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 and brain stem tissue was modestly but consistently enhanced in mice from which IFN-gamma was by ablated monoclonal antibody treatment and in mice genetically lacking the IFN-gamma receptor (Rgko mice). As determined by reverse transcriptase PCR, IFN-gamma and tumor necrosis factor alpha transcripts were present in trigeminal ganglia during both acute 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 focused around morphologically normal neurons that showed no signs of active infection, but many of which expressed HSV-1 latency-associated transcripts. Secreted IFN-gamma was present up to 6 months into latency in areas of the T-cell infiltration. By 9 months into latency, both the T-cell infiltrate and IFN-gamma expression had cleared, although there remained a slight increase in macrophage levels in trigeminal ganglia. In HSV-1-infected brain stem tissue, T cells and IFN-gamma expression 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 IFN-gamma expression occur in response to an HSV-1 antigen(s) in the nervous system. This hypothesis is consistent with a new model of HSV-1 latency which suggests that limited HSV-1 antigen expression occurs during latency (M. Kosz-Vnenchak, J. Jacobson, D.M. Coen, and D.M. Knipe, J. Virol. 67:5383-5393, 1993). We speculate that prolonged secretion of IFN-gamma during latency may modulate a reactivated HSV-1 infection.
Cantin
E M
EM
Department of Neurology, City of Hope National Medical Center, Duarte, California 91010, USA.
Hinton
D R
DR
Chen
J
J
Openshaw
H
H
D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D017931:DNA Primers; D005260:Female; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000276:immunology* / Q000821:virology; D017471:Receptors, Interferon / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014709:Vero Cells; D017735:Virus Latency; D014779:Virus Replication; D000096743:Interferon gamma Receptor
D017931:DNA Primers; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor