by oncogenic viruses). 9. Causing cytolysis of the infected host cell

7. Reinfection

As many as 10,000 to 50,000 animal viruses may be produced by a single infected host cell.

E. HIV-1 viral assembly or maturation within the host cell and release from the host cell

Assembly of HIV virions begins at the plasma membrane of the host cell. Maturation occurs either during the budding of the virion from the host cell or after its release from the cell. Prior to budding, the Env polyprotein (gp160) goes through the endoplasmic reticulum and is transported to the Golgi complex where it is cleaved by a protease (proteinase) and processed into the two HIV envelope glycoproteins gp41 and gp120. These are transported to the plasma membrane of the host cell where gp41 anchors the gp120 to the membrane of the infected cell. The Gag (p55) and Gag-Pol (p160) polyproteins also associate with the inner surface of the plasma membrane along with the HIV genomic RNA as the forming virion begins to bud from the host cell. During maturation, HIV proteases (proteinases) will cleave the remaining polyproteins into individual functional HIV proteins and enzymes such as matrix proteins (MA; p17), capsid proteins (CA; p24), reverse transcriptase molecules (RT; p66/p51), and integrase molecules (IN; p32). a. The Gag polyproteins (p55) will be cleaved by HIV proteases to become HIV matrix proteins (MA; p17), capsid proteins (CA; p24), and nucleocapsid proteins (NC, p7 and p6). b. The Gag-Pol polyproteins (p160) will be cleaved by HIV proteases to become HIV matrix proteins (MA; p17), capsid proteins (CA; p24), proteinase molecules (protease or PR; p10), reverse transcriptase molecules (RT; p66/p51), and integrase molecules (IN; p32). The various structural components then assemble to produce a mature HIV virion.

lytic bacteriophage

Bacteriophage that replicate by way of the lyric life cycle, so named because they lye the host bacterium as a normal part of their life cycle. In the latter case, the cycle begins by the bacteriophage adsorbing to the host bacterium or lysogen and injecting its genome as in the lytic life cycle. However, the bacteriophage does not shut down the host cell. Instead, the bacteriophage DNA inserts or integrates into the host bacterium's DNA. At this stage the virus is called a prophage. Expression of the bacteriophage genes controlling bacteriophage replication is blocked by a repressor protein, and the phage DNA replicates as a part of the bacterium's DNA so that every daughter bacterium now contains the prophage. The number of viruses infecting the bacterium as well as the physiological state of the bacterium appear to determine whether the temperate bacteriophage enters the lytic cycle or becomes a prophage. In about one out of every million to one out of every billion bacteria containing a prophage, spontaneous induction occurs. The bacteriophage genes are activated and new bacteriophages are produced by the lytic life cycle

State why some bacteriophages are more complex than typical polyhedral or helical viruses.

Bacteriophages are viruses that only infect bacteria. Some bacteriophages are structurally much more complex than typical nucleocapsid or enveloped viruses and may possess a unique tail structure composed of a base plate, tail fibers, and a contractile sheath. Other bacteriophages, however, are simple icosahedrals or helical

Describe the lysogenic life cycle of temperate phages (including spontaneous induction).

Bacteriophages capable of a lysogenic life cycle are termed temperate bacteriophages. When a temperate bacteriophage infects a bacterium, it can either replicate by means of the lytic life cycle and cause lysis of the host bacterium, or, it can incorporate its DNA into the bacterium's DNA and become a noninfectious prophage

State 2 living and 2 nonliving characteristics of viruses.

a. Living characteristics of viruses 1. They reproduce at a fantastic rate, but only in living host cells. 2. They can mutate. b. Nonliving characteristics of viruses 1. They are acellular, that is, they contain no cytoplasm or cellular organelles. 2. They carry out no metabolism on their own and must replicate using the host cell's metabolic machinery. In other words, viruses don't grow and divide. Instead, new viral components are synthesized and assembled within the infected host cell. 3. The vast majority of viruses possess either DNA or RNA but not both.

Name 3 potentially pathogenic yeasts and state an infection each causes.

Candida can cause a variety of opportunistic infections in people who are debilitated, immunosuppressed, or have received prolonged antibacterial therapy. Women who are diabetic, pregnant, taking oral contraceptives, or having menopause are also more prone to vaginitis. These conditions alter the sugar concentration and pH of the vagina making it more favorable for the growth of Candida. People who are immunosuppressed frequently develop thrush, vaginitis, and sometimes disseminated infections. Any Candida infection is called candidiasis. Candida most commonly causes vaginitis, thrush (an infection of the mouth), balantitis (an infection of the foreskin and head of the penis), onychomycosis (a fungal infection of the nails), and dermatitis (diaper rash and other infections of moist skin). Less commonly, Candida can infect the lungs, blood, heart, and meninges, especially in the compromised or immunosuppressed host. Candida now causes about 10% of all cases of septicemia. Candidiasis of the esophagus, trachea, bronchi, or lungs, in conjunction with a positive HIV antibody test, is one of the indicator diseases for AIDS. Cryptococcus infections are usually mild or subclinical but, when symptomatic, usually begin in the lungs after inhalation of the yeast in dried bird feces. It is typically associated with with pigeon and chicken droppings and soil contaminated with these droppings. Cryptococcus, found in soil, actively grows in the bird feces but does not grow in the bird itself. Usually the infection does not proceed beyond this pulmonary stage. Any disease by this yeast is usually called cryptococcosis. Dissemination of the pulmonary infection can result in a very severe and often fatal cryptococcal meningoencephalitis. Cutaneous and visceral infections are also found. Although exposure to the organism is probably common, large outbreaks are rare, indicating that an immunosuppressed host is usually required for the development of severe disease. Extrapulmonary cryptococcosis, in conjunction with a positive HIV antibody test, is another indicator disease for AIDS. Pneumocystis jiroveci (formerly called Pneumocystis carinii) is thought to be transmitted from person to person by the respiratory route and is almost always asymptomatic. However, in persons with highly depressed immune responses, such as people with leukemias or infected with the Human Immunodeficiency Virus (HIV), P. jiroveci can cause a severe pneumonia called PCP (Pneumocystis pneumonia).

early or acute HIV infection

During early or acute HIV infection the virus primarily infects and destroys memory T4-lymphocytes which express the chemokine receptor CCR5 and are very abundant in mucosal lymphoid tissues. Here HIV also encounters the dendritic cells located throughout the epithelium of the skin and the mucous membranes where in their immature form called Langerhans cells they are attached by long cytoplasmic processes. The envelope glycoproteins gp41 and gp120 of HIV contain mannose-rich glycans that bind to mannan-binding proteins (pattern recognition receptors; also called lectin receptors) on the dendritic cells. Upon capturing antigens through pinocytosis and phagocytosis and becoming activated by pro-inflammatory cytokines, the dendritic cells detach from the epithelium, enter lymph vessels, and are carried to regional lymph nodes. By the time they enter the lymph nodes, the dendritic cells have matured and are now able to present antigens of HIV to naive T-lymphocytes located in the the lymph nodes in order to induce adaptive immune responses.

