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痘苗病毒通过直接感染对自然杀伤细胞功能的调节

Vaccinia virus modulation of natural killer cell function by direct infection.

作者信息

Kirwan Sheryl, Merriam Deborah, Barsby Nicola, McKinnon Amber, Burshtyn Deborah N

机构信息

Department of Medical Microbiology and Immunology, University of Alberta, 659 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.

出版信息

Virology. 2006 Mar 30;347(1):75-87. doi: 10.1016/j.virol.2005.11.037. Epub 2006 Jan 4.

DOI:10.1016/j.virol.2005.11.037
PMID:16387342
Abstract

Natural Killer (NK) cells have been implicated in the response to poxviruses, but the interaction between NK and infected cells is not well characterized. We show that downregulation of class I major histocompatibility complex (MHC-I) molecules in human cells by vaccinia virus (VV) sensitizes the cells to lysis by NK cells. We provide evidence suggesting that NK cells are infected as a consequence of co-culture with infected target cells. We also show that infection of NK cells leads to a marked depression of cytotoxicity. Moreover, the effect on NK cytotoxicity occurs within hours of infection and is prevented by UV inactivation of the virus but is only partially prevented by blocking late gene expression. VV infection also renders the NK cells more sensitive to inhibitory signals. Together our observations suggest that VV infection of NK cells can modulate their signaling in a manner that prevents them from acting on infected target cells.

摘要

自然杀伤(NK)细胞参与了对痘病毒的反应,但NK细胞与受感染细胞之间的相互作用尚未得到充分表征。我们发现,痘苗病毒(VV)使人类细胞中的I类主要组织相容性复合体(MHC-I)分子下调,从而使这些细胞对NK细胞的裂解敏感。我们提供的证据表明,NK细胞因与受感染的靶细胞共培养而被感染。我们还表明,NK细胞的感染导致细胞毒性显著降低。此外,对NK细胞毒性的影响在感染后数小时内就会出现,并且通过病毒的紫外线灭活可以预防,但通过阻断晚期基因表达只能部分预防。VV感染还使NK细胞对抑制性信号更敏感。我们的观察结果共同表明,NK细胞的VV感染可以以一种阻止它们作用于受感染靶细胞的方式调节其信号传导。

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