Protein kinase C θ is not essential for T-Cell-Mediated clearance of murine gammaherpesvirus 68
Protein kinase C θ is not essential for T-Cell-Mediated clearance of murine gammaherpesvirus 68
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DOI：
10.1128/jvi.79.11.6808-6813.2005
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发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Sarawar, SR
中科院分区：
文献类型：
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作者：
Giannoni, F;Lyon, AB;Sarawar, SR
小鼠伽马疱疹病毒68(MHV-68)是一种自然产生的啮齿动物病原体，与人类病原体Epstein-Barr病毒和Kaposi肉瘤相关疱疹病毒具有显著的同源性。T细胞对MHV-68的初次清除和小鼠鼻腔感染后的生存至关重要。以往的报道表明，蛋白激酶C theta(PKC Theta)在体外对T细胞的激活和细胞因子的产生是必不可少的。为了确定这种分子在体内对病毒感染的免疫反应中的作用，我们用MHV-68感染了PKCO-/-小鼠。尽管T细胞在病毒清除中起着重要作用，但PKCO-/-小鼠在感染后存活，清除了裂解病毒，并保持了对潜伏期的有效长期控制。在PKC theta(+/+)和PKCO-/-小鼠中，CD8 T细胞的增殖、向肺的转运和细胞毒活性相似，而在PKCO-/-小鼠中，抗病毒抗体和T辅助细胞细胞因子的产生显著低于PKCO+/+小鼠。这些研究表明，在对MHV-68的免疫反应中，对PKC theta的需求是不同的，并表明PKC theta对于导致病毒清除的T细胞激活事件不是必不可少的。
Murine gammaherpesvirus 68 (MHV-68) is a naturally occurring rodent pathogen with significant homology to human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. T cells are essential for primary clearance of MHV-68 and survival of mice following intranasal infection. Previous reports have suggested that protein kinase C theta (PKC theta) is essential for T-cell activation and cytokine production in vitro. To determine the role of this molecule in vivo during the immune response to a viral infection, PKCO-/- mice were infected with MHV-68. Despite the essential role of T cells in viral clearance, PKCO-/- mice survived infection, cleared lytic virus, and maintained effective long-term control of latency. CD8 T-cell expansion, trafficking to the lung, and cytotoxic activity were similar in PKC theta(+/+) and PKCO-/- mice, whereas antiviral antibody and T-helper cell cytokine production were significantly lower in PKCO-/- mice than in PKCO+/+ mice. These studies demonstrate a differential requirement for PKC theta in the immune response to MHV-68 and show that PKC theta is not essential for the T-cell activation events leading to viral clearance.