FA Microbiology- Virology

What disease states are caused by EBV?

- *Mononucleosis* (fever, hepatosplenomegaly, pharyngitis, lymphadenopathy of posterior cerival nodes esp.) Transmitted by respiratory secretions and saliva ("kissing disease") - Associated with *lymphomas* (Burkitt) - Associated with *nasopharyngeal carcinoma* (esp. in Asia)

What disease states are caused by HHV-6/HHV-7?

- *Roseola* (high fevers for several days that can cause seizures, followed by diffuse macular rash); common childhood exanthem Transmitted by saliva

What disease states are caused by CMV?

- Congenital infection - Monospot (-) mononucleosis - Pneumonia - Retinitis Infected cells have *characteristic "owl's eye" inclusions*. Trasmitted congenitally, via transfusion, sexual contact, saliva, urine or transplant.

Coronaviruses

- Enveloped - (+) ssRNA, linear - Helical 1) Coronavirus- "common cold" 2) SARS

Flaviviruses

- Enveloped - (+) ssRNA, linear - Icosahedral 1) HCV- hepatitis C 2) Yellow fever 3) Dengue fever 4) St. Louis Encephalitis 5) West Nile virus 6) Zika virus 7) JEV- Japanese B encephalitis

Togaviruses

- Enveloped - (+) ssRNA, linear - Icosahedral 1) Rubella 2) Eastern equine encephalitis (EEEV) 2) Western equine encephalitis (WEEV)

Orthomyxoviruses

- Enveloped - (+) ssRNA, linear, *8 segments* - Helical 1) Influenza virus

Retroviruses

- Enveloped - (+) ssRNA, linear, 2 copies - HTLV is icosahedral - HIV is complex and conical - have reverse transcriptase 1) HTLV- T-cell leukemia 2) HIV

Delta virus

- Enveloped - (-) ssRNA, *circular* - Capsid symmetry unknown 1) HDV- hepatitis D virus; must coinfect with HBV

Arenaviruses

- Enveloped - (-) ssRNA, *circular, 2 segments* - Helical 1) LCMV- lymphocytic choriomeningitis virus 2) Lassa fever encephalitis (spread by rodents)

Bunyaviruses

- Enveloped - (-) ssRNA, *circular, 3 segments* - Helical 1) California encephalitis 2) Sandfly/Rift Valley fever 3) Crimean-Congo hemorrhagic fever 4) Hantavirus- hemorrhagic fever, pneumonia

Filoviruses

- Enveloped - (-) ssRNA, linear - Helical 1) Ebola hemorrhagic fever 2) Marburg hemorrhagic fever

Rhabdoviruses

- Enveloped - (-) ssRNA, linear - Helical 1) Rabies

Paramyxoviruses

- Enveloped - (-) ssRNA, linear, nonsegmented - Helical 1) Parainfluenza- "croup" 2) RSV- bronchiolitis in babies (Rx is Rivaribin) 3) Measles 4) Mumps

Poxvirus

- Enveloped - dsDNA, linear - largest DNA virus Causes: Smallpox- eradicated Cowpox Molluscum contagiosum

What disease states are caused by HSV-2?

- Herpes genitalis - Herpetic whitlow - Neonatal herpes Latent in sacral ganglia. Transmitted by sexual contact, perinatally.

What disease states are caused by HSV-1?

- Herpes labialis - Herpetic whitlow - Gingivostomatitis - Keratoconjunctivities - Temporal lob encephalitis (MC cause of sporadic encephalitis) Transmitted by respiratory secretions, saliva.

What disease states are caused by HHV-8?

- Kaposi sarcoma, a neoplasm of endothelial cells, seen in HIV/AIDS and transplant pts. Dark/violaceous nodules or plaques, representing *vascular proliferation*. Can also affect GI tract and lungs. Transmitted by sexual contact.

What are the characteristics of negative-stranded viruses?

