ID 6.1516
Terms
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Human Herpes Viruses
(general) -
Large
Enveloped
dsDNA (makes sense b/c latency!) -
Human Herpes Viruses
(Classification Scheme) - Alpha, Beta and Gamma Subfamilies
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Human Herpes Viruses
(Alpha Subfamily) -
Include HHV 1/2/3 and Herpes simiae (Herpes B)
Characterized by rapid cell growth, variable host range and latency in sensory ganglio -
Human Herpes Viruses
(Beta Subfamily) -
CMV (5) and HHV6
SLOW GROWTH (culture)
Latency in CD4/Monocytes/Macs/Mesenchymal cells -
Human Herpes Viruses
(Gamma Subfamily) -
4 (EBV) and 8 (Kaposi's Sarcoma HIV)
POOR GROWTH -
Herpes
(Virus-Host Interactions) -
All encode enzymes involved in NA metabolism (important in antiviral therapy!)
Lysis/latency
Reactivation of latent phase may be symptomatic or asymptomatic - Herpes Simplex Viruses
- HHV 1 & 2
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HSV
(Structure) -
As HHVs, they're enveloped w/dsDNA
They're envelope is coated with glycoproteins that facilitate their attachment to cells but also enable serotyping - How do you serologically distinguish HSV1 and HSV2?
- Serology is based on antibodies to gG (envelope glycoprotein)
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HSV1 vs. HSV2
(Seroepidemiology) -
HSV1: indidence begins at childhood (most adults seropositive)
HSV2: incidence at puberty & less than 1/2 adults seropositive -
HSV Infections
(Pathogenesis) -
Inoculate skin/mucous membranes
Productive infection of surrounding area and sensory neurons
LATENCY (in sensory ganglia)
External/internal stressors result in reactivation of infection (majority are subclinical) - HSV Primary Infection
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Generally subclinical
Most common manifestation = PAINFUL vesicular rash - HSV Rash Evolution
- Erythema, Papule, Vesicle, Pustule, Ulcer, Scab
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HSV 1
(Typical Primary Infections) -
Gingivostomatitis
Keratoconjunctivitis -
HSV 1
(Typical Recurrent Disease) - Herpes labialis
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HSV 2
(Typical Primary Infection) - Genital/neonatal herpes
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HSV 2
(Recurrent disease) - Genital Herpes
- HSV and the Immunocompromized Host
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MORE FREQUENT
DISSEMINATED INFECTIONS are cause of significant mortality - Shared Clinical Syndrome of HSV 1 and 2
- ENCEPHALITIS
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HSV
(Diagnosis) -
Tzank Smear (multinucleated giant cells w/inclusions)
Culture
or serology - Tzank Smear
- Multinucleated Giant cells w/inclusions (seen in HSV lesions)
- HHV 3
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Varicella-Zoster Virus
Chickenpox and Shingles -
VZV
(Epidemiology) -
Majority of US adults are seropositive
Primary infections at childhood
Incidence of recurrent infection increase with age -
VSV
(Pathogenesis) -
Aerosol or direct contact
Latency established in sensory ganglia (note: you have this interstitial viremia which causes virus to set up shop in multiple dermatomes) -
VSV
(Primary Infection) -
Symptomatic
"Chickenpox"
Morbidity greater in adults vs. children
Serious complications if immunocompromized
Primary infection during pregnancy may give rise to birth defects - Reye Syndrome and VSV
- Associated w/aspirin treatment
- Reye Syndrome
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Unexplained GI problems (vomiting/diarrhea)
Generally afebrile
"Brain Fevor" symptoms . . . lethary . . . delerium later, etc - Herpes Zoster
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Reactivated latent VSV infection
Dermatomal banding pattern
More severe in immunecompromized host -
VSV
(Prevention and Control) -
Live vaccine recommended for 1 yr olds
Must isolate VSV infection in hospital
Immune globulin possible for those at risk for severe infecotion - Cytomegalovirus
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CMV (HHV 5)
As HHV, tells you its dsDNA and enveloped -
CMV
(Risk Factors) -
Day Care
Promiscuity (Homosexuality)
Blood/transplant recipients -
CMV
(Routes of Transmission) -
Perinatal
Intimate contact
Blood transfusion/transplants -
CMV
(Clinical Presentation) - Majority of infecotions are ASYMPTOMATIC but 3 groups of symptomatic infections exist (depends on host state)
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CMV
(Symptomatic Infections) -
(1) Fetus/Neonate
(2) Older children/adults
(3) Immunocompromized -
CMV
(Fetal/Neonatal Infection) -
Severe, disseminated disease
Fever, jaundice, hepatospenlomegaly, anemia/thrombocytopenia, lymphocytosis - What is the most common congenital infection?
