Reovirus
Naked, dsRNA and linear- 10-12 segments Coltivirus – Colorado tick fever Rotavirus – #1 cause of fatal diarrhea in children. Less common due to vaccination.
Picornavirus
Naked, ⊕ ssRNA, linear PERCHPoliovirus – polio-Salk/Sabin vaccines – IPV/OPVEchovirus – aseptic meningitisRhinovirus – "common cold"Coxsackievirus – aseptic meningitis; herpangina (mouth blisters, fever); hand, foot, and mouth disease; myocarditis; pericarditis HAV - acute viral hepatitis - RNA is translated into 1 large polypeptide that is cleaved by proteases into functional viral proteins.
Hepevirus
Naked, ⊕ single stranded and linear HEV
Caliciviruses
Naked, ⊕ single-stranded and linear Norovirus – viral gastroenteritis with vomiting, watery diarrea.
Flavivirus
Enveloped, ⊕ single-stranded and linear HCVYellow fevera – Liver, kidney, heart, and GI (black vomit) damageDenguea – Break bone fever (rash, muscle and joint pain), reinfection can result in dengue hemorrhagic shockSt. Louis encephalitisaWest Nile virusa – meningoencephalitisZika virusa
Togavirus
Enveloped, ⊕ ssRNA and linear Rubella – German measles (erythematous rash begins on face, progresses to torso)Eastern and Western equine encephalitisaChikungunya virusa
Coronaviruses
Enveloped, ⊕ single-stranded and linear "Common cold", SARS, MERS
Orthomyxoviruses
Enveloped, Θ single-stranded and linear- 8 segments Influenza virus
Rhabdoviruses
Enveloped, Θ single-stranded and linear Rabies
Bunyaviruses
Enveloped, ⊝ single-stranded and circular RNA- 3 segments California encephalitisaSandfly/Rift Valley feversaCrimean-Congo hemorrhagic feveraHantavirus – transmission by rodent excrement, hemorrhagic fever, pneumonia
Rhinovirus
A picornavirus (naked, ⊕ ssRNA) - Cause of common cold- >100 serologic types- Acid labile – destroyed by stomach acid, therefore, does not infect the GI tract (unlike other picornaviruses)
Yellow fever virus
A flavivirus (enveloped, ⊕ ssRNA)- Arbovirus, transmitted by Aedes mosquito- Reservoir: Monkeys- Endemic in South America and Sub-Saharan Africa Symptoms:1. High fever, headaches, chills, aching back2. Easing of symptoms and decline in fever3. Hemorrhage, multiorgan dysfunction, black vomitus, severe jaundice Diagnosis:- May see Councilman bodies (eosinophilic apoptotic globules) on liver biopsy.- IgM antibodies, blood PCR in early illness - Live-attenuated vaccine
Rotavirus
A segmented dsRNA (reovirus). - Most important global cause of infantile gastroenteritis.- Major cause of acute diarrhea in the US during winter, especially in day care centers, kindergartens. - Villous destruction with atrophy leads to ↓ absorption of Na+ and loss of K+. CDC recommends routine vaccination of all infants except those with a history of intussusception or SCID.
Influenza virus
Orthomyxovirus (enveloped, ⊝ ssRNA with 8 segments)- Contain hemagglutinin (binds sialic acid and promotes viral entry)- Contain neuraminidase (promotes progeny virion release) - Patients at risk for bacterial superinfection, most commonly S aureus, S pneumonia, and H influenzae. - Reformulated vaccine ("flu shot") contains viral strains most likely to appear during the flu season, due to the virus' rapid genetic change.- Killed viral vaccine is most frequently used.- Live attenuated vaccine contains temperature-sensitive mutant that replicates in the nose but not in the lung; administered intranasally.
