Bit · Micro
Herpesviruses — HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-8
Eight human herpesviruses, all dsDNA, all establish latency, all reactivate under stress. The pivot is the latency site and the syndrome of reactivation.
Mechanism
All herpesviruses share core biology: enveloped, large linear double-stranded DNA, replicate in the nucleus, and establish lifelong latency in a characteristic cell type. The differences are in which cells they infect, where they hide, and what they reactivate as.
- HSV-1 (HHV-1) — orolabial herpes (cold sores). Most common cause of sporadic encephalitis in adults (temporal lobe). Latent in trigeminal ganglion.
- HSV-2 (HHV-2) — genital herpes. Neonatal infection via vaginal delivery → high morbidity/mortality. Latent in sacral ganglia.
- VZV (HHV-3) — primary infection: varicella (chickenpox). Reactivation: zoster (shingles), in a dermatomal distribution. Latent in dorsal root ganglia.
- EBV (HHV-4) — infectious mononucleosis (fever, pharyngitis, lymphadenopathy, atypical lymphocytes). Latent in B cells. Linked to Burkitt lymphoma (t(8;14)), nasopharyngeal carcinoma, Hodgkin, CNS lymphoma in HIV.
- CMV (HHV-5) — mononucleosis-like illness in immunocompetent (heterophile-negative). In neonates: TORCH agent → periventricular calcifications, sensorineural hearing loss. In HIV/transplant: retinitis, esophagitis, colitis, pneumonitis. Latent in monocytes.
- HHV-6 — roseola infantum (high fever followed by truncal rash as fever drops). Latent in T cells.
- HHV-7 — also linked to roseola; clinically minor.
- HHV-8 (KSHV) — Kaposi sarcoma (especially in HIV/AIDS), primary effusion lymphoma, multicentric Castleman disease. Latent in B cells.
Differentiator Table
| Virus | Primary illness | Reactivation / disease association | Latency site |
|---|---|---|---|
| HSV-1 | Gingivostomatitis, cold sores | Cold sores, herpes encephalitis (temporal lobe) | Trigeminal ganglion |
| HSV-2 | Genital herpes, neonatal infection | Recurrent genital lesions, aseptic meningitis | Sacral ganglia |
| VZV | Varicella (chickenpox) | Zoster (dermatomal shingles), post-herpetic neuralgia | Dorsal root ganglia |
| EBV | Mononucleosis (heterophile +, atypical lymphocytes) | Burkitt, nasopharyngeal CA, Hodgkin, CNS lymphoma (HIV), oral hairy leukoplakia | B cells |
| CMV | Mononucleosis (heterophile −); TORCH (periventricular calcifications, SNHL) | Retinitis, esophagitis, colitis, pneumonitis in HIV/transplant | Monocytes |
| HHV-6 | Roseola infantum (sudden fever then rash) | Reactivation in immunocompromised | T cells |
| HHV-8 | Often asymptomatic primary | Kaposi sarcoma, primary effusion lymphoma, Castleman disease | B cells / endothelial cells |
The Pivot
Three questions usually settle which one:
- What was the primary syndrome? Cold sores (HSV-1) vs genital (HSV-2) vs chickenpox (VZV) vs mono (EBV/CMV) vs roseola (HHV-6) vs Kaposi (HHV-8).
- Heterophile antibody positive or negative? Positive → EBV. Negative mono → CMV.
- Where is the lesion or cancer? Dermatomal vesicles → VZV. Temporal-lobe encephalitis → HSV-1. Burkitt jaw mass in African child → EBV. Purple skin lesions in AIDS → HHV-8.
NBME-Style Stem
A 32-year-old man with untreated HIV infection (CD4 count 45/mm³) develops blurred vision in his right eye. Fundoscopy shows perivascular hemorrhages and yellow-white retinal infiltrates with a 'pizza-pie' appearance. Which of the following is the most likely cause?
Concept Anchor
All eight human herpesviruses are envelope-bound dsDNA viruses that hide for life in a signature cell type — and the syndrome of reactivation is determined entirely by which cell they're hiding in.