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141 Cards in this Set
- Front
- Back
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DNA Viruses
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Hepadnavirus *partially dsDNA
Herpesvirus Adenovirus Parvovirus *ssDNA Papillomavirus Polyomavirus Poxvirus *replicates in cytoplasm DNA viruses are HHAPPPPy viruses. |
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Naked DNA viruses
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Papillomaviridae
Adenoviridae Polyomaviridae Parvoviridae |
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Which DNA viruses replicate in the cytoplasm?
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Poxvirus - carries own DNA-dependent RNA polymerase for transcription and encodes its own replication enzymes
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Which DNA viruses replicate in the nucleus?
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Hepadenavirus
Herpesvirus Adenovirus Polyomavirus Papillomavirus Parvovirus |
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Which DNA virus is ssDNA?
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Parvovirus ("part-of-a-virus")
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Which DNA viruses are dsDNA?
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Hepadnavirus *but dsDNA!
Herpesvirus Adenovirus Polymavirus Poxvirus Papillomavirus |
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Which DNA viruses are circular?
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Papillomavirus
Polymoavirus Hepadnavirus |
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Which DNA viruses are linear?
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Herpesvirus
Poxvirus Adenovirus Parvovirus |
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Which DNA virus has complex symmetry?
What is the symmetry of the remaining DNA viruses? |
Poxvirus
Icosahedral symmetry |
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Poxvirus replication process
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1. Initial partial uncoating
2. Early, limited gene transcription --> early enzymes and proteins including uncoatase 3. Uncoatase triggers further uncoating and releases enzymes for DNA replication 4. Virally-encoded machinery replicates DNA 5. Late transcription --> structural proteins 6. Builds its own membrane around core factories --> inclusion bodies (Guarnieri bodies) 7. Additional "wrapping" from Golgi membranes 8. Release by lysis |
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Guarnieri bodies
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Inclusion bodies made of membrane + core viral particles of Poxvirus
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Uncoatase
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Poxvirus enzyme that removes core membrane to release enzymes for DNA replication
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Medically important Poxviridae members
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Variola virus (smallpox)
Vaccinia virus (cowpox) Molluscum Contagiosum virus |
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Clinical manifestation of variola virus
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Smallpox:
Vesicular rash in mouth Vesicular pustular rash on body (centrifugal distribution = extremities + face >> trunk) Vomiting, diarrhea, bleeding Toxemia + shock --> mortality (40%) |
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Transmission of variola virus
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Respiratory droplets (highly contagious!)
Stable envelope so transmitted via fomites, too. |
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Pathogenesis of variola virus/poxvirus
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Acquired via inhalation and infects respiratory epithelial cells. Virus multiplies in regional lymph nodes --> primary virema --> hemorrhage of small vessels of dermis leading to rash and "pox" + spread to spleen and liver --> secondary viremia --> disseminate to skin resulting in rash and pox
Cell-mediated immunity important for clearing infection. Humoral immunity protects against reinfection. Sebaceous glands susceptible to infection --> necrosis and edema Patients toxemic and dehydrated Immunocompromised patients --> hemorrhagic smallpox |
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Pathogenesis of Molluscum contagiousum virus
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Infects epidermal cells to form localized, fleshy lesion with umbilicated center. Due to epidermal localization, minimal inflammatory response.
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Diagonsis of Molluscum Contagiosum virus
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Molluscum bodies = eosinophilic cytoplasmic inclusions in biopsy of skin lesion.
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Diagnosis of variola virus
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PCR for viral DNA
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Virulence factors of Molluscum contagiousum virus
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EGF homolog --> hyperplasia
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Virulence factors of variola virus/poxvirus
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Chemokine + cytokine homologs antagonize normal immune function
Apoptosis inhibitors Interferon antagonists |
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Clinical manifestations of Molloscum contagiosum virus
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Nodular or wart-like lesions that begin as papules with central plug (umbilicated) that is readily expressed.
