MECHANISMS OF T CELL ESCAPE BY ORTHOPOXVIRUSES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本研究的长期目标是了解猴痘病毒（MPV）和牛痘病毒（CPV）毒力的病毒免疫调节剂的作用。在2003年爆发期间感染MPV的个体产生了强烈的MPV特异性T细胞应答，但MPV特异性T细胞在体外不被MPV感染的抗原呈递细胞（APC）刺激。相比之下，由疫苗株痘苗病毒（VV）WR感染APC激活来自MPV感染个体的交叉反应性CD 8+和CD 4 + T细胞。这些数据强烈表明，MPV通过表达VV中不存在的免疫调节剂来防止T细胞刺激。同样，我们观察到CPV感染的细胞不刺激T细胞。 我们成功地鉴定了负责T细胞逃避的CPV基因产物。我们目前正在评估MPV基因组中的同源基因抑制T细胞刺激的能力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long-term goal of this study is to understand the role of viral immune modulators for monkeypox virus (MPV) and cowpox virus (CPV) virulence. Individuals infected with MPV during the 2003 outbreak developed a strong MPV-specific T cell response, but the MPV-specific T cells were not stimulated by MPV-infected antigen presenting cells (APC) in vitro . In contrast, infection of APC by the vaccine strain Vaccinia-virus (VV) WR activated cross-reactive CD8+ and CD4+ T cells from MPV-infected individuals. These data strongly suggest that MPV prevents T cell stimulation by expressing immunomodulators that are absent in VV. Similarly, we observed that CPV-infected cells did not stimulate T cells. We succeeded in identifying the gene products of CPV that are responsible for T cell evasion. We are currently evaluating homologous genes in the MPV-genome for their ability to inhibit T cell stimulation.