人巨细胞病毒通过调控自然杀伤细胞的免疫逃逸机制研究进展

人巨细胞病毒( human cytomegalovirus,HCMV)是疱疹病毒β亚科的DNA病毒,基因组为线状双链DNA,全长约240 kb,编码200种以上基因产物.这些基因产物除参与病毒复制增殖外,还与免疫逃逸有关.HCMV感染后,宿主终身带毒并表现为持续性感染.免疫系统对HCMV有持续的选择压力,HCMV存在于宿主体内的关键是逃逸免疫清除.自然杀伤(NK)细胞是人体的固有免疫淋巴细胞,是抵抗感染和清除病变细胞的第一道防线,在体内阻止感染的发生发展中起到重要作用.NK细胞表面表达多种抑制性和激活性受体,如杀伤细胞凝集素样受体(KLR)中的CD94/NKG2C和免疫球蛋白样转录体受体1( LIR1/ILT2)为抑制性受体；NKG2D、NKp30则为激活性受体.NK细胞清除靶细胞的能力由抑制性和激活性受体所产生的抑制和激活信号的平衡所控制.HCMV感染细胞对NK细胞介导的细胞毒具有明显的抗性作用.迄今为止,已经发现HCMV 7个基因(UL16、UL18、UL40、UL83、UL112、UL141和UL142)可以编码相应产物,通过不同机制调节NK细胞抑制或激活信号,抑制NK细胞激活,从而对抗NK细胞的清除作用.

Research progress of human cytomegalovirus immune evasion mechanism through the regulation of natural killer cells

Human cytomegalovirus (HCMV),the prototype species of the Betaherpesvirinae subfamily,has a linear and double stranded DNA.The length of HCMV DNA is approximately 240 kb.HCMV can encode more than 200 products which are essential forviral replication and immune evasion.HCMV causes lifelong,persistent infections.The survival of HCMV is under continuous selective pressure from the immune system.A key aspect of HCMV's capacity for survival lies in immune avoidance.Natural killer (NK) cells are innate lymphocytes that serve as the first line of defense against infected and transformed cells.NK cells play an important role in limiting infection in vivo and express a wide range of activating and inhibitory receptors on their surface,such as CD94/NKG2C,one of the killer cell lectin-like receptors (KLR),and the leukocyte Ig-like receptor 1 (LIR1 or ILT2 ) are inhibitory receptors； NKG2D and NKp30 are activating receptors.The ability of NK cells to eliminate target cells is controlled by a balance between inhibitory and activating signals generated by inhibitory and activating receptors.HCMV-infected cells are obviously resistant to NK cellmediated cytotoxicity.To date,seven gene (UL16,UL18,UL40,UL83,UL112,UL141 and UL142)-encoding products have been identified to be able to regulate the inhibitory and activating signals and inhibit activation of NK cells via different mechanisms,thus protecting against killing of NK cells.