Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency.

Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency.
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DOI:
10.1126/science.1164164
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发表时间:
2008-10-10
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Hendricks RL
Hendricks RL
中科院分区:
其他
文献类型:
--
作者:
Knickelbein JE;Khanna KM;Yee MB;Baty CJ;Kinchington PR;Hendricks RL

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单纯疱疹病毒1型从神经元潜伏期的再激活是世界范围内常见的和潜在的破坏性疾病原因。CD 8 + T细胞可以完全抑制小鼠中的HSV再活化,IFN-γ提供了部分保护作用。在这里,我们发现,CD 8 + T细胞裂解颗粒也需要在体内和离体神经节培养的神经元潜伏期的维持,并在潜伏感染的神经节中,它们的定向释放到与神经元的交界处不诱导神经元凋亡。我们描述了一种非致死性的病毒灭活机制,其中裂解颗粒组分,颗粒酶B,降解单纯疱疹病毒1型立即早期蛋白,ICP 4,这是必要的进一步的病毒基因表达。
Reactivation of herpes simplex virus type 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 IFN-γ affording a portion of this protection. Here, 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. We describe a non-lethal mechanism of viral inactivation in which the lytic granule component, granzyme B, degrades the herpes simplex virus type 1 immediate early protein, ICP4, which is essential for further viral gene expression.
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