5. Viral Assembly or Maturation within the Host Cell

During maturation , the capsid is assembled around the viral genome. During enveloped virus maturation, envelope glycoproteins are transported to the cytoplasmic membrane of the host cell and the capsid assembles around the viral genome. During naked virus maturation, the capsid assembles around the viral genome.

chronic HIV infection

During the chronic phase of HIV infection, the lymph nodes and the spleen become sites for continuous viral replication and host cell destruction. During most of this phase, the immune system remains active and competent and there are few clinical symptoms. A steady state-infection generally persists where T4-lymphocyte death and T4-lymphocyte replacement by the body are in equilibrium. In a person infected with HIV, somewhere between one and two billion of these T4-cells die each day as a result of HIV infection and must be replaced by the body's lymphopoietic system in the bone marrow. It is estimated that 10 billion virions are produced and cleared in an infected individual each day. However, the enormous turnover of T4-lymphocytes eventually exhausts the lymphopoietic system and it becomes unable to replace the T4-cells being destroyed. A variety of mechanisms then eventually lead to immunodeficiency.

C. HIV-1 viral movement to the site of replication within the host cell and production of a provirus.

During uncoating, the single-stranded RNA genomes within the core or capsid of the virus are released into the cytoplasm. HIV now uses the enzyme reverse transcriptase, associated with the viral RNA genome, to make a DNA copy of the RNA genome. (Normal transcription in nature is when the DNA genome is transcribed into mRNA which is then translated into protein. In HIV reverse transcription, RNA is reverse-transcribed into DNA.) Reverse transcriptase has three enzyme activities: a. It has RNA-dependent DNA polymerase activity that copies the viral (+) RNA into a (-) viral complementary DNA (cDNA); b. It has ribonuclease activity that degrades the viral RNA during the synthesis of cDNA; and c. It has DNA-dependent DNA polymerase activity that copies the (-) cDNA strand into a (+) DNA to form a double-stranded DNA intermediate. As the cDNA is being synthesized off of the RNA template the ribonuclease activity degrades the viral RNA genome. The reverse transcriptase then makes a complementary DNA strand to form a double-stranded viral DNA intermediate A viral enzyme called integrase then binds to the double-stranded viral DNA intermediate, transports it theough the pores of the host cell's nuclear membrane, and inserts it into one of the host cell's chromosomes to form a provirus After integration, the HIV proviral DNA can exist in either a latent or productive state, which is determined by genetic factors of the viral strain, the type of cell infected, and the production of specific host cell proteins. The majority of the proviral DNA is integrated into the chromosomes of activated T4-lymphocytes. These generally comprise between 93% and 95% of infected cells and are productively infected, not latently infected. However, a small percentage of HIV-infected memory T4-lymphocytes persists in a resting state because of a latent provirus. These, along with infected monocytes, macrophages, and dendritic cells, provide stable reservoirs of HIV capable of escaping host defenses and antiretroviral chemotherapy.

entry inhibitors

EIs are agents interfering with the entry of HIV-1 into cells. During the adsorption and penetration stages of the life cycle of HIV, a portion or domain of the HIV surface glycoprotein gp120 binds to a CD4 molecule on the host cell. This induces a change in shape that brings the chemokine receptor binding domains of the gp120 into proximity with the host cell chemokine receptor. This brings about another conformational change that exposes a previously buried portion of the transmembrane glycoprotein gp41 that enables the viral envelope to fuse with the host cell membrane. EIs interfere with various stages of this process.

2. Viral Entry into the Host Cell

Enveloped viruses enter the host cell in one of two ways: 1. In some cases, the viral envelope may fuse with the host cell cytoplasmic membrane and the nucleocapsid is released into the cytoplasm 2. Usually they enter by endocytosis, whereby the host cell cytoplasmic membrane invaginates and pinches off, placing the virus in an endocytic vehicle Naked viruses enter the cell in one of two ways: 1. In some cases, interaction between the viral capsid and the host cell cytoplasmic membrane causes a rearrangement of capsid proteins allowing the viral nucleic acid to pass through the membrane into the cytoplasm 2. Most naked viruses enter by receptor-mediated endocytosis whereby the host cell cytoplasmic membrane invaginates and pinches off, placing the virus in an endocytic vesicle

e. nevirapine, delavirdine, and efavirenz

HIV Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

f. saquinavir, ritonavir, idinavir, nelfinavir, amprenavir, atazanavir, fosamprenavir, ritonavir

HIV Protease Inhibitors (PIs)

d. AZT (ZDV), didanosine, zalcitabine, stavudine, lamivudine, emtricitabine, tenofovir, and abacavir

HIV; nucleoside reverse transcriptase inhibitors

hyphae

branching tubular structure approximately 2-10 µm in diameter which is usually divided into cell-like units by crosswalls called septa

protease inhibitors

In order for maturation of HIV to occur, a HIV enzyme termed a protease has to cleave a long HIV-encoded gag-pol polyprotein to produce reverse transcriptase and integrase (coded by the HIV pol gene) and gag polyprotein (coded by the HIV gag gene). The HIV protease then cleaves the gag polyprotein into capsid protein p17, matrix protein p24, and nucleocapsid protein p7, as well as proteins p6, p2, and p1 whose functions are not yet fully understood (see Figs. 4A, 4B, and 4C). Proteases also cleave the env-polyprotein (coded by the HIV env gene) into the envelope glycprroteins gp120 and gp41 (see Fig. 5). Protease inhibitors are drugs that bind to the active site of this HIV-encoded protease and prevent it from cleaving the long gag-pol polyprotein and the gag polyprotein into essential proteins essential to the structure of HIV and to RNA packaging within its nucleocapsid (see 4C). As a result, viral maturation does not occur and noninfectious viral particles are produced.