Rubella virus
Togavirus (enveloped, ⊕ ssRNA) Causes rubella, once known as German 3-day measles. Presentation:- Low-grade fever- Postauricular and nuchal lymphadenopathy- Arthralgias- Fine, maculopapular, confluent rash that starts on face and spreads centrifugally to involve trunk and extremities. Causes mild disease in children but serious congenital disease. Congenital rubella findings:- Cataracts- Deafness- Cardiac defects- "Blueberry muffin" appearance due to dermal extramedullary hematopoiesis - Live vaccine (with mumps and measles) at 12-15 months and again at 2 years old
Paramyxoviruses
Enveloped, ⊝ ssRNA, non-segmented Parainfluenza – croup (seal-like barking cough)Mumps, MeaslesRSV – bronchiolitis in babies - All contain surface F (fusion) protein, which causes respiratory epithelial cells to fuse and form multinucleated cells. - Palivizumab (monoclonal antibody against F protein) prevents pneumonia caused by RSV infection in premature infants.
Croup (acute laryngotracheobronchitis)
Caused by parainfluenza viruses, which are paramyxoviruses (enveloped, ⊝ ssRNA).- Peak incidence: 6 months to 3 years- Most common in fall and winter Virus membrane contains hemagglutinin (binds sialic acid and promotes viral entry) and neuraminidase (promotes progeny virion release) antigens. - Results in "seal-like" barking cough, hoarse voice, and inspiratory stridor.- Symptoms usually during the late evening/night.- Narrowing of upper trachea and subglottis leads to characteristic steeple sign on x-ray.- Severe croup can result in pulsus paradoxus 2° to upper airway obstruction.
Measles (rubeola) virus
Paramyxovirus (enveloped, ⊝ ssRNA) - Prodromal fever with cough, coryza (inflammation of nasal mucosal), conjunctivitis, light sensitivity- Eventually Koplik spots (bright red spots with blue-white center on buccal mucosa)- Followed 1-2 days later by a maculopapular rash that starts at the head/neck and spreads downward - Lymphadenitis with Warthin-Finkeldey giant cells (fused lymphocytes) in a background of paracortical hyperplasia. Possible sequelae:- SSPE (subacute sclerosing panencephalitis, occuring years later)- Encephalitis (1:2000)- Giant cell pneumonia (rare except in immunosuppressed) - Vitamin A supplementation can reduce morbidity and mortality from measles, particularly in malnourished children.
Mumps
Paramyxovirus (enveloped, ⊝ ssRNA)- Uncommon due to effectiveness of MMR vaccine Symptoms:- Parotitis- Orchitis (inflammation of testes)- Aseptic meningitis- Pancreatitis- Can cause sterility
Rabies virus
Rhabdovirus (bullet-shapped virus, enveloped, ⊝ ssRNA, helical)- Infection more commonly from bat, raccoon, and skunk bites (US) and dogs (worldwide).- Aerosol transmission (eg, bat caves) also possible. - Negri bodies commonly found in Purkinje cells of cerebellum and in hippocampal neurons.- Travels to the CNS by migrating in a retrograde fashion up nerve axons after binding to ACh receptors. - Long incubation period (weeks to months) before symptom onset. Progression of disease: fever, malaise → agitation, photophobia, hydrophobia, hypersalivation → paralysis, coma → death Postexposure prophylaxis is wound cleaning plus immunization with killed vacine and rabies immunoglobulin (= passive-active immunity).
Prions
- conversion of a α-helical protein termed prion protein (PrPc) to a β-pleated form (PrPsc), which is transmissible via CNS-related tissue (iatrogenic CJD) or food contaminated by BSE-infected animal products.- resistant to autoclaving- results in spongiforme encephalopathy, dementia, ataxia, death Creuzfeldt-Jakob disease: rapidly progressive dementia, myoclonias, triphasic EEG waves Bovine spongiform encephalopathy (BSE) - "mad cow disease" Kuru - acquired disease in tribal populations practicing human cannibalism
Poxvirus
Enveloped, dsDNA and linear (largest DNA virus) - Smallpox eradicated world wide by use of the live-attenuated vaccine- Cowpox ("milkmaid blisters")- Molluscum contagiosum – flesh-colored papule with central umbilication. Molluscum bodies in central caseous material (eosinophilic cytoplasmic inclusion bodies).