Common on trunk, genitalia, proximal extremities, occur in clusters. More common in children. |
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Treatment of smallpox
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Cidofovir (anti-viral Rx) inhibits smallpox DNA polymerase
Vaccina virus vaccine for smallpox (effective b/c only 1 serotype). |
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Transmission of molloscum contagiosum virus
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Direct contact (sexual) or fomites.
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Adenovirus replication
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1. Binds coxsackievirus and adenovirus receptor protein (CAR) on epithelial cells
2. Receptor-mediated endocytosis 3. Replicates in nucleus 4. Cellular RNA pol II transcribes E1A first 5. E1A binds RB to free E2F to begin G1 phase 6. E2B binds p53 to block apoptosis 7. E2 gene transcribes for DNA pol and ssDNA binding protein for genome replication 8. Late pre-mRNA has five potential poly A sites --> spliced --> 15 mRNAs enconding structural proteins 9. Capsids self-assemble in nucleus and DNA inserted 10. L3 protease cleaves proteins in capsid to make mature particle 11. Release by lysis |
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Clinical manifestations of adenovirus
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Typically affects young children
1. Acute febrile pharyngitis: flu-like sx + conjunctivitis 2. Pharyngoconjunctival fever: fever, conjunctivitis, pharyngitis (only virus that produces this constellation of sx!) Types 4 and 7 1. Acute respiratory disease: military; fever, cough, pharyngitis, cervical adenitis Types 40 - 42 1. Acute gastroenteritis and diarrhea Others 1. "Swimming pool" conjunctivitis 2. Epidemic keratoconjunctivitis: occupational hazard for industrial workers; corneal opacity that can last for years |
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Transmission of adenovirus
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Respiratory droplets, close contact, fecal-oral
Capsid resistant to inactivation May have asymptomatic shedding More prevalent in young kids |
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Adenovirus pathogenesis
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1. Infects epithelial cells of respiratory tract and intestinal tract
2. Direct cytotoxic damage 3. Virus may spread to lymph nodes and can persist as latent infection of tonsils and adenoids 4. Cleared by cell-mediated immunity, and type-specific, serum-neutralizing antibody provides long-term protection |
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Adenovirus virulence factors
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Infects mucoepithelial cells and causes direct cell damage.
Interferes with antigen presentation on MHC class I Blocks IFN antiviral response by preventing PKR activation Can cause latent infections in adenoids |
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Diagosis of adenoviris infection
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PCR or immunoassay
Can't culture serotype 40 - 42 |
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Treatment of adenovirus infection
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No specific treatment.
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Prevention of adenovirus
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Live oral vaccine for types 4 and 7 used in military recruits.
Hand-washing |
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Transmission of human papillomavirus
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Direct skin-to-skin contact transmits cutaneous HPV
Anogenital HPV can be transmitted sexually (includes non-penetrative sexual contact) Indirect contact with fomites |
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High-risk types and characteristics vs. low-risk oncogenic types and characteristics of genital HPV
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High-risk oncogenic HPV types = HPV 16 and 18 are closely linked with cervical cancer
1. high risk of malignancy 2. immortalization of keratinocytes 3. integrates into cellular DNA Low-risk oncogenic HPV types = 6 and 11 cause benign genital warts 1. low malignancy risk 2. no immortalization of keratinocytes 3. no integration into cellular DNA |
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Why are subtypes 16 and 18 transforming and subtypes 6 and 11 are not?
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Subtypes 16 and 18:
1. E6 binds p53 and targets it for ubiquitination and proteolysis 2. E7 sequesters Rb Subtypes 6 and 11 have E6 and E7 that do not bind p53 or Rb effectively |
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Why don't all women with subtypes 16 and 18 get cervical cancer?
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Chromosomal integration is key. If E2 inactivated (E2 = E6/E7 repressor), then E6 and E7 are expressed.
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What are E6 and E7 of HPV analagous to?
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E6 is analogous to E1B - both bind p53
E7 is analogous to E1A - both bind Rb |
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Clinical manifestations of HPV?
