👄 HSV-1 Latency Reactivation Simulator

Primary Infection and Ganglion Establishment

HSV-1 enters epithelial cells then climbs sensory nerves to the ganglion.

• Mucosa/skin: Entry route (oral epithelium contact)
• ~400 mm/day: Retrograde speed (dynein-driven transport)
• Trigeminal: Target ganglion (cranial nerve V)
• ~67%: Global seroprevalence (adults under 50)

Initial mucosal infection

Placeholder: virus replicates briefly at the entry site.

Retrograde axonal travel

Placeholder: capsids move along microtubules toward the cell body.

Arrival at the ganglion

Placeholder: genome reaches the neuronal nucleus.

Latent Viral Genome Persistence

The viral genome persists as a quiet episome without producing virus.

• Episomal: Genome form (circular, non-integrated)
• LAT only: Gene expressed (latency-associated transcript)
• Lifelong: Latency duration (in most hosts)
• ~1 in 10³: Neurons harboring virus (ganglion estimate)

Episomal chromatinization

Placeholder: host histones silence lytic gene promoters.

LAT transcript role

Placeholder: LAT RNA helps maintain the dormant state.

Immune surveillance

Placeholder: CD8+ T cells patrol without clearing the genome.

Trigger-Induced Reactivation Signal

Stress, UV light, or fever can flip the latency switch back on.

• UV, stress: Common triggers (fever, immunosuppression)
• JNK pathway: Key signal (stress kinase activation)
• Hours–days: Onset window (after trigger exposure)
• Variable: Reactivation rate (depends on host immunity)

Stress kinase signaling

Placeholder: cellular stress pathways derepress viral genes.

Immediate-early gene burst

Placeholder: ICP0 and friends restart the lytic program.

Escape from immune control

Placeholder: local immune surveillance is briefly overwhelmed.

Anterograde Axonal Transport

Newly made virions travel outward along the axon toward the skin.

• Anterograde: Transport direction (kinesin motors)
• ~2–8 mm/hr: Typical speed (fast axonal transport)
• Enveloped virion: Cargo form (or transport vesicle)
• Several cm: Axon length (ganglion to lip)

Kinesin motor cargo

Placeholder: virions hitch rides on microtubule motor proteins.

Sorting at the terminal

Placeholder: cargo is released near nerve endings in skin.

Timing to symptom onset

Placeholder: transport precedes visible lesion formation.

Viral Shedding at Lip Epithelium

Virions infect epithelial cells at the lip, producing a visible cold sore.

• Vesicular: Lesion type (herpes labialis)
• ~7–10 days: Shedding duration (typical episode)
• Common: Asymptomatic shedding (even without lesion)
• Frequent: Recurrence (variable per individual)

Epithelial re-infection

Placeholder: virions enter keratinocytes at the nerve terminal.

Lesion formation

Placeholder: local replication produces the classic cold sore.

Return to latency

Placeholder: the ganglion resumes dormancy after the episode.