Hepadnavirus
Enveloped, partially dsDNA and circular HBV: - Acute or chronic hepatitis- Not a retrovirus but has reverse transcriptase
Adenovirus
Naked, dsDNA and linear - Febrile pharyngitis – sore throat- Acute hemorrhagic cystitis – mostly boys age 5-15- Pneumonia- Conjunctivitis – "pink eye"- Gastroenteritis- Myocarditis Prevention: live, non-attenuated vaccine in military recruits
Papillomavirus
Naked, dsDNA and circular HPV – warts (serotypes 1, 2, 6, 11), CIN, cervical cancer (most commonly 16, 18)- Infects basal layer of the skin and mucous membranes- Malignancy may result: E6 and E7 inhibit tumor-suppressor genes p53 and Rb, respectively. - HPV infects basal epithelial cells through small breaks in the skin or mucosal surfaces. It has a predilection for stratified squamous epithelium, which is found on the anal canal, vagina, cervix, true vocal cords in the respiratory tract. - Koilocyte cells (cells with perinuclear cytoplasm vacuolization and nuclear enlargement) in Pap smears
Parvovirus
Naked, ssDNA and linear (smallest DNA virus)- Attaches to P antigen on RBCs B19 virus - Aplastic crisis in sickle cell disease- "Slapped cheek" rash in children (erythema infectiosum, or fifth disease)- RBC destruction in fetus leads to hydrops fetalis and death- In adults leads to pure RBS aplasia and rheumatoid arthritis-like symptoms- Rash and arthralgias (adults predominantly) are due to immune complexes in the skin and joints
Polyomavirus
Naked, dsDNA and circular - JC virus – progressive multifocal leukoencephalopathy (PML) in HIV- BK virus – transplant patients, commonly targets kidney. Occurs in ~5% of all kidney transplants patients.
Herpes simplex virus-1
Enveloped, DS and linear Route: Respiratory secretions, saliva - Gingivostomatitis- Keratoconjunctivitis- Herpes labialis- Herpetic whitlow on finger- Temperal lobe encephalitis- Esophagitis- Erythema multiforme - Most common cause of sporadic encephalitis, can present as altered mental status, seizures, and aphasia
Herpes simplex virus-2
Enveloped, DS and linear Route: Sexual contact, perinatal - Herpes genitalis- Neonatal herpes - Viral meningitis more common with HSV-2 than with HSV-1. - Tzanck smear looks for multinucleated giant cells typical for infection.
Varicella-Zoster virus (HHV-3)
Enveloped, DS and linear Route: Respiratory secretions - Varicella-zoster (chickenpox, shingles), encephalitis, pneumonia- Most common complication of shingles is post-herpetic neuralgia. - Latent in dorsal root or trigeminal ganglia; CN V1 branch involvement can cause herpes zoster ophthalmicus.
Epstein-Barr virus (HHV-4)
Enveloped, DS and linear Route: Respiratory secretions, saliva; aka "kissing disease" Mononucleosis – fever, hepatosplenomegaly, pharyngitis, lymphadenopathy (especially posterior cervical nodes). Avoid contact sports until resolution due to risk of splenic rupture. - Associated with lymphomas (eg, endemic Burkitt lymphooma), nasopharyngeal carcinoma (especially Asian adults), lymphoproliferative disease in transplant patients. - Infects B cells through CD21.- Atypical lymphocytes on peripheral blood smear – not infected B cells but reactive cytotoxic T cells.- ⊕ Monospot test – heterophile antibodies detected by agglutination of sheep or horse RBCs.- Use of amoxicillin in mononucleosis can cause maculopapular rash.