- CMV
- What is the most common cause of viral-induced deafness/MR?
- CMV
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CMV
(Older Children/Adults) - Systemic infection mimics Infectious Mononucleosis (due to EBV)
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CMV
(Immunocompromized Host) -
Hepatitis
Retinitis
Encephalitis
Colitis -
CMV
(Diagnosis) - Detect viral antigen/DNA (via PCR), IgM or histopathology (see cytoplasmic/nuclear inclusions)
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EBV
(general) -
Epstein-Barr Virus
HHV4 (tells you enveloped, as dsDNA) -
EBV
(Seroepidemiology) -
Vast majority seropositive
In children, infections are generally subclinical
Most common presentation in young adults -
EBV
(Pathogenesis) -
Replication in oropharynx and B cell infection
EBV stimulates proliferation of B cells and CMI/humoral response - What causes symptoms of EBV infection (mono)?
- The immune response to B cell proliferation
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EBV
(Clinical Manifestations) -
(1) Infectious Mononucleosis (fever, sore throat and lymphadenopathy)
(2) OHL
(3) Cancer - OHL
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Oral Hairy Leukoplakia
Seen in HIV patients
Lytic EBV replication on tongue epithelium
NOTE: EBV is required but not sufficient for OHL - EBV and Cancer
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Nasopharyngeal carcinom
African-type Burkitt's Lymphoma
Non-Hodkin's Lymphoma
Hodkin's Disease
NOTE: these cancers arise in *10%* of transplant patients (b/c their immune system is so shoddy - if you cut back on immunosuppressive drugs, these cancers may regress) -
EBV
(Diagnosis) -
1) CBC w/diff: Lymphocytosis w/atypical lymphocytes
2) Heterophile antibodies (during acute infection)
3) anti-VCA (viral capside antigen) IgM antibodies (for specific diagnosis) - What should you look for to specifically diagnose acute EBV infection?
- IgM antibodies to VCA (viral capsid antigen)
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EBV
(Managment of Symptoms) -
Steroids (if airway obstruction, thromobocytopenia/anemia, etc)
Avoid contact sports (splenic rupture) -
HHV 6
(general) -
Beta HHV Subfamily (?)
Tells you it's enveloped, dsDNA -
HHV 6
(Clinical Manifestations) -
MAJORITY of cases are SYMPTOMATIC
Causes Roseola (a.k.a. SIXTH disease) - high fever and following rash -
HHV 8
(general) -
Gamma HHV virus (enveloped, dsDNA)
a.k.a. Kaposi's Sarcoma-Associated Herpesvirus (KSHV) -
HHV 8
(Epidemoiology) -
Low seroprevalence in US
Higher seroprevalence in Mediterranean/East African Population
HIGH seroprevalence (75%) in HIV patients -
HHV 8
(Transmission - Endemic Areas) - Oral and suggested mother-child
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HHV 8
(Transmission) -
Patterns of sexual transmission (virus predominates in saliva and other secretions)
NOTE: different route of infection in endemic countries (likely oral) b/c acquired during childhood -
HHV 8
(Diseases) - Tumors (Kaposi's Sarcoma), primary effusion/body cavity lymphomas, AIDS-related multicentric Castleman's Disease
- Herpes Simiae
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Herpes B
Primate herpes that is highly infectious among humans, with severe CNS complications
Generally follows animal bites
NOTE: antiviral therapy EXISTS. Therefore, need to catch and treat early!