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Common warts (types 1, 2, 4)
Anogenital warts (types 6, 11) Anogenital cancer (types 16, 18) Epidermodysplasia verruciformis: immunodeficient patients have widespread, chronic cutaneous HPV lesions |
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Pathogenesis of HPV
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1. HPV targets basal epithelial cells, entry via cracks in skin or tears/lacerations in mucosal surface
2. Infection remains localized and may resolve spontaneously, remain latent, or (depending on type) progress to dysplasia and carcinoma. 3. HPV replication and virus production tied to squamous epithelial cell differentiation. 4. HPV DNA replicates in synchrony with basal stem cell DNA, but no capsid proteins made. 5. As epithelial cells mature, they become permissive --> capsid production, virion assembly, and viral particle production in terminally differentiated cells. (Replicate in basal layer and travel up to skin where viral particles shed in horny layer/stratum corneum.) 6. E6 (binds p53) and E7 (binds Rb) stimulate cell proliferation. 7. High-risk HPV types integrate into cellular DNA --> E6 and E7 genes intact --> continuous and increased expression of E6 and E7 --> cell cycle dysregulation --> malignant tumor phenotype 8. Infections eradicated and controlled by cell-mediated immunity. |
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HPV virulence factors
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HPV has capacity to establish latent infections. High-risk HPV types 16 and 18 can integrate in chromosomal DNA.
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Diagnosis of HPV
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Cervical lesions can be seen using acetic acid and magnification.
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Prevention of HPV
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Prophylactic vaccine Gardasil is active against types 16, 18, 6, 11
70% protection from cervical CA with HPV 16, 18. Protection against genital warts. |
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Medically important polyoma viruses
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Merkel cell polyoma virus
JC virus BK virus |
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What do all polyomaviruses produce and what is its role?
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Large T-antigen
Required for transcription and helicase activity; binds ORI to initiate replication Inactivate both Rb and p53 (does the work of both E6 and E7) --> transforming |
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Merkel cell polyoma virus
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Merkel cell carcinoma arises from neurosecretory cells in skin
Highly aggressive and malignant skin cancer, associated with UV exposure. Can chromosomally integrate --> disrupt helicase activity of T-antigen --> virus doesn't replicate + lyse, instead truncated T-antigen is made which can K.O. Rb and p53 so cell replicates |
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JC virus transmission
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Probably passed parent to infant
Found in GI tract and urothelial tissues so may be from contaminated food/water |
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JC virus clinical manifestations
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Progressive multifocal leukoencephalopathy (PML): JC virus in brain --> infection of oligodendrocytes --> demyelination
Rare in immunosuppressed but COMMON in AIDS! (AIDS-defining illness) Invariably fatal |
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How does JCV cause CNS disease?
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Altered JCV sequences found in CNS
HIV makes Tat protein that helps get JCV into brain |
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BK virus
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Like JCV, exists in bladder and kidneys at low levels
Major cause of kidney transplant rejection (immunosuppression --> reactivation) |
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Do polyomaviruses cause cancer?
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Merkel cell polyomavirus is most strongly linked (Merkel cell carcinoma)
BKV = risk factor in urothelial tumors Even if polyomaviruses do not cause cancer, the presence of large T-antigen could contribute (b/c k.o. p53 + Rb) |
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Parvovirus replication
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1. Hairpin loops used by cellular enzymes to convert ssDNA --> dsDNA
2. Conversion to dsDNA requires cell to undergo S phase, uses cellular DNA pol with hairpin 3' as primer 3. Cellular RNA polymerase II for transcription 4. Viral and host proteins both required for genome replication 5. Release by cell lysis |
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Members of parvovirus family
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Parvovirus B19
Adeno-associated virus (AAV): causes no disease but important as gene therapy vector because can integrate into chromosome |
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Clinical manifestation of parvovirus B19
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Erythema infectiosum/Fifth disease (especially in kids 4-15 y.o.)