Name 3 types of cells HIV primarily infects and briefly explain why

In order to infect a human cell an envelope glycoprotein on the surface of HIV called gp120 must adsorbs to both a CD4 molecule and then a chemokine receptor found on the surface of only certain types of certain human cells. 1. T4-helper lymphocytes (also called T4-cells and CD4+ cells) 2. monocytes 3. macrophages 4. dendritic cells

nucleoside reverse transcriptase inhibitors

In order to replicate, HIV uses the enzyme reverse transcriptase to make a DNA copy of its RNA genome. A complementary copy of this DNA is then made to produce a double-stranded DNA intermediate which is able to insert into host cell chromosomes to form a provirus. Most reverse transcriptase inhibitors are nucleoside analogs. A nucleoside is part of the building block of DNA, consisting of a nitrogenous base bound to the sugar deoxyribose but no phosphate group. A nucleoside analog chemically resembles a normal nucleoside. Once phosphate groups are added by either viral or host cell enzymes, the drugs now chemically resemble normal DNA nucleotides , the building block molecules for DNA synthesis. The nucleotide analog binds to the active site of the reverse transcriptase which, in turn, inserts it into the growing DNA strand in place of a normal nucleotide. Once inserted, however, new DNA nucleotides are unable to attach to the drug and DNA synthesis is stopped. This results in an incomplete provirus

Name 3 herpes viruses that may have a latent cycle, state in what cell types they become latent, and name the diseases each cause.

Herpes viruses, for example, are often latent in some cell types but productive in others. Herpes viruses include herpes simplex type 1 (HSV-1) which usually causes fever blisters or oral herpes, herpes simplex type 2 (HSV-2) which usually causes genital herpes, Epstein-Barr virus (EBV) which causes infectious mononucleosis and plays a role in certain cancers, varicella-zoster virus (VZV) which causes chickenpox and shingles, and cytomegalovirus (CMV) which causes a variety of infections in immunosuppressed persons and is also a leading cause of birth defects. In the case of HSV-1, HSV-2, and VZV, primary infection causes the virus to replicate within epithelial cells. However, some of the viruses enter and migrate down neurons where they become latent in the body of sensory neurons. Subsequent activation of the latently infected neurons by a variety of extracellular stimuli enables the viruses to migrate back up the nerve cell and replicate again in the epithelial cells. Herpes viruses use both host and viral miRNAs to switch between the productive life cycle in infected epithelial cells whereby large numbers of viruses are produced and the infected host cells are killed (as in the case of fever blisters) and the persistent latent state in nerve cells where low levels of viruses are produced and the infected host cells are not killed by apoptosis. With EBV, the virus is productive in epithelial cells but latent in B-lymphocytes.

latent viral infection

In a latent viral infection the virus remains in equilibrium with the host for long periods of time before symptoms again appear, but the actual viruses cannot be detected until reactivation of the disease occurs. Examples include infections caused by HSV-1 (fever blisters), HSV-2 (genital herpes), and VZV (chickenpox-shingles).

3. Viral Movement to the Site of Replication within the Host Cell and Release of the Viral Genome from the Remainder of the Virus.

In the case of viruses that enter by endocytosis, the endocytic vesicles containing the virus move within the host cell. During this process the pH of the endocytic vesicle typically decreases and this enables the virus to leave the endocytic vesicle. Viruses exit the endocytic vesicle through a variety of mechanisms, including: a. Fusion of the viral envelope with the membrane of the endocytic vesicle enabling the viral nucleocapsid to enter the cytoplasm of the host cell b. Lysis of the endocytic vesicle releasing the viral nucleocapsid into the cytoplasm of the host cell c. The viral capsid undergoing conformational changes that forms pores in the endocytic vesicle enabling the viral genome to enter the cytoplasm of the host cell In the case of most viruses with a DNA genome, the viral genome enters the nucleus of the host cell through one the mechanisms shown below. Most larger DNA viruses use either a or b to enter the nucleus. Method c is used by some very small DNA whose capsid is small enough to be carried through the nuclear pores. a. The viral DNA genome is released from the capsid, enters the cytoplasm of the host cell, and subsequently enters the nucleus of the host cell through the pores in the nuclear membrane b. The capsid of the viruses interacts with the nuclear membrane of the host cell enabling the viral DNA genome to enter the nucleus of the host cell via the pores in the nuclear membrane c. The nucleocapsid of a small DNA virus enters the nucleus of the host cell and the capsid is subsequently removed releasing the viral DNA genome into the nucleoplasm

a. amantadine, rimantidine, zanamivar, and oseltamivir

Influenza infections

A. retrovirus HIV-1 viral attachment or adsorption to the host cell

Initially, HIV uses a cellular protein called cyclophilin that is a component of its envelope to bind a low affinity host cell receptor called heparin. This first interaction enables the virus to initially make contact with the host cell. In order to infect a human cell, however, an envelope glycoprotein on the surface of HIV called gp120 must adsorbs to both a CD4 molecule and then a chemokine receptor found on the surface of only certain types of certain human cells. 1. T4-helper lymphocytes (also called T4-cells and CD4+ cells) 2. monocytes 3. macrophages 4. dendritic cells Chemokines are cytokines that promote an inflammatory response by pulling white blood cells out of the blood vessels and into the tissue to fight infection. Different white blood cells have receptors on their surface for different chemokines. The chemokine receptors are now thought to determine the type of CD4+ cell HIV is able to infect. First, a portion or domain of the HIV surface glycoprotein gp120 binds to its primary receptor, a CD4 molecule on the host cell. This induces a change in shape that enables the chemokine receptor binding domains of the gp120 to interact with a host cell chemokine receptor. The chemokine receptor functions as the viral co-receptor. This interaction brings about another conformational change that exposes a previously buried portion of the transmembrane glycoprotein gp41 called the fusion peptide that enables the viral envelope to fuse with the host cell membrane Most strains of HIV are referred to as M-tropic or T-tropic. The gp120 of M-tropic HIV is able to adsorb to the CD4 molecules and the CCR5 chemokine receptors found on CD4+ macrophages, immature dendritic cells, and memory T4-lymphocytes. (M-tropic HIV are also called R5 viruses since they adsorb to the chemokine receptor CCR5.) M-tropic HIV require only low levels of CD4 molecules expressed on the surface of the host cell for infection. M-tropic HIV are thought to spread the infection. These strains appear to be slower-replicating and less virulent than the later T-tropic strains and do not cause the formation of syncytias. HIV initially replicates to high levels within macrophages without destroying them. (The T-tropic HIV, found later in HIV infection, are faster-replicating, more virulent, and lead to syncytia formation.) Later during the course of HIV infection, most of the viruses have mutated their gp120 to become T- tropic and infect primarily mature dendritic cells and T4-lymphocytes by way of CD4 and the CXCR4 co-receptors found on these cells.

Giardia lamblia

can cause a gastrointestinal infection called giardiasis. Cysts pass out of the intestines of the infected host and are ingested by the next host. It is transmitted by the fecal-oral route.

