HSV 1&2 Flashcards
What is going on with the HSV when is it latent?
Its genome, but not progeny, exist in trigeminal and/or sacral ganglia; only gene expressed is LAT
What is going on with the HSV when is it reactivated?
It produces progeny that infect epithelial cells innervated by the latently-infected neurons
4 herpesviruses that are sexually transmitted
HSV 1, HSV 2, CMV, KSHV
(T/F): Acyclovir is the curative treatment of choice for HSV-1 and HSV-2 that works by terminating chain elongation.
False - No herpes treatments are curative! The rest of the statement is true.
How does HSV get into cells?
Direct fusion with the plasma membrane in a pH-INDEPENDENT manner
Immediate early genes
Transcription factors that switch host RNA polymerase to preferential viral gene transcription
Early genes
Proteins needed for replications
Late genes
Structural proteins
Two important HSV early genes
Thymidine kinase, DNA polymerase
Where does HSV replicate?
Nucleus of epithelial cells
Thymidine kinase mutants are particularly prevalent in what population?
AIDS patients with concurrent HSV infx
causes ACV resistance
Where does HSV assembly occur? Why do we care?
Nucleus; forms nuclear inclusion bodies (vacuoles with bugs in them) that are diagnostic
Describe the pathogenesis of the multinucleated giant cells seen in Tzanck smears
Same viral glycoproteins that allow HSV to fuse with plasma membranes are expressed on the membrane late in infection, allowing the infected cell to fuse with neighboring cells
What type of cells are visualized with Tzanck smears?
Epithelial cells; virus only produces glycoproteins when it’s replicating, and it only replicates in epithelial cells
Function of only HSV gene produced during latency?
LAT = produces RNA that silences some cellular genes to prevent apoptosis of the infected cell
Is HSV enveloped?
YES! (think: it has to fuse with plasma membrane)
If the HSV genome is observed to be extrachromosomal, what is happening?
Latency
HSV 1 or 2: cervicitis
2
HSV 1 or 2: encephalitis
1
HSV 1 or 2: meningitis
2
HSV 1 or 2: herpetic whitlow
1
HSV 1 or 2: keratitis
2
HSV 1 or 2: penile/vulvar vesicles
2
HSV 1 or 2: gingivostomatitis
1
HSV 1 or 2: herpes labialis
1
Who gets disseminated herpes upon reinfection?
Immunocompromised patients
Who gets disseminated herpes upon primary infection?
Neonates (think eczema herpeticum)
A patients present with small penile vesicles that he has never had before. If this is a primary HSV 2 infection, when did he most likely contract the virus?
2 weeks ago
Why are recurrent HSV infections shorter than primary infections?
Neutralizing antibodies developed after the primary infection will be present
Primary oral HSV 1 or 2
Gingivostomatitis
Recurrent oral HSV 1 or 2
Herpes labialis
Manifestation of primary HSV 1 or 2 infection in females
Internal or external vesicles, mucopurulent cervicitis, vaginitis, rarely urethritis
Pattern of recurrence in HSV 2 infections
More frequent soon after primary infection then diminish in frequency over time
More frequent recurrence: HSV 1 or HSV 2 genital lesions
HSV 2
Genital HSV prodrome
Flu-like sx, itching/burning in infected areas, leg/buttocks muscle aches
Cause of HSV encephalitis in neonates
Primary HSV 2
Cause of HSV encephalitis in adults
Recurrent HSV 1
Sx of HSV encephalitis
Fever, HA, confusion, seizures
70% mortality if untreated
Herpes encephalitis
Cause of HSV meningitis
Primary HSV 2
Incidence of HSV meningitis
10% of primary HSV 2 infections
Sx of HSV meningitis
HA, stiff neck, fever, vomiting
Mortality of HSV meningitis
Usually resolves in 1 week
You were worried that your OB patient with a primary HSV 2 infection may transmit the virus during delivery despite ACV treatment (C/S was contraindicated). A couple days after delivery the mother states she is relieved that her baby didn’t get the virus as he has not developed any herpetic signs. You inform her that:
Neonatal herpes doesn’t present until 1-2 weeks after delivery and the infant has a 30% chance of being infected so be on the lookout for a rash
75% morbidity/mortality
Severe neonatal herpes
Manifestations of neonatal herpes
Zoster-form rash, encephalitis, disseminated infection leading to organ failure
More common: adult or neonatal HSV encephalitis
Neonatal
You notice your OB patient has a primary HSV infection at the time of labor. What do you do?
C-section!
Rate of transmission of primary HSV infection during delivery
30%
Rate of transmission of secondary HSV infection during delivery
2-3%
Incidence of neonatal HSV transmitted transplacentally
5%
Incidence of neonatal HSV transmitted during vaginal delivery
95%
Dx of oral herpes
Clinical
Dx of genital herpes
- Culture and look for cytopathic effect
- Fluorescent antibody screening of virus culture
- PCR
- Tzank smear
- Serology to detect anti-glycoprotein G Abs
Which diagnostic tests for genital herpes can differentiate between HSV 1 and HSV 2?
PCR and serology
Which diagnostic test for genital herpes only tells you the patient has had a herpes infection at some point and why?
Serology; you’re detecting anti-glycoprotein G Abs, so you know patient was exposed to HSV at one point but not that there is an active infection
Dx keratitis
Slit lamp to look for corneal damage
can you tell apart syphilis from HSV?
Dx HSV meningitis
Culture CSF to look for cytopathic effect
Main point of diagnosing HSV meningitis
Rule out bacterial meningitis, which is more severe than the self-resolving aseptic (viral) meningitis
Dx HSV encephalitis
PCR + Southern blot of CSF
EEG to rule it out if normal
Tests that are no good for dx HSV encephalitis
- Culture of CSF - rarely positive
2. Antibody tests - don’t develop for 1-2 weeks and need to treat ASAP
Dx disseminated HSV in neonate
Liver enzymes + other diagnostic methods mentioned
Rules out HSV encephalitis
Normal EEG
Why does ACV not attack host DNA polymerase?
The first phosphate must be added by viral thymidine kinase
DOC for ACV treatment failure
Foscarnet because it doesn’t have to be phosphorylated