Cantin E M, Hinton D R, Chen J, Openshaw H
Department of Neurology, City of Hope National Medical Center, Duarte, California 91010, USA.
J Virol. 1995 Aug;69(8):4898-905. doi: 10.1128/JVI.69.8.4898-4905.1995.
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.
本研究旨在评估γ干扰素（IFN-γ）在单纯疱疹病毒1型（HSV-1）感染中的作用。在小鼠感染的急性期，通过单克隆抗体处理去除IFN-γ的小鼠以及基因敲除IFN-γ受体的小鼠（Rgko小鼠），其三叉神经节和脑干组织中的HSV-1复制虽有适度但持续的增强。通过逆转录酶PCR测定，在HSV-1急性感染和潜伏感染期间，三叉神经节中均存在IFN-γ和肿瘤坏死因子α转录本。在HSV-1接种后第5天，最初在三叉神经节中检测到CD4 +和CD8 + T细胞，这些细胞在潜伏状态下持续存在6个月。T细胞集中在形态正常的神经元周围，这些神经元没有活跃感染的迹象，但其中许多表达HSV-1潜伏相关转录本。在T细胞浸润区域，潜伏长达6个月时仍存在分泌的IFN-γ。到潜伏9个月时，T细胞浸润和IFN-γ表达均已清除，尽管三叉神经节中的巨噬细胞水平仍略有增加。在HSV-1感染的脑干组织中，感染后1个月存在T细胞和IFN-γ表达，但在6个月后消失。我们的假设是，T细胞的持续存在和IFN-γ的持续表达是对神经系统中HSV-1抗原的反应。这一假设与HSV-1潜伏的新模型一致，该模型表明在潜伏期间发生有限的HSV-1抗原表达（M. Kosz-Vnenchak、J. Jacobson、D.M. Coen和D.M. Knipe，《病毒学杂志》67:5383 - 5393，1993年）。我们推测潜伏期间IFN-γ的长期分泌可能调节HSV-1的再激活感染。