- Must transcribe (-) strand to (+) strand. - Virion brings its own *RNA-dependent polymerase* Includes: *A*renaviruses, *B*unyaviruses, *P*aramyxoviruses, *O*rthomyxoviruses, *F*iloviruses and *R*habdoviruses "*A*lways *B*ring *P*olymerase *O*r *F*ail *R*eplication

Picornaviruses

- Naked - (+) ssRNA, linear - Icosahedral - RNA is translated into 1 large polypeptide that is cleaved by proteases into functional viral proteins. - Can cause aseptic (viral) meningitis (except rhinovirus and HAV). - All are *enteroviruses* (fecal-oral spread) except rhinovirus 1) *P*oliovirus- polio-Salk/Sabin vaccines (IPV/OPV) 2) *E*chovirus- aseptic meningitis 3) *R*hinovirus- "common cold" 4) *C*oxsackievirus- aseptic meningitis; herpangina (mouth blisters, fever); Hand Foot and Mouth disease; myocarditis; pericarditis 5) *H*AV- acute hepatitis A *PERCH*

Hepevirus

- Naked - (+) ssRNA, linear - Icosahedral 1) HEV- Hepatitis E virus

Caliciviruses

- Naked - (+) ssRNA, linear - Icosahedral 1) Noroviruses- viral gastroenteritis, "cruise ship diarrhea"

Reoviruses

- Naked - *dsRNA* (the only one), linear, 10-12 segments - Icosahedral (double) 1) Colitvirus- Colorado tick fever 2) Rotavirus- #1 cause of fatal diarrhea in children

What is rubella virus?

- Togavirus - Causes rubella, aka German measles, aka 3-day measles - Fever, postauricular and other lymphadenopathy, arthralgias and fine rash. - Mild disease in children, but serious congenital disease (TORCHeS infection). - Congenital rubella include "blueberry muffin" appearance, indicative of extramedullary hematopoiesis.

What disease states are caused by VZV?

- Varicella-zoster (chickenpox, shingles) - Encephalitis - Pneumonia Latent in DRG of trigeminal ganglia. MC complication of shingle is post-herpetic neuralgia. Transmitted by respiratory secretions.

Herpesviruses

- enveloped - dsDNA, linear Members: HSV-1, HSV-2, VZV (HHV-3), EBV (HHV-4), CMV (HHV-5), HHV-6, HHV-7, HHV-8

Hepadnavirus

- enveloped - partially dsDNA, circular - aka *Hepatitis B virus* - causes acute or chronic hepatitis B - not a retrovirus but it has reverse transcriptase

Papillomavirus

- naked - dsDNA, circular - aka *HPV* - warts --> types 1, 2, 6, 11 - CIN (cervical intraepithelial neoplasia) - cervical cancer --> types 16, 18

Polyomavirus

- naked - dsDNA, circular Causes: - JC Virus --> progressive multifocal leukoencephalopathy (PML) in HIV pts - BK virus --> transplant pts, commonly targets kidneys "JK = Junky Cerebrum, BK = bad kidney"

Adenovirus

- naked - dsDNA, linear Causes: - febrile pharyngitis (sore throat) - acute hemorrhagic cystitis - pneumonia -conjunctivitis ("pink eye")

Parvovirus

- naked - ssDNA, linear - smallest DNA virus Causes: *B19 virus*, aka Fifth's disease, aka erythema infectiosum -aplastic crisis in sickle cell disease -"slapped cheeks" rash in children -RBC destruction in fetus --> hydrops fetalis and death -in adults ---> pure RBC aplasia and RA-like symptoms

What are the characteristics of HIV?

-Diploid genome (2 molecules of RNA) -Retrovirus -Reverse transcriptase synthesizes dsDNA from genomic RNA -dsDNA integrates into host genome -Virus binds CD4 as well as a coreceptor, either CCR5 on macrophages (early infection) or CXCR4 on T cells (late infection)

What are the subunit vaccines?

-HBV (antigen = HBsAg) -HPV (types 6,11,16,18)

What are the features of live attenuated vaccines?

-Induce humoral and cell-mediated immunity but have reverted to virulence on rare occasions. -No boosters are needed -Dangerous to give to immunocompromised hosts or their close contacts -CAN be given to HIV pts who show no signs of immunodeficiency

What are the live attenuated vaccines?