Cryptosporidium

an intracellular parasite that causes a gastrointestinal infection called cryptosporidiosis, although in people who are immunosuppressed it can also cause respiratory and gallbladder infections. It is transmitted by the fecal-oral route.

conidiospores

Mold spores borne externally on an aerial hyphae called a conidiophore

sporangiospores

Mold spores borne internally within a sac or sporangium on an aerial hyphae called a sporangiophore

arthrospores

Mold spores produced by the fragmentation of vegetative hyphae

nucleocapsid

Naked virus; lacks an envelope and consists of only a genome and capsid

6. Viral Release from the Host Cell

Naked viruses are predominantly released by host cell lysis. While some viruses are cytolytic and lyse the host cell more or less directly, in many cases it is the body's immune defenses that lyse the infected cell. With enveloped viruses, the host cell may or may not be lysed. The viruses obtain their envelopes from host cell membranes by budding. As mentioned above, prior to budding, viral proteins and glycoproteins are incorporated into the host cell's membranes. During budding the host cell membrane with incorporated viral proteins and glycoproteins evaginates and pinches off to form the viral envelope. Budding occurs either at the outer cytoplasmic membrane, the nuclear membrane, or at the membranes of the endoplasmic reticulim or the Golgi apparatus. 1. Viruses obtaining their envelope from the cytoplasmic membrane are released during the budding process 2. Viruses obtaining their envelopes from the membranes of the nucleus, the endoplasmic reticulum, or the Golgi apparatus are then released by exocytosis via transport vesicles

AIDS

Progression to AIDS is marked by a viral load that progressively increases in number while the immune system weakens as a result of the destruction of increasing numbers of T4-lymphocytes and the inability of the body to continually replace these destroyed cells. As will be seen in Unit 5, the loss of T4-helper lymphocytes leads to a marked decline in cells called cytotoxic T-lymphocytes (CTLs), the primary cells the body's immune responses use to destroy virus-infected cells. Once a person progresses to full-blown AIDS he or she becomes susceptible to a variety of opportunistic infections by: •bacteria such as Mycobacterium avium complex (MAC), Salmonella, and Nocardia; •protozoa such as Cryptosporidium and Toxoplasma; •viruses such as cytomegalovirus (CMV), herpes simplex viruses types 1 and 2 (HSV-1, HSV-2), and varicella zoster virus (VZV); •Candida, Cryptococcus, Coccidioides, Histoplasma, and Pneumocystis. There is also an increased incidence of tumors, such Epstein-Barr virus-associated B-cell lymphomas, other lymphomas, cervical cancer, and Kaposi's sarcoma. Wasting syndrome and encephalopathy are also common.

Regarding the naming of enzymes involved in the replication of viral nucleic acid, state what the "dependent" part of the name refers to and what the "polymerase" part of the name refers to.

Regarding the enzymes involved in nucleic acid replication, the "dependent" part of the name refers what type of nucleic acid is being copied. The "polymerase" part of the name refers what type of nucleic acid is being synthesized, eg, DNA-dependent RNA-polymerase would synthesize a strand of RNA complementary to a strand of DNA.

Describe how certain viruses may contribute to the development of tumors by altering proto-oncogenes or tumor-suppressor genes.

Some viruses can also play a role in converting normal host cells into tumor cells. These viruses are capable of viral transformation, that is, they transform normal cells into malignant cells. In fact, five viruses, hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), Epstein-Barr virus (EBV), and human T-lymphotropic virus type I (HTLV-I) are thought to contribute to over 15% of the world's cancers. Up to 80% of these human viral-associated cancers are cervical cancer (associated with HPV) and liver cancer (associated with HBV and HCV). The development of tumors is a multistep process depending on the accumulation of mutations altering a number of genes. The altered genes then function collectively to cause malignant growth. Proliferation of normal cells is regulated by growth-promoting proto-oncogenes and counterbalanced by growth-restricting tumor suppressor genes. Mutations that increase the activities of proto-oncogenes to create oncogenes and/or decrease the activities of tumor suppressor genes can lead to growth of tumors. It is now known that many tumors require both activation of oncogenes from proto-oncogenes and inactivation of tumor suppressor genes for their development.

Briefly describe 3 different ways antifungal chemotherapeutic agents may affect fungi and give an example of an antibiotic for each way.

Since fungal cells, unlike prokaryotic bacterial cells, are not that different from human cells, it is more difficult to find a chemotherapeutic agent that is selectively toxic for fungi, that is, will inhibit or kill fungal cells without also inhibiting or killing human cells. 1. One antibiotic, griseofulvin (Fulvicin, Grifulvin, Gris-PEG), interferes with nuclear division by preventing the aggregation of microtubules needed for mitosis in superficial mycelial fungi. It is used only for severe dermatophyte infections. 2. The antimetabolites trimethoprim + sulfomethoxazole , trimetrexate, atovaquone, and flucytosine interfere with normal nucleic acid synthesis. Trimethoprim/sulfomethoxazole (Septra, Bactrim), atovaquone (Mepron), and trimetrexate (Neutrexin) are used to treat Pneumocystis pneumonia. Flucytosine (Ancobon) is used for more serious Candida infections. 3. Polyene antibiotics such as amphotericin B, pimaricin, and nystatin are fungicidal drugs that bind to ergosterol in the fungal cytoplasmic membrane thus altering its structure and function and causing leakage of cellular needs. Nystatin (Mycostatin) is used to treat superficial Candida infections (thrush, vaginitis, cutaneous infections), amphotericin B (Abelcet, Fungizone) is used for systemic Candida infections, Cryptococcus infections, and dimorphic fungal infections. 4. The azole derivative antibiotics such as clotrimazole, miconazole, itraconazole, fluconazole, and ketoconazole, are fungistatic drugs used to treat many fungal infections. They interfere with ergosterol biosynthesis and thus alter the structure of the cytoplasmic membrane as well as the function of several membrane-bound enzymes like those involved in nutrient transport and chitin synthesis. 5. Echinocandins, including caspofungin (Cancidas) and micafungin (Mycamine) are intravenous antifungals that inhibits glucan synthesis in fungal cell walls. It is used in the treatment of candidemia , Candida intra-abdominal abscesses, peritonitis, esophageal candidiasis, and pleural space infections. 6. Naftifine (Naftin) and terbinafine (Lamisil) are allylamines that block synthesis of ergosterol as does the topical thiocarbonate tolnaftate. They are used to treat dermatophyte infections.

Discuss why bacteria can be cultivated on synthetic media such as nutrient broth whereas viruses cannot.

Since viruses lack metabolic machinery of their own and are totally dependent on their host cell for replication, they cannot be grown in synthetic culture media. Animal viruses are normally grown in animals, embryonated eggs, or in cell cultures where in animal host cells are grown in a synthetic medium and the viruses are then grown in these cells.

State why antibiotics are of no use against viruses and what we must rely on to control viruses.