Cytomegalovirus (HHV-5)
Enveloped, DS and linear Route: Congenital transfusion, sexual contact, saliva, urine, transplant- Uses integrins to cause infection - Mononucleosis (⊝ Monospot) in immunocompetent patients- Infection in immunocompromised patients, especially pneumonia in transplant patients- Esophagitis- AIDS retinitis: hemorrhage, cotton-wool exudates, vision loss- Congenital CMV - Infected cells have a characteristic "owl eye" inclusions.- Latent in mononuclear cells. Treatment: supportive for healthy patients; ganciclovir/foscarnet ± human immunoglobulin for immunocompromised
Human herpes viruses 6 and 7
Enveloped, DS and linear Route: Saliva Roseola infantum (exanthem subitum):- High fevers for several days- Can cause seizures- Followed by diffuse macular rash - HHV-7 – less common cause of roseola
Human herpesvirus 8
Enveloped, DS and linear Route: Sexual contactSite of latency: B cells, glandular epithelial cells Kaposi sarcoma (neoplasm of endothelial cells)- Seen in HIV/AIDS and transplant patients- Dark/violaceous plaques or nodules representing vascular proliferations - Can also affect GI and lungs.
RNA viruses
Reovirus (DS): Rotavirus - cause of fatal diarrhea in children Picornavirus- Poliovirus- Echovirus - aseptic meningitis- Rhinovirus - "common cold"- Coxsackievirus - aseptic meningitis; herpangina; hand, foot, and mouth disase; myocarditis- HAV - acute viral hepatitis Hepevirus: HEV Calicivirus: Norovirus - viral gastroenteritis Flavivirus- HCV- Yellow fever virus- Dengue- West Nile virus- Zika virus Togavirus: Rubella Retrovirus- HIV- HTLV Coronavirus: "Common cold" SARS, MARS Orthomyxovirus: Influenza virus Paramyxovirus- Parainfluenza - croup- RSV - bronchiolitis in babies- Measles, Mumps Rhabdovirus: Rabies Deltavirus: HDV
Ebola virus
Filovirus (enveloped, ⊝ ssRNA)- Transmission requires direct contact with bodily fluids, fomites (including dead bodies), bats or primates (apes/monkeys); high incidence of nosocomial infection.- Targets endothelial cells, phagocytes, hepatocytes - Incubation period up to 21 days Presentation:- Abrupt onset of flu-like symptoms- Diarrhea/vomiting- High fever- Myalgia- Can progress to DIC, hemorrhage, shock - Diagnosed with RT-PCR within 48h of symptom onset. - Supportive care, no definitive treatment. Strict isolation of infected individuals and barrier practices for health care workers are key to preventing transmission.- High mortality rate
Zika virus
Flavivirus (enveloped, ⊕ single-stranded)- Transmitted by Aedes mosquito.- Sexual or vertical transmission possible.- Outbreaks more common in tropical and subtropical climates. Presentation:- Conjunctivitis- Low-grade pyrexia- Itchy rash in 20% of cases- Can lead to congenital microcephaly or miscarriage if transmitted in utero. - Diagnose with RT-PCR or serology. - Supportive care, not definitive treatment.
Hepatitis serologic markers
Anti-HAV (IgM) – Best test to detect acute hepatitis A.Anti-HAV (IgG) – Indicates prior HAV infection and/or prior vaccination; protects against reinfectino. HBsAg – Indicates HBV infection.Anti-HBs – Indicates immunity due to vaccination or recovery from infection.HBcAg – Antigen associated with core of HBV.Anti-HBc – IgM = acute/recent infection, IgM anti-HBc may be the sole ⊕ marker of window period; IgG = prior exposure or chronic infection.HBeAg – Secreted by infected hepatocyte into circulation. Not part of mature HBV virion. Indicates active viral replication and therefore high transmissibility and poorer prognosis.Anti-HBe – Indicates low transmissibility.
