Herpes Simplex Virus: Lifelong Infection, Reactivation, and Management

HSV establishes lifelong latency in sensory ganglia (trigeminal for HSV-1, sacral for HSV-2). No current therapy eradicates latent virus.

Lifecycle

1. Primary infection: Mucosal entry → replication → sensory neuron retrograde transport → latency establishment.
2. Latency: Viral genome episomal; only latency-associated transcripts (LATs) expressed. No viral proteins → immune evasion.
3. Reactivation: Stressors (UV, fever, stress, immunosuppression, hormonal) → viral gene expression → anterograde transport → mucosal shedding ± lesions.

Clinical Patterns

• Symptomatic recurrences: prodrome → vesicles → ulcers (2–10 days).
• Asymptomatic shedding: 10–20% of days (HSV-2 genital); major transmission source.

Management

• Episodic therapy: Valacyclovir 1g BID × 1 day or 500mg BID × 3 days at prodrome.
• Suppressive therapy: Valacyclovir 500mg–1g daily → ↓ outbreaks 70–80%, ↓ shedding, ↓ transmission to partners by ~50%.
• Topical: Limited efficacy.
• Counseling: Disclosure, condoms, avoidance during outbreaks, suppressive therapy for serodiscordant couples.

Research Directions

Therapeutic vaccines, gene editing (CRISPR), helicase-primase inhibitors, latency-targeting agents. No cure yet.