文章基本信息

标题：Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5α
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作者：Theodora Hatziioannou ; David Perez-Caballero ; Annie Yang 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：29
页码：10774-10779
DOI：10.1073/pnas.0402361101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mammalian cells express several factors that act in a cell-autonomous manner to inhibit retrovirus replication. Among these are the Friend virus susceptibility factor 1/lentivirus susceptibility factor 1/restriction factor 1 (Ref1) class of restriction factors, which block infection by targeting the capsids of diverse retroviruses. Here we show that lentivirus susceptibility factor 1 and Ref1 are species-specific variants of tripartite interaction motif 5{alpha} (TRIM5{alpha}), a cytoplasmic body component recently shown to block HIV-1 infection in rhesus macaque cells, and can indeed block infection by widely divergent retroviruses. Depletion of TRIM5{alpha} from human cells relieved restriction of N-tropic murine leukemia virus (N-MLV), and expression of human TRIM5{alpha} in otherwise nonrestricting cells conferred specific resistance to N-MLV infection, indicating that TRIM5{alpha} is Ref1 or an essential component of Ref1. TRIM5{alpha} variants from humans, rhesus monkeys, and African green monkeys displayed different but overlapping restriction specificities that were quite accurately predicted by the restriction properties of the cells from which they were derived. All TRIM5{alpha} variants could inhibit infection by at least two different retroviruses, and African green monkey TRIM5{alpha} was able to inhibit infection by no less than four divergent retroviruses of human, non-human primate, equine, and murine origin. However, each TRIM5{alpha} variant was unable to restrict retroviruses isolated from the same species. These data indicate that TRIM5{alpha} can confer broad innate immunity to retrovirus infection in primate cells and is likely to be an important natural barrier to cross-species retrovirus transmission.