Latent Herpes Simplex Virus in Human Trigeminal Ganglia. Detection of an Immediate Early Gene "anti-sense" Transcript by in Situ Hybridization

We used in situ hybridization to study the expression of herpes simplex virus type 1 genes during latent infections of human sensory ganglia. Trigeminal ganglia were recovered at autopsy from 24 subjects with no evidence of an active herpetic infection. These ganglia were hybridized to 35S-labeled single-stranded RNA probes spanning 72 percent of the herpes simplex genome. In the ganglia of 16 subjects, 0.2 to 4.3 percent of the neuronal cells contained abundant nuclear signals for viral RNA. Ganglia from three patients with low or undetectable levels of antibodies to herpes simplex type 1 lacked viral RNA signals, whereas the ganglia from all of six patients with elevated antibody titers showed viral RNA signals. Transcription was detected only from the region of the viral genome containing a gene that encodes an immediate early protein known as the infected-cell protein number zero (ICP0). However, normal ("sense") transcripts of this gene, which are prominent in an acute infection, were not detected. In contrast, a novel transcript was found overlapping with, but opposite in direction to, the ICP0 transcript (and was therefore "anti-sense"). Although this transcript has been only partially characterized, we believe that it may have a role in maintaining the latency of herpes simplex virus.