{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:57:17Z","timestamp":1791320237646,"version":"4.3.1"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"38","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,9,20]]},"abstract":"<jats:p>The zinc-finger antiviral protein (ZAP) was originally identified as a host factor that inhibits the replication of Moloney murine leukemia virus. Here we report that ZAP inhibits HIV-1 infection by promoting the degradation of specific viral mRNAs. Overexpression of ZAP rendered cells resistant to HIV-1 infection in a ZAP expression level-dependent manner, whereas depletion of endogenous ZAP enhanced HIV-1 infection. Both human and rat ZAP inhibited the propagation of replication-competent HIV-1. ZAP specifically targeted the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. We provide evidence indicating that ZAP selectively recruits cellular poly(A)-specific ribonuclease (PARN) to shorten the poly(A) tail of target viral mRNA and recruits the RNA exosome to degrade the RNA body from the 3\u2032 end. In addition, ZAP recruits cellular decapping complex through its cofactor RNA helicase p72 to initiate degradation of the target viral mRNA from the 5\u2032 end. Depletion of each of these mRNA degradation enzymes reduced ZAP's activity. Our results indicate that ZAP inhibits HIV-1 by recruiting both the 5\u2032 and 3\u2032 mRNA degradation machinery to specifically promote the degradation of multiply spliced HIV-1 mRNAs.<\/jats:p>","DOI":"10.1073\/pnas.1101676108","type":"journal-article","created":{"date-parts":[[2011,8,29]],"date-time":"2011-08-29T22:04:21Z","timestamp":1314655461000},"page":"15834-15839","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":293,"title":["Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation"],"prefix":"10.1073","volume":"108","author":[{"given":"Yiping","family":"Zhu","sequence":"first","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;"},{"name":"Graduate School of the Chinese Academy of Sciences, Beijing 100049, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxiang","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ji","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihui","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research, Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210; 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