-MMR -Smallpox -Yellow fever -Rotavirus -VZV - Sabin polio -Intranasal influenza

Which viruses are naked?

-Papillomavirus -Adenovirus -Parvovirus -Polyomavirus -Picornavirus -Calicivirus -Reovirus -Hepevirus

What are the killed vaccines?

-Rabies -Injected influenza -Salk Polio ("Sal*K*=*K*illed") -Hep A

What are the 3 structural genes of HIV and the proteins they code for?

1) *env* (gp120 and gp41) - formed from cleavage of gp160 to form envelope glycoproteins - gp120 = attachment to host CD4+ T cells - gp41 = fusion and entry 2) *gag* - p24 = capsid protein 3) *pol* - reverse transcriptase, aspartate protease, integrase

What serologic markers are present during the window period for HBV?

1) Anti-HBe 2) Anti-HBc IgM

What serologic markers are present in an individual who has been immunized against HBV?

1) Anti-HBs THAT'S ALL!

What serologic markers are present during HBV recovery?

1) Anti-HBs 2) Anti-HBe 3) Anti-HBc IgG

Which RNA viruses of arboviruses, meaning they are arthropod borne?

1) Coltivirus (a reovirus) 2) Yellow fever (flavivirus) 3) Dengue fever (flavivirus) 4) St. Louis encephalitis (flavivirus) 5) Japanese B encephalitis (flavivirus) 6) Zika virus (flavivirus) 7) West Nile (flavivirus) 8) EEEV (togavirus) 9) WEEV (togavirus) 10) California encephalitis (bunyavirus) 11) Sandfly/Rift Valley fever (bunyavirus) 12) Crimean-Congo hemorrhagic fever (bunyavirus)

What serologic markers are present during chronic HBV with low infectivity?

1) HBsAg 2) Anti-HBe 3) Anti-HBc IgG

What serologic markers are present during chronic HBV with high infectivity?

1) HBsAg 2) HBeAg 3) Anti-HBc IgG

What serologic markers are present during acute HBV?

1) HBsAg 2) HBeAg 3) Anti-HBc IgM

What are the DNA viruses?

1) Herpesviruses 2) Hepadnavirus 3) Adenovirus 4) Parvovirus 5) Papillomavirus 6) Polyomavirus 7) Poxvirus All the P's except Picorna and Paramyxoviruses All the H's except for Hepevirus

What are the characteristics of DNA viruses?

1) Members are *HHAPPPP*y -*H*epadna, *H*erpes, *A*deno, *P*ox, *P*arvo, *P*apilloma, *P*olyoma -all the "P" viruses, except Picorna and Paramyxo are DNA viruses 2) All have dsDNA except for Parvo (ssDNA, because it's so small) 3) All have linear genomes except for papilloma and polyoma (circular, supercoiled) and hepadna (circular, incomplete) 4) All are icosahedral except for *pox in a box* 5) All replicate in the nucleus except for pox (bc it carries it's own DNA-dependent RNA polymerase)

What are the RNA viruses?

1) Reoviruses 2) Picornaviruses 3) Hepevirus 4) Caliciviruses 5) Flaviviruses 6) Togaviruses 7) Retroviruses 8) Coronaviruses 9) Orthomyxoviruses 10) Paramyxoviruses 11) Rhabdoviruses 12) Arenaviruses 13) Bunyaviruses 14) Delta virus

What is yellow fever virus?

A *flavivirus*, which is an arbovirus, transmitted by *Aedes* mosquitoes. *Monkey or human reservoir.* Symptoms: high fever, *black vomitus*, *jaundice (yellow)*. May see *Councilman bodies* (eosinophilic apoptotic globules) on *liver biopsy*.

What is ebola virus?

