Em. Cantin et al., GAMMA-INTERFERON EXPRESSION DURING ACUTE AND LATENT NERVOUS-SYSTEM INFECTION BY HERPES-SIMPLEX VIRUS TYPE-1, Journal of virology, 69(8), 1995, pp. 4898-4905
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.