Since viruses lack the structures and metabolic processes that are altered by common antibiotics, antibiotics are virtually useless in treating viral infections. To date, relatively few antiviral chemotherapeutic agents are available and used to treat just a few limited viruses. Most of the antiviral agents work by inhibiting viral DNA synthesis. These drugs chemically resemble normal DNA nucleosides, molecules containing deoxyribose and either adenine, guanine, cytosine, or thymine. Viral enzymes then add phosphate groups to these nucleoside analogs to form DNA nucleotide analogs. The DNA nucleotide analogs are then inserted into the growing viral DNA strand in place of a normal nucleotide. Once inserted, however, new nucleotides can't attach and DNA synthesis is stopped. They are selectively toxic because viral polymerases are more prone to incorporate nucleotide analogs into their nucleic acid than are host cell polymerases.

slow viral infection

Slow infections are ones in which the infectious agents gradually increase in number over a very long period of time during which no significant symptoms are seen. Examples include AIDS (caused by HIV-1 and HIV-2) and certain lentiviruses that cause tumors in animals. Although not viruses, prions also cause slow infections.

State the major difference between the productive life cycle of animal viruses and the latent life cycle.

Some animal viruses, such as the herpes viruses and a group of viruses known as the retroviruses, are able to remain latent within infected host cells for long periods of time without replicating or causing harm. Some of these viruses remain latent within the cytoplasm of the host cell while others are able to insert or integrate their DNA into the host cell's chromosomes.

late complication following an acute infection

Some persistent infections, the viruses are continually present in the body. include subacute sclerosing panencephalitis (SSPE) that can follow an acute measles infection and progressive encephalitis that can follow rubella.

protozoan cyst

The dormant, protective form of some protozoa. enable them to survive harsh environments. allow some pathogens to survive outside their host.

Describe the process of lysogenic conversion and give 2 examples of exotoxins that result from lysogenic conversion.

The added genetic information provided by the DNA of a prophage may enable a bacterium to possess new genetic traits. For example, some bacteria become virulent only when infected themselves with a specific temperate bacteriophage. The added genetic information of the prophage allows for coding of protein exotoxin or other virulence factors. The following bacterial exotoxins are a result of lysogenic conversion by a prophage: a. the diphtheria exotoxin of the bacterium Corynebacterium diphtheriae; b. the Streptococcal pyrogenic exotoxin (Spe) produced by rare invasive strains and scarlet fever strains of Streptococcus pyogenes; c. The neurotoxin produced by Clostridium botulinum; d. exfoliatin, an exotoxin that causes scalded skin syndrome, produced by Staphylococcus aureus; e. the cholera exotoxin produced by Vibrio cholerae; and f. the shiga toxins produced by E. coli O157:H7.

Describe how most animal viruses obtain their envelope.

The envelope is composed of phospholipids and glycoprotein and for most viruses, is derived from host cell membranes by a process called budding. The envelope may come from the host cell's nuclear membrane, vacuolar membranes (packaged by the Golgi apparatus), or outer cytoplasmic membrane.Although the envelope is usually of host cell origin, the virus does incorporate proteins of its own, often appearing as glycoprotein spikes, into the envelope. These glycoprotein spikes function in attaching the virus to receptors on susceptible host cells.

Name 3 viruses that have been implicated in human cancers

The hepatitis B virus (HBV) is a DNA virus that may potentially cause chronic hepatitis in those infected. There is a strong link between chronic infection with HBV and hepatocellular carcinoma, which typically appears after 30-50 years of chronic liver damage and liver cell replacement. Chronic carriers of HBV have a 300 times greater risk of eventually developing liver cancer. Around 90% of individuals infected at birth and 10% of individuals infected as adults become chronic carriers of HBV. There are about one million chronic carriers of HBV in the US. Worldwide, HBV is responsible for 60% of all liver cancer cases. The hepatitis C virus (HCV) is a RNA virus that may also cause chronic hepatitis in those infected. As with HBV, there is a strong link between chronic infection with HCV and liver cancer, typically appearing after 30-50 years of chronic liver damage and liver cell replacement. Around 85% of individuals infected with HCV become chronic carriers and there are approximately four million chronic carriers of HCV in the US. Worldwide, HCV is responsible for 22 % of all liver cancer cases. The human papilloma viruses (HPV) are responsible for warts. While warts are generally considered as benign tumors, some sexually-transmitted strains of HPV (HPV-16 and 18 are definitely carcinogenic in humans; HPV-31 and 33 are probably carcinogenic), have been implicated in cervical and vulvar cancer, rectal cancer, and squamous cell carcinoma of the penis. In these tumor cells the viral DNA is usually found integrated in host cell chromosomes. In the US, HPVs are associated with 82% of the deaths due to cervical cancer each year, as well as a million precancerous lesions. The Epstein-Barr virus (EBV), a herpes virus, normally causes benign proliferations such as infectious mononucleosis and hairy leukoplakia of the tongue. However, it can contribute to non-Hodgkin's lymphoma in AIDS patients and post-transplantation lymphoproliferative diseases, appears to be an essential factor for posterior nasopharyngeal cancer in some individuals, can be a co-factor for Burkitt's lymphoma, and contributes to smooth-muscle tumors in immunosuppressed children. The retrovirus human T-lymphotropic virus type I (HTLV-I) can induce a rare adult T-lymphocyte leukemia-lymphoma.

Briefly describe at least 3 different ways viruses can evade host immune defenses.

