HSV

One-Sentence Definition

Herpes simplex viruses (HSV-1 and HSV-2) are enveloped double-stranded DNA herpesviruses that cause oral/genital lesions and severe disease (encephalitis, neonatal herpes), establishing lifelong latency in sensory ganglia with periodic reactivation.

Taxonomy & Structure

  • Family Herpesviridae, subfamily Alphaherpesvirinae
  • Linear dsDNA; icosahedral capsid; tegument; lipid envelope with glycoproteins (gB, gD…)
  • HSV-1 traditionally oral/encephalitis; HSV-2 traditionally genital — substantial overlap epidemiologically

Replication & Pathogenesis Highlights

  • Lytic replication in epithelium → retrograde transport to ganglia → latency (episomal DNA, latency-associated transcripts)
  • Reactivation → anterograde return to mucosa/skin (triggers: stress, UV, immunosuppression)
  • Immune evasion and neuronal sanctuary sites prevent sterilizing clearance
  • Contrast with VZV/CMV/EBV — same family, different niches (expand later)

Clinical Syndromes

  • Orolabial herpes; genital herpes; herpetic whitlow; eczema herpeticum
  • HSV encephalitis (often temporal lobe; HSV-1) — neurologic emergency
  • Keratitis → vision threat
  • Neonatal herpes (SEM, CNS, disseminated) — perinatal transmission
  • Severe disease in immunocompromised hosts

Diagnosis

  • PCR / qPCR of lesion swab, CSF (encephalitis), blood (neonatal/disseminated) — method of choice
  • Tzanck smear / culture historically; serology for past exposure (type-specific IgG) not for acute CNS decisions
  • DNA Extraction from CSF/swabs; multiplex meningitis/encephalitis panels (Syndromic Molecular Panels)

Treatment Notes (conceptual)

  • Acyclovir / valacyclovir / famciclovir — thymidine kinase–dependent activation
  • IV acyclovir for encephalitis and neonatal disease
  • Resistance (TK or polymerase mutations) in immunocompromised — foscarnet/cidofovir territory
  • Suppression therapy for frequent genital recurrences; no cure for latency

Genomics & Computational Notes

  • Resistance genotyping of UL23 (TK) / UL30 (pol)
  • CSF PCR quantification sometimes used; presence matters more than titer for encephalitis diagnosis
  • Not typically WGS’d for routine care; outbreak typing rare vs respiratory viruses

Active Recall

  1. Where does HSV establish latency?
  2. First-line drug class and activation requirement?
  3. Preferred test for suspected HSV encephalitis?