A child with encephalitis has CSF showing lymphocytic pleocytosis and hemorrhagic necrosis of temporal lobes on MRI. HSV-1 encephalitis is suspected. The molecular mechanism of HSV-1 latency reactivation involves:
- A Insertion of HSV-1 genome into host chromosome leading to constitutive transcription
- B Production of alpha (immediate-early) proteins ICP4/ICP22 during latency maintaining episomal state
- C Reactivation of viral lytic gene expression when LAT-derived miRNAs fail to suppress ICP0 ✓
- D VZV-mediated superinfection activating HSV-1 from the trigeminal ganglion
Explanation
During latency in neurons, HSV-1 expresses only LAT (latency-associated transcripts); LAT-derived microRNAs (miR-H2, miR-H6) suppress ICP0 and ICP4 (immediate-early transcription activators) maintaining latency. Reactivation occurs when stress/immunosuppression reduces this suppression, allowing ICP0 expression which derepresses the entire lytic program. HSV-1 exists as circular episomes in neurons, NOT integrated into host chromosomes (unlike retroviruses). Alpha proteins ICP4 and ICP22 are expressed during lytic infection, not during latency. VZV causes separate varicella/zoster; coinfection does not reactivate HSV.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.