MicrobiologyTier 2Medical Sciences concept

Herpesvirus latency (EBV in B cells, HSV in neurons, CMV in monocytes)

Core concept

All 8 human herpesviruses establish lifelong latency after primary infection. The site of latency determines the reactivation syndrome.

Virus	Latency site	Reactivation disease
HSV-1/2 (HHV-1/2)	Sensory neurons - trigeminal and sacral dorsal root ganglia	Cold sores, genital herpes, HSV encephalitis (temporal lobe), keratitis
VZV (HHV-3)	Dorsal root and cranial nerve ganglia	Shingles, post-herpetic neuralgia, Ramsay Hunt, zoster ophthalmicus, vasculopathy
EBV (HHV-4)	Memory B lymphocytes (uses CD21/CR2 to enter)	PTLD, Burkitt, nasopharyngeal carcinoma, Hodgkin, oral hairy leukoplakia, CNS lymphoma in HIV
CMV (HHV-5)	Myeloid lineage - monocytes and CD34+ progenitors	Retinitis, colitis, pneumonitis, hepatitis, marrow suppression post-transplant and in HIV
HHV-6/7	Monocytes, lymphocytes, salivary gland	Roseola; post-transplant limbic encephalitis (HHV-6); chromosomally integrated HHV-6 gives a spuriously high PCR
HHV-8 (KSHV)	B lymphocytes, endothelium	Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease

Latency = viral genome retained as an episome, minimal gene expression, no virions -> invisible to CTLs and untouched by antivirals (which target replication)

Reactivation triggers: T-cell immunosuppression (steroids, calcineurin inhibitors, transplant, HIV, chemotherapy, biologics), age (immunosenescence), stress, UV, trauma, fever, malignancy
EBV - primary infection in adolescence = infectious mononucleosis: atypical lymphocytes (activated CD8 cells), heterophile/Monospot antibody, splenomegaly (avoid contact sport 4-6 weeks), maculopapular rash if given amoxicillin
- EBV serology: VCA IgM = acute; VCA IgG + EBNA IgG = past infection; *EBNA takes 6-12 weeks to appear, so VCA IgG positive with EBNA negative means recent infection*
CMV - the commonest congenital infection (sensorineural deafness, periventricular calcification); in transplant the highest-risk pairing is donor-positive / recipient-negative (D+/R-)
Antiviral targets - all act on lytic replication, none clear latency
- Aciclovir/valaciclovir: activated by viral thymidine kinase (HSV, VZV) -> no activity against CMV, which lacks it
- Ganciclovir/valganciclovir: activated by CMV UL97 kinase; myelosuppression is dose-limiting
- Foscarnet (nephrotoxic, electrolyte disturbance) and cidofovir need no viral kinase -> used for UL97-mutant resistant CMV
- Letermovir (terminase inhibitor) - CMV prophylaxis post-HSCT, no marrow toxicity; maribavir for refractory/resistant CMV

Screen serostatus before transplant and before starting significant immunosuppression - CMV, EBV, VZV, HSV, and hepatitis B
Prophylaxis or pre-emptive monitoring: valganciclovir or letermovir for high-risk CMV; aciclovir for HSV/VZV-seropositive patients on intensive immunosuppression
EBV viral load monitoring after transplant -> rising load -> reduce immunosuppression, then rituximab, for PTLD
Shingles prevention: Shingrix (recombinant, adjuvanted) is the correct vaccine in immunocompromised patients - Zostavax is live and contraindicated
- NIP-funded in Australia from age 65, and from 50 for Aboriginal and Torres Strait Islander people and the immunocompromised
HSV encephalitis - start aciclovir IV empirically before the PCR returns; a negative CSF PCR in the first 48 h does not exclude it - repeat
Zoster in a young adult with no obvious cause -> test for HIV

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