Knickelbein Jared E, Khanna Kamal M, Yee Michael B, Baty Catherine J, Kinchington Paul R, Hendricks Robert L
Graduate Program in Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Science. 2008 Oct 10;322(5899):268-71. doi: 10.1126/science.1164164.
Reactivation of herpes simplex virus type 1 (HSV-1) from neuronal latency is a common and potentially devastating cause of disease worldwide. CD8+ T cells can completely inhibit HSV reactivation in mice, with interferon-gamma affording a portion of this protection. We found that CD8+ T cell lytic granules are also required for the maintenance of neuronal latency both in vivo and in ex vivo ganglia cultures and that their directed release to the junction with neurons in latently infected ganglia did not induce neuronal apoptosis. Here, we describe a nonlethal mechanism of viral inactivation in which the lytic granule component, granzyme B, degrades the HSV-1 immediate early protein, ICP4, which is essential for further viral gene expression.
1型单纯疱疹病毒（HSV-1）从神经元潜伏状态重新激活是全球常见且可能具有毁灭性的疾病病因。CD8 + T细胞可完全抑制小鼠体内的HSV重新激活，其中γ干扰素提供了部分这种保护作用。我们发现，CD8 + T细胞的溶细胞颗粒对于体内和体外神经节培养中神经元潜伏状态的维持也是必需的，并且它们向潜伏感染神经节中与神经元的连接处的定向释放不会诱导神经元凋亡。在这里，我们描述了一种病毒失活的非致死机制，其中溶细胞颗粒成分颗粒酶B降解了HSV-1立即早期蛋白ICP4，而ICP4对于进一步的病毒基因表达至关重要。
