GAMMA-INTERFERON EXPRESSION DURING ACUTE AND LATENT NERVOUS-SYSTEM INFECTION BY HERPES-SIMPLEX VIRUS TYPE-1

This study was initiated to evaluate a role for gamma interferon (IFN- gamma) in herpes simplex virus type 1 (HSV-1) infection, At the acute stage of infection in mice, HSV-1 replication in trigeminal ganglia an d brain stem tissue was modestly but consistently enhanced in mice fro m which IFN-gamma was by ablated monoclonal antibody treatment and in mice genetically lacking the IFN-gamma receptor (Rgko mice), As determ ined by reverse transcriptase PCR, IFN-gamma and tumor necrosis factor alpha transcripts were present in trigeminal ganglia during both acut e and latent HSV-1 infection. CD4(+) and CD8(+) T cells were detected initially in trigeminal ganglia at day 5 after HSV-1 inoculation, and these cells persisted for 6 months into latency, The T cells were focu sed around morphologically normal neurons that showed no signs of acti ve infection, but many of which expressed HSV-1 latency-associated tra nscripts. Secreted IFN-gamma was present up to 6 months into latency i n areas of the T-cell infiltration. By 9 months into latency, both the T-cell infiltrate and IFN-gamma expression had cleared, although ther e remained a slight increase in macrophage levels in trigeminal gangli a. In HSV-1-infected brain stem tissue, T cells and IFN-gamma expressi on were present at 1 month but were gone by 6 months after infection, Our hypothesis is that the persistence of T cells and the sustained IF N-gamma expression occur in response to an HSV-1 antigen(s) in the ner vous system, This hypothesis is consistent with a new model of HSV-I l atency which suggests that limited HSV-1 antigen expression occurs dur ing latency (M. Kosz-Vnenchak, J. Jacobson, D. M. Coen, and D. M. Knip e, J. Virol. 67:5383-5393, 1993). We speculate that prolonged secretio n of IFN-gamma during latency may modulate a reactivated HSV-1 infecti on.