Herpesviridae Flashcards
List the 8 known human herpes viruses and their primary disease
HSV-1: keratitis, encephalitis, genital herpes, pharyngitis, skin ulcers
HSV-2: genital herpes, aseptic meningitis, neonatal herpes, pharyngitis
VZV: chicken pox, encephalitis, pneumonia, disseminated VZV
EBV: mono, Burkitt’s, nasopharyngeal carcinoma
HCMV: heterophile negative mono, hepatitis, retinitis, colitis
HHV-6: roseola infantum
HHV-7: roseola infantum
HHV-8: Kaposi’s sarcoma
Herpes viruses have 12 _____ in their envelopes and all have a tegument between the nucleocapsid and envelop
glycoproteins
the tegument plays a role in allowing the viruses to take over host cell machinery and initiate infection
Herpes viruses are divided into two categories based on tropism:
neurotropic (HSV-1, HSV-2, VZV) with tropism for nervous tissue and maintain a latent state in neurons
lymphotropic (HCMV, EBV, HHV-6, HHV-7) with ropism for lymphoid cells
- HCMV in monocytes
EBV in B cells
HHV-6 and HHV-7 in T cells
Herpes virus cause ____ infection of the host, meaning there are periods where no infectious virus can be isolated
latent
How do herpes viruses maintain latent infection?
They maintain their genomes as episomal elements that reside in the nucleus of the infected cell
The viral genome does NOT integrate into the host genome
Differentiate the mechanisms of latent infection in neurotropic viruses as as compared to lymphotropic viruses
Neurotropic: neurons are terminally differentiated and do not divide; virus can shut off expression of viral proteins to evade host immunity- expresses only latency associated transcript (LAT) mRNA which is not translated into protein
Lymphotropic: must express a minimal set of genes in dividing lymphoid cells in order to replicate and segregate appropriately. Avoid immune response by preventing MHC expression on the cell surface, encode mimics of immunosuppressive IL-4 and IL-10, encode decoy receptors, encode sequences that cannot be degraded and presented as antigens
Describe the sequence of herpes virus infection
- initial infection of epithelium at site of contact
- localized viral replication and uptake by sensory nerves
- virus loads onto microtubules for retrograde transport
- virus enters nucleus, circulizes
- if cell is permissive, productive infection begins
- newly assembled virions proceed by anterograde transport to the same site where infection was initiated
List some factors that re-initiate latent herpes infection
fever, stress, trauma, steroid hormone changes, UV light
How are herpes viruses transmitted?
close contact
EXCEPT: VZV can be spread by close contact and respiratory secretions
In general, seropositivity for herpes viruses in the population is (high/ low)
high
- HSV-1 90% by age 40
- HSV-2 is genital, increasing in prevalence
- VZV 90% by age 15, increasing with vaccine
- EBV and HCMV 90% in the population, common in day cares
HHV-6 and HHV-7: 90% positive by age 10. mild infections
How is latency of herpes viruses a problem for vaccine development?
Vaccines are generally designed to prevent symptoms, not infection
With herpes viruses, latency means that once you are infected, it is permanent
What are the most common manifestations of HSV-1 infections?
gingivomastitis in children- vesicles are very infectious
herpetic whitlow- HSV ulcers around the fingers of dentists
herpes gladiatorum- HSV ulcers on the cheeks, seen in wrestlers
Keratitis, leading cause of infectious blindness in the US. viral replication kills cells of cornea, each reactivation increases cloudiness
encephalitis, can be very serious wiht high mortality and serious sequelae. tx with antivirals
What are common manifestations of HSV-2 infection?
ulcers on genitalia, with tingling at the site and erythema
ulcers can be entirely internal in women
aseptic meningitis, usually self limiting
Neonatal herpes- highly lethal, must treat with antivirals
What are common manifestations of VZV?
Chicken pox- enters through respiratory route or direct contact of a mucosal surface, then disseminates and seeds the skin and internal organs
Vaccine has reduced incidence of chicken pox but has increased a new rash (highly attenuated, few lesions)
reactivation= zoster or shingles over one dermatome
–> post-herpetic neuralgia
What are common manifestations of HCMV?
cytomegalic inclusion disease: infants with hemolytic anemia, thrombocytopenia, hepatitis, splenomegaly, rash, mental retardation. highest risk if maternal HCMV infection occurs during pregnancy
heterophile negative mononucleosis- often subclinical
Immunocompromise: serious infection in organ transplant, blinding retinitis in AIDS, interstitial pneumonitis in BMT pts