1. prodromal period with mild, flu-like illness 2. in 1-2 weeks, facial rash with "slapped cheek" appearance 3. Infect erythroid precursors -- if sickle cell disease or hemolytic anemia --> aplastic crisis If pregnant women --> fetal anemia + death or hydrops fetalis (fetal anemia + CHF) Especially bad in seronegative mom --> increased risk of fetal death |
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Parvovirus transmission
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Respiratory droplets, transplacental
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Diagnosis of parvovirus infection
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B19-specific IgM antibody
PCR |
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Pathogenesis of parvovirus B19
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Initiates infection in respiratory tract followed by viremia
Infects erythroid precursors in BM, replicates preferentially in proliferating hematopoietic cells Cytolytic to immature erythroid cells --> erythropoiesis suppression + anemia If immunocompetent, recovery associated with antibody response that clears virus and confers long-term protection |
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"Slapped cheek appeareance"
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Erythema infectiosum/Fifth disease due to parvovirus B19
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Hydrops fetalis
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Parvovirus B19
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Major cause of kidney transplant rejection
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BK virus
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Vesicular rash in mouth and vesiculopustular rash on body with vomiting, diarrhea, bleeding
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Smallpox (variola virus)
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Nodular/wart-like lesion with central plug that is readily expressed on trunk, genitalia, and proximal extremities
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Molluscum contagiosum virus
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Conjunctivitis
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Adenovirus
Acute febrile pharyngitis Pharyngoconjunctival fever |
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Demyelinating disease in AIDS patient
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Progressive multifocal leukoencephalopathy due to JC virus in brain
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Highly aggressive skin cancer associated with UV exposure
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Merkel cell carcinoma due to Merkel cell polyomavirus
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Medically important herpesviruses
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HSV-1
HSV-2 VZV EBV CMV HHV-6 HHV-7 KSHV (HHV-8) Get herpes in a CHEVrolet |
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Common features of infection with herpesviruses
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Primary, acute infections are most often asymptomatic
All infected persons become latently infected Most infected with herpesviruses 1-7 |
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Transmission of herpesviruses
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1. HSV-1/-2, CMV, EBV, HHV-6/-7 (possibly KSHV/HHV-8) transmitted by direct contact with contaminated secretions/body fluid
HSV-1/-2: vesicular fluid from lesions, saliva, vaginal secretions CMV: saliva, urine, semen, vaginal/cervical secretions, blood, breast milk EBV and HHV-6/-7: saliva 2. VZV: transmitted by respiratory droplets All can be transmitted sporadically by these body fluids in the absence of clinical symptoms during acute infection or reactivation from latency |
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Primary infection with HSV-1/-2, CMV, EBV, HHV-6/-7/-8
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1. Initial replication in oral or genital epithelial cells
2. Local spread (HSV only) Systemic spread via viremia to multiple organs 3. Cells infected harbor latent virus: HSV -- neurons (trigeminal or sacral) CMV, EBV, HHV-6/-7/-8 -- blood mononuclear cells |
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Primary infection with VZV
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1. Initial replication in epithelial cells of upper respiratory tract
2. Systemic spread via viremia to spleen, liver, skin, oral mucosa 3. Cells infected harbor latent virus: innervating sensory neurons |
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Only herpesvirus that has only local spread during primary infection
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HSV-1/-2
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Which herpesvirus set up latent infection in trigeminal or sacral ganglia
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HSV-1/-2
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Which herpesvirus set up latent infection in neurons and which neurons?
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HSV-1/-2 in trigeminal or sacral ganglion
VZV in dorsal root ganglion |
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Which herpesvirus set up latent infection in blood mononuclear cells and which cells?
