Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus.

Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus.
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DOI:
10.1126/science.1185350
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发表时间:
2010-04-02
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Früh K
Früh K
中科院分区:
其他
文献类型:
--
作者:
Hansen SG;Powers CJ;Richards R;Ventura AB;Ford JC;Siess D;Axthelm MK;Nelson JA;Jarvis MA;Picker LJ;Früh K

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尽管CMV特异性的体液和细胞免疫,但巨细胞病毒(CMV)仍可以持续感染的宿主持续感染。但是,这样做仍然不确定。在这里,我们证明了恒河神CMV感染的恒河猴的超级感染(RM)需要通过病毒编码的MHC-I抗原呈递的抑制剂来逃避CD8+ T细胞免疫,尤其是人类CMV US的同源物。相比之下,MHC-1的干扰对于初次感染了RM,或在CMV感染的RM中持续的二次感染暂时消耗了CD8+淋巴细胞。这些发现表明,US2-11糖蛋白在体内促进逃避CD8+ T细胞的逃避,因此在超级感染过程中支持病毒复制和传播,这一过程使预防性CMV疫苗的发展变得复杂,但可以利用基于CMV的基于CMV的载体开发。
Cytomegalovirus (CMV) can super-infect persistently infected hosts despite CMV-specific humoral and cellular immunity; however, how it does so remains undefined. Here, we demonstrate that super-infection of rhesus CMV-infected rhesus macaques (RM) requires evasion of CD8+ T cell immunity by virally-encoded inhibitors of MHC-I antigen presentation, particularly the homologues of human CMV US2, 3, 6 and 11. In contrast, MHC-I interference was dispensable for primary infection of RM, or for the establishment of a persistent secondary infection in CMV-infected RM transiently depleted of CD8+ lymphocytes. These findings demonstrate that US2-11 glycoproteins promote evasion of CD8+ T cells in vivo thus supporting viral replication and dissemination during super-infection, a process that complicates the development of preventative CMV vaccines, but that can be exploited for CMV-based vector development.
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