Vaccinia virus entry, exit and evasion

目前由流感病毒和人类免疫缺陷病毒引起的流行病表明，病毒仍然是对人类健康的有力威胁。对病毒如何复制、传播和逃避我们的免疫防御的基础研究对于增进我们对病毒如何致病的理解非常重要，并将为新疫苗和抗病毒药物的开发奠定基础。这项提案涉及牛痘病毒(VACV)、一种天花病毒和用于根除天花的活疫苗。虽然天花已被根除，但VACV仍在继续研究，因为：i)VACV有可能被改造成预防其他传染病的疫苗，以及ii)VACV与宿主细胞和免疫系统之间的相互作用正在提供关于病毒如何致病的新的基本信息。这项应用将重点研究VACV如何进入细胞，新的病毒颗粒如何运输出细胞，这些病毒颗粒如何快速传播到其他细胞，以及VACV如何逃避感染的免疫反应。所获得的信息将有助于将VACV设计为一种更安全、更具免疫原性的传染病和癌症疫苗。

Viruses remain a potent threat to human health as illustrated by the current epidemics caused by influenza virus and human immunodeficiency virus. Basic research on how viruses replicate, spread and evade our immunological defences is important in advancing our understanding of how viruses cause disease and will underpin the development of new vaccines and anti-viral drugs. This proposal concerns vaccinia virus (VACV), a poxvirus and the live vaccine that was used to eradicate smallpox. Although smallpox has been eradicated, VACV continues to be studied because i) it is possible to engineer VACV as a vaccine against other infectious diseases, and ii) the interaction between VACV and the host cell and immune system is providing novel, fundamental information about how viruses cause disease. This application will focus on how VACV enters cells, how new virus particles are transported out of the cell, how these virus particles spread rapidly to other cells, and how VACV evades the immune response to infection. The information obtained will facilitate the engineering of VACV as a safer and more immunogenic vaccine for infectious diseases and cancer.