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CMV - mononuclear cells
EBV - B cells HHV-6/-7 - T cells KSHV (HHV-8) - B cells |
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Pathogenesis of VZV
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Infect respiratory epithelial cells and lymph nodes
Primary viremia Replication in spleen, liver 10-21 days Secondary viremia Disseminated to epithelial cells of skin, mucous membranes, mononuclear cells. Immune clearance of virus but VZV genome remains latent in sensory neuron (DRG) |
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Clinical manifestations of HSV-1/-2
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herpetic gingivostomatitis (HSV-1): painful vesicular and ulcerative lesions in facial areal and oral mucosa with fever, sore throat
herpes labialis: reactivation of oral herpes (cold sores) herpetic keratoconjunctivitis (HSV-1): 2nd leading cause of corneal blindness in U.S. herpetic whitlow: HSV-1/-2 infection of fingers eczema herpeticum herpes genitalis (HSV-1/-2): vesicular and ulcerative lesions of penis, cervix, vulva, vagina, perineum; dysuria herpes proctitis herpes meningitis: complication of HSV-2 herpes genitalia herpes encephalitis: most common fatal sporadic viral encephalitis. Occur after primary or recurrent infection. HSV-1 in adults, HSV-2 in neonate. |
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Which reactivates more frequently, HSV-1 or HSV-2
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HSV-2
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Transmission of HSV-1/-2
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Direct contact with virus-containing secretions and body fluids, e.g. saliva and genital secretions during sexual contact
Neonatal infection transmitted from infected maternal secretion to newborn during delivery Infected individuals can shed infectious virus in absence of clinical symptoms |
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Pathogenesis of HSV-1/-2
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Localized, lytic infection of mucosal epithelial cells (no systemic spread)
Latent infection follows of trigeminal ganglia with herpetic gingivostomatitis and sacral/lumbar ganglia with herpes genitalis Reactivation of latentcy triggered by external factors that induce virus to travel down axon and infect epithelial cells innervated by the sensory nerve --> recurrent vesicular lesions |
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Clinical manifestation of VZV
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Primary infection = varicella: generalized vesicular rash --> pustule --> crust (5-7 days)
Reactivation characterized by unilateral, localized, painful, vesicular lesions with dermatomal distribution. |
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Most common fatal sporadic viral encephalitis
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HSV-2 in infants
HSV-1 in adults |
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Transmission of VZV
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Respiratory droplets
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VZV latent state location
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Dorsal root ganglion
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Clinical manifestation of CMV
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Mononucleosislike syndrome in older children and adults (fever, sore throat, fatigue, malaise, lympadenopathy like EBV mono)
Congenital infection: 1% of all infants infected by asymptomatic. If primary infection of pregnant mom --> cytomegalic inclusion disease (hepatomegaly, splenomegaly, petechiae, jaundice, microencephally, deafness, mental retardation) Reactivates intermittently and shed from asymptomatic pts in body fluids Severe disease in immunocompromised. 1. HIV: retinitis, colitis, encephalitis 2. transplant recipient: pneumonia, myelosuppression, hepatitis, encephalitis, GI disease, allograft rejection, allograft dysfunction, death |
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Pathogenesis of CMV
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Initiates infection in oropharynx and usually causes subclinical, asymptomatic infection.
Virus spreads to lymphoid tissue -- replicates in monocytes, macrophages, endothelial cells and --> viremia Dissemination to multiple organs Remains latent in mononuclear cells and reactivated in immunosuppressed |
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Transmission of CMV
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Direct contact with bodily fluids (saliva, urine, semen, cervical secretions, breast milk, blood)
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Treatment of CMV
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Ganciclovir and valganciclovir (antivirals): guanosine analogs phosphorylated by viral phosphotransferase
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Clinical manifestation of HHV-6/-7
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Primary infection: exanthem subitum (roseola) = high fever followed by generalized, erythmatous and macular rash
In children |
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Transmission of HHV-6/-7
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Saliva
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HHV-6/-7 set up latency where
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T-lymphocytes
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Clinical manifestation of KSHV/HHV-8
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1. Kaposi's sarcoma: infected endothelial cells --> transformation of spindle cells --> vascular neoplasia
Virus expresses oncogenes, regulators of cell cycle (cyclin D, B cell growth factors IL-6, 8, 17) 2. Primary effusion B cell lymphoma 3. Multicentric Castleman disease: B-cell lymphoproliferative disorder |
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Transmission of KSHV/HHV-8
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Saliva and semen
Almost exclusively in MSM |
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KSHV/HHV-8 sets up latency where
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B cells
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Clinical manifestation of EBV
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Infectious mononucleosis in young adults: fever, sore throat, fatigue, malaise, lymphadenopathy, splenomegaly, elevated liver enzymes
Associated with lymphoproliferative disorders Closely linked to Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin disease |
