Journal article
Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation
Proceedings of the National Academy of Sciences - PNAS, Vol.108(38), pp.15834-15839
09/20/2011
DOI: 10.1073/pnas.1101676108
PMCID: PMC3179061
PMID: 21876179
Abstract
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′ 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′ 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′ and 3′ mRNA degradation machinery to specifically promote the degradation of multiply spliced HIV-1 mRNAs.
Details
- Title: Subtitle
- Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation
- Creators
- Yiping Zhu - Graduate School of the Chinese Academy of SciencesGuifang Chen - Chinese Academy of SciencesFengxiang Lv - Chinese Academy of SciencesXinlu Wang - Chinese Academy of SciencesXin Ji - Chinese Academy of SciencesYihui Xu - Chinese Academy of SciencesJing Sun - Chinese Academy of SciencesLi Wu - Ohio State UniversityYong-Tang Zheng - Chinese Academy of SciencesGuangxia Gao - Chinese Academy of Sciences
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.108(38), pp.15834-15839
- DOI
- 10.1073/pnas.1101676108
- PMID
- 21876179
- PMCID
- PMC3179061
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 09/20/2011
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984002389802771
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