HIV
Diploid genome (2 molecules of RNA). 3 structural genes:- env (gp120 and gp41): envelope glycoproteins→ gp120 – attachment to CD4+ T cell→ gp41 – fusion and entry- gag (p24 and p17): capsid and matrix proteins, respectively- pol: reverse transcriptase, aspartate protease, integrase - Reverse transcriptase synthesizes dsDNA from genomic RNA; dsDNA integrates into host genome. - Virus binds CD4 as well as coreceptor, either CCR5 on macrophages (early infection) or CXCR4 on T cells (late infection). Homozygous CCR5 mutation = immunityHeterozygous CCR5 mutation = slower course
HIV diagnosis
Presumptive diagnosis made with HIV-1/2 Ag/Ab immunoassays. - These immunoassays detect viral p24 Ag capsid protein and IgG Abs to HIV-1/2. Very high sensitivity/specificity.- ⊕ tests are confirmed with HIV-1/2 Ab-differentiation immunoassays which determine whether patient has HIV-1 or HIV-2. If inconclusive differentiation assay, an HIV-1 nucleic acid amplification test (NAAT) is performed.- if NAAT Θ, patient had false positive initial Ag/Ab immunoasay. - Viral load tests determine the amount of viral RNA in the plasma. High viral load associated with poor prognosis. Also use viral load to monitor effect of drug therapy.- Use HIV genotyping used to determine appropriate therapy. AIDS diagnosis ≤200 CD4+ cells/mm3 (normal 500-1500 cells/mm3).HIV ⊕ with AIDS defining condition or CD4+ percentage <14%.
Viral genetics
Recombination: Exchange of genes between 2 chromosomes by crossing over within regions of base sequence homology. Reassortment: When viruses with segmented genomes (eg, influenza virus) exchange genetic material. Has potential to cause antigenic shift. 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. Eg, hepatitis D virus requires the presence of replicating hepatitis B virus to supply HBsAg, the envelope protein for HDV. 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.
DNA virus characteristics
Are HHAPPPy viruses: Hepadna, Herpes, Adeno, Pox, Parvo, Papilloma, Polyoma. All DNA viruses have dsDNA except Parvoviridae (ssDNA). All are linear except papilloma and polyoma (circular, supercoiled) and hepadna (circular, incomplete). All are icosahedral except pox (complex). All replicate in the nucleus except pox (carries own DNA-dependent RNA polymerase).
RNA virus characteristics
All RNA viruses have ssRNA except Reoviridae (dsRNA). All replicate in the cytoplasm (except retrovirus and influenza virus). (+) stranded RNA viruses: I went to a retro (retrovirus) toga (togavirus) party, where I drank flavored (flavivirus) Corona (coronavirus) and ate hippie (hepevirus) California (calicivirus) pickles (picornavirus).
Viral envelopes
Generally, enveloped viruses acquire their envelopes from plasma membrane when they exit the cell. Exceptions include herpesviruses, which acquire their envelopes from nuclear membrane. Naked viruses include:- Papillomavirus- Adenovirus- Parvovirus- Polyomavius- Calcivirus- Picornavirus- Reovirus- Hepevirus
HSV identification
- 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. PCR of skin lesions is test of choice. - Intranuclear eosinophilic Cowdry A inclusions also seen with HSV-1, HSV-2, and VZV.
Receptors used by viruses
CMV – Integrins (heparan sulfate) EBV – CD21 HIV – CD4, CXCR4, CCR5 Parvovirus B19 – P antigen on RBCs Rabies – Nicotinic AChR Rhinovirus – ICAM-1
Retroviruses
Enveloped, ⊕ ssRNA- 2 copies- Have reverse transcriptase HTLV (icosahedral) – T-cell leukemiaHIV (complex and conical) – AIDS
Arenaviruses
Enveloped, ⊕ and ⊝ single stranded and circular RNA- 2 segments LCMV – lymphocytic choriomeningitis virusLassa fever encephalitis – spread by rodents
