11 - Neurotropic Viruses: Herpes Simplex and Varicella-Zoster Flashcards
What is the structure of herpesvirus?
Linear DNA genome with icosahedral capsid and envelope. Tegument also surrounds capsid.
180-200 nm; large genome of 100-250 kbp
Labile in the environment: infectious virions survive up to 2 hrs on skin and up to 4 on plastic surfaces.
What subfamily of human herpesviruses are herpes simplex virus and varicella zoster in? What are characteristics of this subfamily?
Alpha.
Short replication cycle, latency primarily in sensory ganglia, and a broader host range.
HHV-1, HHV-2, and HHV-1
What makes a virus a herpesvirus?
Encodes thymidine kinase, an enzyme involved in nucleotide metabolism, DNA polymease, and protein kinase.
Synthesis of viral DNA and capsid assembly occurs in the nucleus, while the rest of the virion is put together in the cytoplasm/golgi.
Tye lifecycles: lytic replication and latency.
Describe a latent infection in terms of the herpesvirus?
- Circular viral DNA is associated with host nucleosomes and is maintained as an episome.
- Very little viral gene expression, most lytic genes are transcriptionally repressed through epigenetic mechanisms.(not well understood what triggers reactivation)
- Reactivated occurs due to alterations in immune system such as damage to neurons or UV irradiation
Herpesviruses are forever, why is this?
While the immune system clears the replicating virus during an acute infection, herpesvirus maintains latency with occasional reactivation for the life of the host.
How are HSV-1 and 2 transmitted? How common are HSV1 and HSV2?
Person-to-person:
- intrauterine (very rare)
- perinatal
- skin-skin
- genital-genital
- oral-genital
- oral-oral
HSV-1: most adults seropositive
HSV2: 17% seropositive (1 in 4 women, 1 in 8 men)
What can cause viral shedding of HSV1 and HSV2?
- Oro-facial lesions
- Genital lesions and secretions
- Saliva
- Tears
- HSV1 more commonly shed from oral cavity, HSV2 more commonly spread from genital tract (above the belt HSV1 usually, below the belt HSV2 usually)
Describe what occurs first in an HSV1 or 2 infection?
- virus transmission to mucosa or abraded epithelium
- Lytic replication in cells at site of innoculation causes primary infection
- Virus infects sensory neurons at site of inoculation and retrograde transport to sensory ganglia occurs, resulting in latency.
What are the sites of latency in HSV1 and HSV2 infections? What is latency characterized by?
HSV1 - trigeminal nerve
HSV2 - sacral ganglia
Expression of group of viral mRNAs called latency-associated transcripts (LATs) that are NEVER translated into protein and function to repress HSV expression.
Where does viral reactivation of HSV1 and 2 occur? What happens next?
In neurons.
New viral capsids are subjected to anterograde transport with mature virions made by the site of inoculation causing reinfection of epithelial cells (recurrent infection).
What is the frequency of reactivation in those with latent HSV2?
High;
In untreated HSV-2+ pts, chance of subclinical reactivation at a genital site is about 25% on a given day.
Reinfection with a different strain is possible but not common (called exogenous infection).
Why do some people can herpes encephalitis?
Because the virus gets confused and goes backwards into the CNS (retrograde) instead of moving anterograde.
This is rare but may occur in elderly pts.
How can you treat herpesvirus?
Target replilcating virus ONLY. No treatments for latent infection.
Nucleoside anologs like acyclovir are treatment of choice - inhibit viral but not cellular DNA synthesis
Rely on immune system to clear cells that lytically replicate herpes.
What resistance occurs to herpesvirus? Are there any vaccines?
Resistance is uncommon but possible, esp in immunocompromised.
No vaccines are currently available.
How does acyclovir (ACV) treat herpesvirus infections?
It’s a suicide inhibitor that competes with dGTP for viral DNA polymerase. (This doesn’t affect cellular DNA pol because the nucleotide is too bulky and doesn’t fit)
The polymerase binds to ACV-PPP irreversibly and ties up the polymerase.
What effect does treatment of genital disease (both HSV1 and HSV2) have on viral shedding?
It reduces shedding by 60-80%