The influenza viruses undergo what is called antigenic drift and antigenic shift. •With antigenic drift, mutations cause a gradual change in the hemagglutinin antigen that adsorbs to receptors on host cells. •Antigenic shift is caused by a human influenza virus acquiring a new genome segment from an influenza virus capable of infecting other animals such as a ducks or swine. This new genome segment causes a major change in the hemagglutinin antigen. Antibodies made against the original human influenza virus can no longer bind to the new strain of virus or stick the virus to phagocytes •Likewise HIV, because of its high rate of mutation and its intracellular recombination with other strains of HIV, as mentioned earlier in this unit, prouces altered gp120 to which antibodies made against the earlier strains of HIV can no longer bind. •The hepatitis C virus (HCV) frequently through mutation produces viral varients ("escape mutants") to resist antibodies •Epstein-Barr virus (EBV) and cytomegalovirus (CMV) inhibit proteasomal activity so that viral proteins are not degraded into viral peptides •Herpes simplex viruses (HSV) can block the TAP transport of peptides into the endoplasmic reticulum •Numerous viruses, such as the cytomegalovirus (CMV) and adenoviruses can block the formation of MHC-I molecules by the infected cell. As a result, no viral peptide is displayed on the infected cell and the CTLs are no longer able to recognize that the cell is infected and kill it •Epstein-Barr virus (EBV) down regulates several host proteins involved in attaching viral epitopes to MHC-I molecules and displaying them on the host cell's surface •Adenoviruses and Epstein-Barr Virus (EBV) code for proteins that blocks apoptosis, the programmed cell suicide mechanism triggered by various defense mechanisms in order to destroy virus-infected cells •The cytomegalovirus (CMV) can also trigger its host cell to produce altered MHC-I molecules that are unable to bind viral epitopes, and, therefore, are not recognized by CTLs. However, NK cells are also unable to kill this infected cell because it is still displaying "MHC-I molecules" on its surface. •CMV also produces microRNAs (miRNAs), small non-coding RNA molecules that down-regulates the production of stress-induced proteins that the killer-activating receptor of NK cells first recognizes. The miRNAs do this by binding to the host cell's mRNA coding for stress-induced proteins (see Fig. 13). Without this binding there is no kill signal by the NK cell. 4. Some viruses cause infected host cells to secrete molecules that bind and tie up cytokines, preventing them from binding to normal cytokine receptors on host cells. •Poxviruses cause infected host cells to secrete molecules that bind interleukin-1 (IL-1) and interferon-gamma (IFN-gamma). •Cytomegaloviruses (CMV) cause infected host cells to secrete molecules that bind chemokines. 5. Some viruses suppress immunocompetent cells. •Epstein-Barr virus (EBV) produces a protein that is homologous to the cytokine interleukin-10 (IL-10). IL-10 inhibits the activation of dendritic cells and macrophages, antigen-presenting cells that are needed to present antigens to T-lymphocytes for their activation. EBV also produces microRNAs (miRNAs), small non-coding RNA molecules that inhibit an interferon response by infected cells. The miRNAs do this by binding to the host cell's mRNA coding for interferon (see Fig. 13). •The human immunodeficiency virus (HIV) infects immunocompetent dendritic cells and T4-lymphocytes leading to their death or disfunction. 6. Some viruses block apoptosis of infected host cells enabling the infected host cell to survive and produce new viruses. •Cytomegalovirus (CMV) and herpes simplex type 1 virus (HSV-1) produce microRNAs (miRNAs), small non-coding RNA molecules that block protein involved in apoptosis, a programmed cell suicide. The miRNAs do this by binding to the host cell's mRNA coding for apoptosis-inducing proteins

State the median incubation period for AIDS and, in terms of viral load, exhaustion of the lymphopoietic system, and immune responses, briefly describe what marks the progression to AIDS.

The median incubation period for AIDS is around 10 years.

eclipse period

The period during viral life cycle when no intact viruses can be seen inside the host cell.

vegetative mycelium

The portion of the mycelium that anchors the mold and absorbs nutrients

capsomere

The protein subunits forming a viral capsid

mycelium

The total mass of hyphae that constitutes a mold colony

D. HIV-1 viral replication within the host cell

The vast majority of T4-lymphocytes, which are productively infected, immediately begin producing new viruses. In the case of the small percentage of infected, resting memory T4-lymphocytes, before replication can occur, the HIV provirus must become activated. This is accomplished by such means as antigenic stimulation of the infected T4-lymphocytes or their activation by factors such as cytokines, endotoxins, and superantigens. Following activation of the provirus, molecules of (+) mRNA are transcribed off of the (-) proviral DNA strand by the enzyme RNA polymerase II. Once synthesized, HIV mRNA goes through the nuclear pores into the rough endoplasmic reticulum to the host cell's ribosomes where it is translated into HIV structural proteins, enzymes, glycoproteins, and regulatory proteins. A 9 kilobase mRNA is formed that is used for three viral functions: a. Synthesis of Gag polyproteins (p55). These polyproteins will eventually be cleaved by HIV proteases to become HIV matrix proteins (MA; p17), capsid proteins (CA; p24), and nucleocapsid proteins (NC, p7). b. Synthesis of Gag-Pol polyproteins (p160). These polyproteins will eventually be cleaved by HIV proteases to become HIV matrix proteins (MA; p17), capsid proteins (CA; p24), proteinase molecules (protease or PR; p10), reverse transcriptase molecules (RT; p66/p51), and integrase molecules (IN; p32). c. During maturation, these RNA molecules also become the genomes of new HIV virions. The 9kb mRNA can also be spliced to form a 4kb mRNA and a 2kb mRNA. The 4kb mRNA is used to: a. Synthesize the Env polyproteins (gp160). These polyproteins will eventually be cleaved by proteases to become HIV envelope glycoproteins gp120 and gp41. See Slideshow Figs. 11A and 11B. b. Synthesize 3 regulatory proteins called vif, vpr, and vpu. The 2kb mRNA is used to synthesize 3 regulatory proteins known as tat, rev, and naf.

trophozoite

The vegetative, reproductive, feeding form of a protozoan

4. Viral Replication within the Host Cell

The viral genome directs the host cell's metabolic machinery (ribosomes, tRNA, nutrients, energy, enzymes, etc.) to synthesize viral enzymes and viral parts. The viral genome has to both replicate itself and become transcribed into viral mRNA molecules. The viral mRNA can then be translated by the host cell's ribosomes into viral structural components and enzymes need for replication and assembly of the virus.

Briefly describe pseodohypae, hyphae, blastoconidia (blastospores), and chlamydoconidia (chlamydospores) and name a yeast producing these structures.

The yeast Candida is said to be dimorphic in that it can grow as an oval, budding yeast, but under certain culture conditions, the budding yeast may elongate and remain attached producing filament-like structures called pseudohyphae. C. albicans may also produce true hyphae similar to molds. In this case long, branching filaments lacking complete septa form. The pseudohyphae and hyphae help the yeast to invade deeper tissues after it colonizes the epithelium. Asexual spores called blastoconidia (blastospores) develop in clusters along the hyphae, often at the points of branching. Under certain growth conditions, thick-walled survival spores called chlamydoconidia (chlamydospores) may also form at the tips or as a part of the hyphae.

Briefly describe protozoa.

unicellular eukaryotic microorganisms lacking a cell wall and belonging to the Kingdom Protista. Although there are nearly 20,000 species of protozoa, relatively few cause disease. Most inhabit soil and water.

Define dermatophyte, list 2 genera of dermatophytes, and name 3 dermatophytic infections

a group of molds that cause superficial mycoses of the hair, skin, and nails and utilize the protein keratin, that is found in hair, skin, and nails, as a nitrogen and energy source. The three most common dermatophytes are Microsporum, Trichophyton, and Epidermophyton. tinea capitis (infection of the skin of the scalp, eyebrows, and eyelashes) tinea barbae (infection of the bearded areas of the face and neck) tinea faciei (infection of the skin of the face) tinea corporis (infection of the skin regions other than the scalp, groin, palms, and soles) tinea cruris (infection of the groin; jock itch) tinea unguium (onchomycosis; infection of the fingernails and toenails) tinea pedis (athlete's foot; infection of the soles of the feet and between the toes).

b. acyclovir, famciclovir, penciclovir, and valacyclovir

used against herpes simplex viruses (HSV) and also used against varicella zoster viruses (VZV)

State what criteria are used in viral classification.

