The poxviral scrapin MV-LAP requires a myxoma viral infection context to efficiently downregulate MHC-I molecules

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• 作者：Nicolas Collin ; Jean-Luc Gué ; rin ; Ingo Drexler ; Sophie Blanié ; Jacqueline Gelfi ; Sé ; verine Boullier ; Gilles Foucras ; Gerd Sutter and Fré ; dé ; rique Messud-Petit
• 关键词：Poxviruses ; Myxomatosis ; Myxoma virus ; MHC-I ; Regulation ; Cell surface receptors ; Virulence ; Viral proteins ; Ubiquitin
• 刊名：Virology
• 出版年：2005
• 出版时间：20 December 2005
• 年：2005
• 卷：343
• 期：2
• 页码：171-178
• 全文大小：414 K

文摘

Downregulation of MHC class I molecules is a strategy developed by some viruses to escape cellular immune responses. Myxoma virus (MV), a poxvirus causing rabbit myxomatosis, encodes MV-LAP that is known to increase MHC-I endocytosis and degradation through a C₄HC₃ motif critical for an E3 ubiquitin ligase activity. Here, we performed a functional mapping of MV-LAP and showed that not only the C₄HC₃ motif is necessary for a marked downregulation of MHC-I but also a conserved region in the C-terminal part of the protein. We also showed that the putative transmembrane domains are responsible for a specific subcellular localization of the protein: they retain MV-LAP in the ER in transfected cells and in the endolysosomal compartments in infected cells. We observed that a specific MV infection context is necessary for a fully efficient downregulation of MHC-I. Our data suggest that the functionality of viral LAP factors, inherited by herpes- and poxviruses from mammalian cells, is more complex than anticipated.