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Transmission of EBV
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Saliva
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Pathogenesis of EBV
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Initiates infection of oropharyngeal epithelial cells --> spread to infiltrating B cells via binding to receptor C3d --> latent infection
Subsequent phase of permanent proliferation due to expression of EBV regulatory genes whose products control B cell cycle (immortalization) Resting B cells differentiate into plasma cells - secretion of IgM antibodies = Monospot test CTL prevent uncontrolled growht of EBV-infected B cells Hyperproliferative B cells and activated CTLs --> splenomegaly and lymphadenopathy |
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Burkitt's lymphoma results from
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Result of EBV + c-myc/Ig variable region translocation
Possible scenarios 1. EBV immortalized and dividing B cells have increased chance of translocation 2. EBV immortalizes the rare B cells that have the transolcation 3. EBV is passenger virus and has no role |
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Monospot test result for EBV vs. CMV
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EBV = Monospot positive
CMV = Monospot negative |
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Treatment of HSV-1/-2
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Acyclovir, valacyclovir (antivirals) - guanosine analog phosphorylated by viral thymidine kinase
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Treatment of VZV
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Acyclovir, valacyclovir (antivirals) - guanosine analog phosphorylated by viral thymidine kinase
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Prevention of VZV
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Varivax = live, attenuated virus
Zostavax = same as Varivax but 10x the amount of infectious virus |
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Unique characteristics of Hepatitis B virus
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Partially dsDNA, brings own RT
large quantities of noinfectious viral protein secreted from infected hepatocytes (Dane particles) high incidence of chronic infection etiologic agent of hepatocellular carcinoma |
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Transmission of hepatitis B virus
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IVDA, sexual intercourse
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Clinically important member of hepadnavirus
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Hepatitis B virus
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Clinical manifestation of hepatitis B virus
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Acute hepatitis: hepatomegaly, elevated liver enzymes, tea-colored urine, pale stool, jaundice. Sx are result of cell-mediated immune response.
Chronic hepatitis: limited cell-mediated response so mild sx; can lead to liver cirrhosis, liver failure, hepatocellular carcinoma |
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Markers of acute HBV infection vs chronic HBV infection
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acute: HBsAg, HBeAg 1st detected then disappear with anti-HBs and anti-HBe antibodies
chronic: HBsAg, HBeAg for 6 months or more (never detect anti-HBs antibody) |
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Hepatocyte injury in HBV is probably due to?
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CTL-specific for HBcAg or HBeAg
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Risk factors for hepatocellular carcinoma?
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age, HBV, liver cirrhosis
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Viral bugs causing gastroenteritis
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Caliciviruses
Astroviruses Reoviruses (rotavirus) Enteric adenovirus |
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Medically relevant Caliciviruses
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Norovirus
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Clinical manifestations of Norovirus
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Acute gastroenteritis: older children and adults. Acute onset of vomiting, diarrhea, nausea, abdominal cramps, and fever.
Short incubation (24 hrs) and short duration of illness (1-2 days) Diarrhea is generally watery w/o blood or mucus. |
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Transmission of Norovirus
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Fecal-oral
Cruise ships -- but 60-80% of outbreaks occur on land Ingestion contaminated food/water, direct person-to-person contact, fomites Low infectious dose Excrete virus in stool for several weeks after recovery Resistant to chlorine and drying |
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Most common cause of acute gastroenteritis outbreaks among adults in U.S.
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Norovirus
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Most common cause of acute gastroenteritis outbreaks in children in U.S.
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Astrovirus and Rotavirus
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Pathogenesis of norovirus
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Directly damages enterocytes
Binds A, B, or O blood group antigen on surface Microvilli broadened and blunted Transient malabsorption and reduced gastric motility Norovirus antibody detected after infection and confers short-term protection but role of immunity is incomplete |
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Diagnosis of Norovirus
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RT-PCR assay of stool samples
EIA for norovirus-specific IgM in serum |
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Norovirus as a "hit-and-run" virus concept
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Efficient strategy for infection
1. acid stable 2. reproduce quickly 3. exit host before immune system can become fully activated |
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Prototypical member of Astrovirus family
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Astrovirus serotype 1
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Clinical manifestations of Astrovirus type 1
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Acute gastroenteritis in infants and young kids.