Viruses are typically classified according to the type of genome they contain, the type of capsid they possess, and whether they are enveloped or naked. 1. single-stranded DNA; naked; polyhedral capsid •Viral family: Parvoviridae •Size: 18-25nm •Examples and diseases: parvoviruses (roseola, fetal death, gastroenteritis; some depend on coinfection with adenoviruses) 2. double-stranded, DNA; naked; polyhedral capsid •Viral family: Papovaviridae; circular dsDNA •Size: 40-57nm •Examples and diseases: human papilloma viruses (HPV; benign warts and genital warts; genital and rectal cancers) •Viral family: Adenoviridae; dsDNA •Size: 70-90nm •Examples and diseases: adenoviruses (respiratory infections, gastroenteritis, infectious pinkeye, rashes, meningoencephalitis) 3. double-stranded, circular DNA; enveloped; complex •Viral family: Poxviridae •Size: 200-350nm •Examples and diseases: smallpox virus (smallpox), vaccinia virus (cowpox), molluscipox virus (molluscum contagiosum-wartlike skin lesions) 4. double-stranded DNA; enveloped; polyhedral capsid •Viral family: Herpesviridae •Size: 150-200nm •Examples and diseases: herpes simplex 1 virus (HSV-1; most oral herpes; herpes simplex 2 virus (HSV-2; most genital herpes), herpes simplex 6 virus (HSV-6; roseola), varicella-zoster virus (VZV; chickenpox and shingles), Epstein-Barr virus (EBV; infectious mononucleosis and lymphomas), cytomegalovirus (CMV; birth defects and infections of a variety of body systems in immunosuppressed individuals) •Viral family: Hepadnaviridae •Size: 42nm •Examples and diseases: hepatitis B virus (HBV; hepatitis B and liver cancer) 5. (+)single-stranded RNA; naked; polyhedral capsid •Viral family: picornaviridae •Size: 28-30nm •Examples and diseases: enteroviruses (poliomyelitis), rhinoviruses (most frequent cause of the common cold), Noroviruses (gastroenteritis), echoviruses (meningitis), hepatitis A virus (HAV; hepatitis A) 6. (+)single-stranded RNA; enveloped; usually a polyhedral capsid •Viral family: Togaviridae •Size: 60-70nm •Examples and diseases: arboviruses (eastern equine encephalitis, western equine encephalitis), rubella virus (German measles) •Viral family: Flaviviridae •Size: 40-50nm •Examples and diseases: flaviviruses (yellow fever, dengue fever, St. Louis encephalitis), hepatitis C virus (HCV; hepatitis C) •Viral family: Coronaviridae •Size: 80-160nm •Examples and diseases: coronaviruses (upper respiratory infections and the common cold; SARS) 7. (-)single-stranded RNA; enveloped; pleomorphic •Viral family: Rhabdoviridae; bullet-shaped •Size: 70-189nm •Examples and diseases: rabies virus (rabies) •Viral family: Filoviridae; long and filamentous •Size: 80-14,000nm •Examples and diseases: Ebola virus, Marburg virus (hemorrhagic fevers) •Viral family: Paramyxoviridae; pleomorphic •Size: 150-300nm •Examples and diseases: paramyxoviruses (parainfluenza, mumps); measles virus (measles) 8. (-) strand; multiple strands of RNA; enveloped •Viral family: Orthomyxoviridae •Size: 80-200nm •Examples and diseases: influenza viruses A, B, and C (influenza) •Viral family: Bunyaviridae •Size: 90-120nm •Examples and diseases: California encephalitis virus (encephalitis); hantaviruses (Hantavirus pulmonary syndrome, Korean hemorrhagic fever) •Viral family: Arenaviridae •Size: 50-300nm •Examples and diseases: arenaviruses (lymphocytic choriomeningitis, hemorrhagic fevers) 9. produce DNA from (+) single-stranded RNA using reverse transcriptase; enveloped; bullet-shaped or polyhedral capsid •Viral family: Retroviridae •Size: 100-120nm •Examples and diseases: HIV-1 and HIV-2 (HIV infection/AIDS); HTLV-1 and HTLV-2 (T-cell leukemia) 10. dsRNA; naked; polyhedral capsid •Viral family: Reoviridae •Size: 60-80nm •Examples and diseases: reoviruses (mild respiratory infections, infant gastroenteritis); Colorado tick fever virus (Colorado tick fever)

Compare the size of most viruses to that of bacteria.

Viruses are usually much smaller than bacteria with the vast majority being submicroscopic. While most viruses range in size from 5 to 300 nanometers (nm), in recent years a number of giant viruses, including Mimiviruses and Pandoraviruses with a diameter of 0.4 micrometers (µm), have been identified

bacteriophage

Viruses that infect only bacteria

c. foscarnet, gancyclovir, cidofovir, valganciclovir, and fomivirsen

used in treating severe cytomegalovirus (CMV)

Acanthamoeba

can cause rare, but severe infections of the eye, skin, and central nervous system. Acanthamoeba keratitis is an infection of the eye that typically occurs in healthy persons and can result in blindness or permanent visual impairment. Granulomatous amebic encephalitis (GAE) is an infection of the brain and spinal cord typically occuring in persons with a compromised immune system. Acanthamoeba is found in soil, dust, and a variety of water sources including lakes, tap water, swimming pools, and heating and air conditioning units. It typically enters the eyes and most cases are associated with contact lens use, but it can also enter cuts or wounds and be inhaled.

Plasmodium species

cause malaria and are transmitted by the bite of an infected female Anopheles mosquito. They reproduces asexually by schizogony in human liver cells and red blood cells but also reproduce sexually by gametes in the mosquito. In the case of malaria caused by P. vivax and P. ovale, a dormant form or hypnozoite remains in the liver and may cause later relapses.

Trypanosoma brucei-gambiens

causes African sleeping sickness and is transmitted by the bite of an infected Tsetse fly. The disease primarily involves the lymphatic and nervous systems of humans.

Entamoeba histolytica

causes a gastrointestinal infection called amoebic dysentery . The organism produces protective cysts which pass out of the intestines of the infected host and are ingested by the next host. It is transmitted by the fecal-oral route.