A Filovirus that targets endothelial cells, phagocytes, hepatocytes. Presents with abrupt onset of flu-like symptoms, diarrhea, vomiting, high fever, myalgia --> progresses to DIC, diffuse hemorrhage, shock, death. No definitive treatment; high mortality rate. Supportive care. Early stages vaccine effective. Strict isolation of infected individuals with barrier practices. Transmission requires direct contact with bodily fluids OR fomites (including dead bodies). High incidence of nosocomial infection.

What is the mumps virus?

A paramyxovirus that causes mumps. Uncommon due to effectiveness of MMR vaccine. Symptoms: *P*arotitis, *O*rchitis, and aspectic *M*eningitis ("mumpa makes your parotid glands and testes as big as *POM*-poms") Can cause sterility, especially after puberty.

What is rhinovirus?

A picornavirus that causes the "common cold"; more than 100 serologic types (this is why we never gain immunity against colds. Nonenveloped RNA virus. *Acid labile* --> destroyed by stomach acid; therefore does not infect GI tract like the other picornaviruses (only picornavirus that is not an enterovirus).

What is HBeAg?

A second, different antigenic determinant in the HBV core. HBeAg indicates *active viral replication* and therefore *high transmissibility*.

What is croup?

Acute laryngotracheobronchitis. Caused by parainfluenza viruses which are paramyxoviruses. Results in "seal-like" barking cough and *inspiratory stridor*. Narrowing of upper trachea and subglottis leads to characteristic *steeple sign* on X-ray. Severe croup can result in *pulsus paradoxus secondary to upper airway obstruction*.

What are segmented viruses?

All are RNA viruses. Include *BOAR* = *B*unyaviruses, *O*rthomyxoviruses , *A*renaviruses, *R*eoviruses Recombination of segments is what can cause epidemics (ex. influenza)

Where do RNA viruses replicated?

All replicate in the cytoplasm, except for influenza and retroviruses.

Where do DNA viruses replicate?

All replicate in the nucleus, except for poxvirus.

What is anti-HBc?

Antibody against HBcAg IgM = acute/recent infection with HBV IgG = prior exposure or chronic infection (NOT vaccination) IgM anti-HBc may be the sole positive marker of infection during window period.

What is Anti-HBe?

Antibody against HBeAg. *Indicates low transmissibility*.

What is Anti-HBs?

Antibody against HBsAg. Indicated immunity to hepatitis B.

What is HBcAg?

Antigen associated with core of HBV. If a patient has this they have active infection

What is HBsAg?

Antigen found on surface of HBV. Indicates hepatitis B infection.

What are Koplik spots?

Bright red spots with blue-white center on buccal mucosa, that preced measles rash by 1-2 days.

What are the paramyxoviruses?

Cause disease in children. 1) Parainfluenza (croup); seal-like barking cough 2) RSV (bronchiolitis, pneumonia) 3) Mumps 4) Measles All contain *F (fusion) protein*, which causes respiratory cells to *fuse and form multinucleated cells*.

What is genetic drift/antigenic drift?

Causes *epidemics*. Minor (antigenic drift) changes based on random mutation in hemagglutinin or neuraminidase genes. How the flu strains change from season to season. "Sudden shift is more deadly than gradual drift"

What is genetic shift/antigenic shift?

Causes *pandemics*. Reassortment of viral genome segments, such as when segments of human flu A virus reassort with swine flu A virus. "Sudden shift is more deadly than gradual drift"

How do enveloped viruses acquire their envelope?

Enveloped viruses, except for herpesviruses, acquire their envelopes from the *plasma membrane of the host cell*. Herpesviruses, however, acquire their envelope from the *nuclear membrane of the host cell*.

What are the signs and symptoms of hepatitis viruses?

Episodes of fever, jaundice, elevated ALT and AST (except in neonates with perinatal transmission; their liver function and bilirubin levels are still good due to their weak immune response against the virus). May see *Councilman bodies* (eosinophilic apoptotic globules) on liver biopsy.

What is viral recombination?

Exchange of genes between 2 chromosomes by crossing over within regions of significant base sequence homology.

Which hepatitis viruses have fecal-oral transmission?

H*A*V and H*E*V "The *vowels* hit your *bowels*" Naked viruses do not rely on an envelope, so they are not destroyed by the gut.

