Herpes simplex virus type 1 (HSV-1) establishes latency in sensory neurons, a state in which the viral lytic genes are silenced and only the latency locus is transcriptionally active, producing the 2.0- and 1.5-kb latency-associated transcripts (LATs). The acidic carboxy terminus of Vmw65 is not involved in assembly of the complex but is absolutely required for subsequent transcriptional activation. At 0, 15 and 60 min after exposure the virus was assayed for infectivity using HEp-2 cells as the host. We rationally designed mutations in gD to displace the C terminus and observe if fusion could be activated without receptor binding. We mapped these sites to within a few amino acids at positions 365-370 408/409. Furthermore, a proof-of-concept double-blind placebo-controlled trial indicated improvement in cognitive performance following supplemental anti-herpes–specific medication among HSV1 seropositive schizophrenia patients. Further understanding of these viral immune evasion mechanisms could be exploited for better management of HSV infection.
Eighty-seven of the exposed embryos and 74 control empryos developed normally 2 to 3 d post hatching with no morpnological differences between the two groups. The strongest association between cognitive functioning and serological evidence of HSV-1 infection was with the domain of delayed memory. Protein analyses were done as described in Fig. The Val/Val genotype of the COMT Val158Met polymorphism was also significantly associated with the RBANS total score and with a moderate decrease in the domain of attention. PCR analysis with primers flanking the LAT sequence revealed the expected splice junction for LAT excision in RNA from sensory neurons latently infected with wild-type but not mutant virus.