Blastomyces dermatitidis

causes blastomycosis, a disease commonly found around the Great Lakes region and the Mississippi and Ohio River valleys. Infection can range from an asymptomatic, self-healing pulmonary infection to widely disseminated and potentially fatal disease. Pulmonary infection may be asymptomatic in nearly 50% of patients. Blastomyces dermatitidis can also sometimes infect the skin. Blastomyces dermatitidis produces a mycelium with small conidiospores and grows actively in bird droppings and contaminated soil. When spores are inhaled or enter breaks in the skin, they germinate and the fungus grows as a yeast. having a characteristic thick cell wall. It is diagnosed by culture and by biopsy examination.

Coccidioides immitis

causes coccidioidomycosis, a disease endemic to the southwestern United States. An estimated 100,000 infections occur annually in the United States, but one to two thirds of these cases are subclinical. The mold form of the fungus grows in arid soil and produces thick-walled, barrel-shaped asexual spores called arthrospores by a fragmentation of its vegetative hyphae. After inhalation, the arthrospores germinate and develop into endosporulating spherules in the terminal bronchioles of the lungs. The spherules reproduce by a process called endosporulation, where the spherule produces numerous endospores (yeast-like particles), ruptures, and releases viable endospores that develop into new spherules.

Histoplasma capsulatum

causes histoplasmosis, a disease commonly found in the Great Lakes region and the Mississippi and Ohio River valleys. Approximately 250,000 people are thought to be infected annually in the US, but clinical symptoms of histoplasmosis occur in less than 5% of the population. Most individuals with histoplasmosis are asymptomatic. Those who develop clinical symptoms are typically either immunocompromised or are exposed to a large quantity of fungal spores. The mold form of the fungus often grows in bird or bat droppings or soil contaminated with these droppings and produces large tuberculate macroconidia and small microconidia. Although birds cannot be infected by the fungus and do not transmit the disease, bird excretions contaminate the soil and enrich it for mycelial growth. Bats, however, can become infected and transmit histoplasmosis through their droppings. After inhalation of the fungal spores and their germination in the lungs, the fungus grows as a budding, encapsulated yeast

Define viroid and name an infection caused by a viroid.

even more simple than viruses. They are small, circular, single-stranded molecules of infectious RNA lacking even a protein coat. They are the cause of a few plant diseases such as potato spindle-tuber disease,cucumber pale fruit, citrus exocortis disease, and cadang-cadang (coconuts).

Define mycosis.

fungal infections

Describe what is meant by the term "dimorphic fungus", name 2 systemic infections caused by dimorphic fungi, and state how they are initially contracted.

fungi may exhibit two different growth forms. Outside the body they grow as a mold, producing hyphae and asexual reproductive spores, but in the body they grow in a non-mycelial yeast form. These infections appear as systemic mycoses and usually begin by inhaling spores from the mold form. After germination in the lungs, the fungus grows as a yeast . Factors such as body temperature, osmotic stress, oxidative stress, and certain human hormones activate a dimorphism-regulating histidine kinase enzyme in dimorphic molds, causing them to switch from their avirulent mold form to their more virulent yeast form.

Define prion and name 3 protein misfolding diseases that appear to be initiated by prions

infectious protein particles responsible for a group of transmissible and/or inherited neurodegenerative diseases including Creutzfeldt-Jakob disease, kuru, and Gerstmann-Straussler- syndrome in humans, as well as scrapie in sheep and goats, and bovine spongiform encephalopathy (mad cow disease) in cattle and in humans (where it is called new variant Creutzfeldt-Jakob disease humans). The infections are often referred to as transmissible spongiform encephalopathies.

Trichomonas vaginalis

infects the vagina and the male urinary tract causing an infection called genitourinary trichomoniasis. It does not produce a cysts stage and is usually transmitted by sexual contact.

Toxoplasma gondii

intracellular apicomplexan and causes toxoplasmosis (see the AIDS pathology tutorial at the University of Utah). It can infect most mammals and is contracted by inhaling or ingesting cysts from the feces of infected domestic cats, where the protozoa reproduce both asexually and sexually, or by ingesting raw meat of an infected animal. Toxoplasmosis is usually mild in people with normal immune responses but can infect the brain, heart, or lungs of people who are immunosuppressed. It can also be transmitted congenitally and infect the nervous system of the infected child

mold

multinucleated, filamentous fungi composed of hyphae; have typical eukaryotic structures; have a cell wall usually composed of chitin, sometimes cellulose, and occasionally both; are obligate aerobe; grow by elongation at apical tips of their hyphae and thus are able to penetrate the surfaces on which they begin growing

Balantidium coli

only pathogenic ciliate which causes a diarrhea-type infection called balantidiasis. Cysts pass out of the intestines of the infected host and are ingested by the next host. It is transmitted by the fecal-oral route.

capsid

or core, is a protein shell surrounding the genome and is usually composed of protein subunits called capsomeres

Name 3 groups of fungi.

yeasts, molds, and fleshy fungi

acute viral infection

relatively short duration with rapid recovery. Most viruses that infect humans, such as those that cause routine respiratory infections (e.g., cold viruses, influenza viruses) and gastrointestinal infections (e.g., Rotaviruses, Noroviruses), cause acute infections.

B. HIV-1 viral entry into the host cell

the binding of a portion or domain of the HIV surface glycoprotein gp120 to a CD4 molecule on the host cell induces a change in shape that brings the chemokine receptor binding domains of the gp120 into proximity with the host cell chemokine receptor. This, in turn, brings about a conformational change that exposes a previously buried portion of the transmembrane glycoprotein gp41 enabling the viral envelope to fuse with the host cell membrane. After fusion of the viral envelope with the host cell cytoplasmic membrane, the genome-containing protein core of the virus enters the host cell's cytoplasm. (Occasionally the virus enters by endocytosis, after which the viral envelope fuses with the endocytic vesicle releasing the genome-containing core into the cytoplasm.)

Viral Attachment or Adsorption to the Host Cell

the binding of attachment sites on the viral surface with receptor sites on the host cell cytoplasmic membrane. For a virus to infect a host cell, that cell must have receptors for the virus on its surface and also be capable of supporting viral replication. These host cell receptors are normal surface molecules involved in routine cellular function, but since a portion of a molecule on the viral surface resembles the chemical shape of the body's molecule that would normally bind to the receptor, the virus is able to attach to the host cell's surface. The first step in the productive life cycle of an enveloped/naked virus is adsorption. In a enveloped virus glycoproteins on the viral envelope absorb to complementary receptors on the host cell membrane while in a naked virus it is proteins in the viral capsid that bind.

aerial mycelium

the portion of the mycelium that produces asexual reproductive spores

g. telaprevir, boceprevir, simeprevir, sofosbuvir

treatment of chronic hepatitis C