Which DNA viruses are enveloped?

Herpesviruses, Hepadnavirus, Poxvirus

What is Anti-HAV IgG?

IgG antibody indicates *prior* hepatitis A infection and/or *prior HAV vaccination*. *Protects against reinfection*.

What is Anti-HAV IgM?

IgM antibody to hepatitis A virus. Best serologic marker to detect acute hepatitis A.

What is the function of DNA polymerase in HBV?

In HBV, DNA polymerase has both DNA- and RNA-dependent activities. Upon entry into the nucleus, the polymerase functions to complete the partial dsDNA. The host RNA polymerase transcribes mRNA from viral DNA to make viral proteins. The DNA polymerase then reverse transcribes viral RNA to DNA, which is the genome of the progeny virus.

What are the features of killed vaccines?

Induce on *humoral* immunity but carry no risk of reversion to virulence.

What is the immunologic basis of EBV mononucleosis?

Infects B cells through CD21. Atypical lymphocytes seen on peripheral blood smear are not infected B cells, but rather reactive cytotoxic T cells. Detected by Monospot test- heterophile antibodies detected by agglutination of sheep or horse RBCs.

For a virus to be an enterovirus, what characteristic must it have?

It must be *acid-stabile*; i.e. NOT destroyed by gastric juices. All picronaviruses are enteroviruses, except rhinoviruses, because they are heat-labile.

What is phenotypic mixing?

Occurs with simultaneous infection of a cell with 2 viruses. Genome of virus A can be partially or completely coated (forming pseudovirion) with the surface proteins of virus B. Type B protein coat determines the tropism (infectivity) of the hybrid virus. However, the progeny from this infection have a type A coat that is encoded by type A genetic material.

Which RNA viruses are naked?

Only Reoviruses, Picornaviruses, Hepevirus and Caliciviruses. Everything else has an envelope.

What are the characteristics of influenza viruses?

Orthomyxoviruses. Enveloped, (-) ssRNA viruses with 8-segment genome. Contain *hemagglutinin (promotes viral entry)* and *neuraminidase (promotes progeny virion release)* antigens. Pts at risk for fatal bacterial superinfection, most commonly S. aureus, S. pneumoniae, H. influenzae. Rapid changes due to recombination of segments. Pandemics due to antigenic shift with human and animal strains (H1N1).

All DNA viruses have linear genomes except which viruses?

Papillomavirus, Polyomavirus and Hepadnavirus. These all have circular DNA genomes.

All DNA viruses are dsDNA, except for which virus?

Parvoviridae (ssDNA) Parvus means small, so think about how small it is being the reason it can only carry ssDNA.

Which naked viral genomes are infective?

Purified nucleic acids of most dsDNA (except poxvirus and HBV), and (=) strand ssRNA (=mRNA) viruses are infectious. Naked nucleic acids of (-) strand ssRNA and dsRNA viruses are not infectious (they require polymerases contained in the complete virion).

What are the only times that anti-HBs serologic markers are present?

Recovery from HBV Immunized against HBV

What is the flu vaccine?

Reformulated vaccine ("flu shot") contains viral strains most likely to appear during the upcoming flu season. Killed viral vaccine is most frequently used. Live attenuated vaccine contains temperature-sensitive mutant that replicated in the nose, but not in the lung; administered to children intranasally. CDC no longer recommends its use, due to lack of evidence of effectiveness.

All RNA viruses are ssRNA except for which virus?

Reoviridae (dsDNA)

Which RNA viruses are positive-stranded?

Retrovirus Togavirus Flavivirus Coronavirus Hepevirus Calicivirus Picornavirus

What is the rabies virus?

