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.