Vomiting, abdominal pain, fever, watery diarrhea that is self-limiting |
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Transmission of astrovirus type 1
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Fecal-oral route, usually person-to-person contact or contaminated food/water
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Peak season for astrovirus type 1
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Winter months
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#1 cause of viral diarrhea in what population?
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Infants
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Pathogenesis of astrovirus type 1
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Infects and damages enterocytes but there is *distinct lack of inflammation or cell death*
Serum IgG antibody correlated with viral clearance and protective immunity |
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Virulence factors of astrovirus type 1
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Capsid increases epithelial barrier permeability ("enterotoxin" activity)
Capsid protein suppresses complement activation by binding and inhibiting C1 activation |
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Diagnosis of astrovirus type 1
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EIA for viral antigen
RT-PCR for genomic RNA |
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Clinical manifestations of hepatitis E virus
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Water-borne epidemics of hepatitis
Most infections subclinical Abrupt onset if symptomatic and generally self-limiting Fulminant hepatitis is major complication of HEV infection in pregnant women, especially 3rd trimester |
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Transmission of HEV
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Fecal-oral route usually by contaminated water
Most common cause of acute hepatitis in developing countires w/poor sanitation. |
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Pathogenesis of HEV
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Similar to HAV. No chronic infection or carrier state.
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Diagnosis of HEV
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HEV-specific IgM or IgG antibody by EIA
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Medically important members of Reovirus family
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Colorado Tick Fever virus (CTFV)
Rotavirus |
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Unique aspects of Reoviruses
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Segmented dsDNA ("repeato"-virus)
Contains RdRp as part of virion Genetic reassortment and antigenic variation |
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Clinical manifestations of CTFV
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Acute febrile illness (fever, myalgia, chills, headache, malaise, abdominal pain, vomiting)
Saddle-back fever pattern: 2-3 day febrile period then afebrile period and then fever returns (50% patients) Complication: encephalitis or hemorrhagic fever, especially in kids Generally mild/subclinical infection |
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Transmission of CTFV
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Arbovirus -- infected wood tick
Western U.S. Natural reservoir = small animals Viral zoonosis |
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Pathogenesis of CTFV
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Enters skin via tick bite
Replicates in hematopoietic cells, including erythrocyte precursors --> leukopenia and thrombocytopenia due to direct cytopathic effects Virus persists in RBCs, masked from immune clearance Recovery associated with elevated neutralizing antibody levels |
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Diagnosis of CTFV
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Direct immunofluorescent staining of blood smears for CTFV antigens on RBC surface
EIA for IgM or IgG |
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Clinical manifestations of rotavirus
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acute viral gastroenteritis in infants and young children
sudden onset of nausea, low-grade fever, vomiting, and non-bloody, watery diarrhea lasting 4-5 days Dehydration + electrolyte loss = major complications Pts w/malnutrition and immunodeficiencies are at increased risk of developing severe rotavirus infections. |
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Transmission of rotavirus
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Fecal-oral route
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Peak incidence of rotavirus in what population?
Peak season? Which group is most common cause of diarrheal disease? |
Infants 6-24 months old (but can occur in all age groups)
Lasts 1-4 months each winter Group A most common |
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Pathogenesis of rotavirus
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After ingestion, rotavirus infect and lyse enterocytes --> slough --> stunted villi.
Malabsorption --> hyperosmotic effect --> diarrhea Intestinal secretory IgA correlated with immunity to reinfection. |
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Virulence factors of rotavirus
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NSP4 = enterotoxin capable of inducing diarrhea.
Segment genome -- genetic reassortment and antigenic shift |
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Diagnosis of rotavirus
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EIA for antigen in stool
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Prevention of rotavirus
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RotaTeq and Rotarix = vaccines
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