Rhabdovirus, (-) ssRNA, enveloped, linear genome, helical capsid. *Bullet-shaped* virus. *Negri bodies* commonly found in *Purkinje cells of cerebellum and in hippocampal neurons*. Long incubation period (weeks to a year) before onset. Postexposure prophylaxis = wound cleaning + immunization with killed vaccine and rabies Ig. Example of passive-active immunity combo. Travels to CNS by migrating in retrograde fashion up nerve axons after binding to ACh receptors. Progression: fever, malaise --> agitation, photophobia, hydrophobia, hypersalivation --> paralysis, coma --> death. Only a handful of survivors. Most commonly from bat, raccoon and skunk bite in US.

What is rotavirus?

The most important and deadly cause of infantile gastroenteritis. A segmented dsRNA virus (reovirus). Major cause of acute diarrhea in US, during winter, especially in day car and kindergartens. Villous destruction with strophy leads to decreased absorption of Na+ and loss of K+. Routine vaccination of all infants (live, attenuated).

How is HSV identified?

Viral culture for skin/genitalia. CSF PCR for herpes encephalitis. Tzanck test- a smear of an opened skin vesicle to detect multinucleated giant cells commonly seen in HSV-1, HSV-2, and VZV infection. Intranuclear inclusions seen with HSV-1, HSV-2 and VZV. "Tzanck heavens I tested negative for herpes!"

What are the characteristics of Hepatitis B virus?

Virus: DNA hepadnavirus Transmission: Parenteral, sexual, perinatal Carrier: Yes Incubation: Long (months) HCC risk: Yes *B*lood, *B*aby-making, *B*irthing

What are the characteristics of Hepatitis D virus?

Virus: RNA delta virus, aka delta agent Transmission: Parenteral, sexual, perinatal Carrier: Yes Incubation: Superinfection (HDV after HBV) = short; Coinfection (HDV + HBV) = long HCC risk: Yes *D*efective virus is *D*ependent on HBV Superinfection gives a worse prognosis.

What are the characteristics of Hepatitis C virus?

Virus: RNA flavivirus Transmission: blood (IVDU, post-transfusion) Carrier: Yes Incubation: long HCC risk: Yes *C*hronic, *C*irrhosis, *C*arcinoma, *C*arrier

What are the characteristics of Hepatitis E virus?

Virus: RNA hepevirus Transmission: Fecal-oral, especially waterborne Carrier: No Incubation: Short HCC risk: No High mortality in pregnant women. *E*nteric, *E*xpectant mothers, *E*pidemic

What are the characteristics of Hepatitis A virus?

Virus: RNA picornavirus Transmission: Fecal-oral Carrier: No Incubation: Short (weeks) HCC risk: No *A*symptomatic, *A*cute, *A*lone (no carriers)

What is the role of Vitamin A in measles?

Vit A supplementation can reduce measles mortality in malnourished or vitamin-deficient children.

What is viral complementation?

When 1 of 2 viruses that infect the cell has a mutation that results in a nonfunctional protein. The nonmutated virus "complements" the mutated one by making a functional protein that serves both viruses. For example, hep D virus requires the presence of replicating hepatitis B virus to supply HBsAg, the envelope protein for hep D virus.

What is viral reassortment?

When viruses with segmented genomes (ex. influenza) exchange genetic material. For example, the 2009 novel H1N1 influenza virus A epidemic emerged via complex viral reassortment of genes from human, swine and avian viruses.

Are there vaccines against paramyxoviruses?

You betcha! 1) MMR- covers measles and mumps, plus rubella which is a togavirus. Live, attenuated. Repeat after me, "It does not cause autism!" 2) *Palivizumab*; trade name Synagis, (*monoclonal ab against F protein*, not "technically" a vaccine; induces passive immunity, not acitve); prevents pneumonia caused by RSV infection in premature infants. Must give multiple doses throughout the season. Insurance companies DO NOT want to pay for it...be ready for a fight!

What is the measles virus?

aka *rubeola*; paramyxovirus Prodromal fever with *cough, coryza, conjunctivitis, and Koplik spots*, followed by a 8maculopapular rash that starts at head/neck/forehead and spreads downward*. Lymphadenitis with *Warthin-Finkeldey giant cells (fused lymphocytes)* in a background of *paracortical hyperplasia*. SSPE, encephalitis and giant cell pneumonia are possible sequlae.