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Journal of Virology, December 2007, p. 13112-13124, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.00892-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

7SL RNA Mediates Virion Packaging of the Antiviral Cytidine Deaminase APOBEC3G{triangledown}

Tao Wang,1,{dagger} Chunjuan Tian,1,3,{dagger} Wenyan Zhang,1,3,{dagger} Kun Luo,1 Phuong Thi Nguyen Sarkis,1 Lillian Yu,1 Bindong Liu,1 Yunkai Yu,1 and Xiao-Fang Yu1,2*

Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205,1 Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China,2 Jilin University, Changchun, China3

Received 26 April 2007/ Accepted 11 September 2007

Cytidine deaminase APOBEC3G (A3G) has broad antiviral activity against diverse retroviruses and/or retrotransposons, and its antiviral functions are believed to rely on its encapsidation into virions in an RNA-dependent fashion. However, the cofactors of A3G virion packaging have not yet been identified. We demonstrate here that A3G selectively interacts with certain polymerase III (Pol III)-derived RNAs, including Y3 and 7SL RNAs. Among A3G-binding Pol III-derived RNAs, 7SL RNA was preferentially packaged into human immunodeficiency virus type 1 (HIV-1) particles. Efficient packaging of 7SL RNA, as well as A3G, was mediated by the RNA-binding nucleocapsid domain of HIV-1 Gag. A3G mutants that had reduced 7SL RNA binding but maintained wild-type levels of mRNA and tRNA binding were packaged poorly and had impaired antiviral activity. Reducing 7SL RNA packaging by overexpression of SRP19 proteins inhibited 7SL RNA and A3G virion packaging and impaired its antiviral function. Thus, 7SL RNA that is encapsidated into diverse retroviruses is a key cofactor of the antiviral A3G. This selective interaction of A3G with certain Pol III-derived RNAs raises the question of whether A3G and its cofactors may have as-yet-unidentified cellular functions.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205. Phone: (410) 955-3768. Fax: (410) 614-8263. E-mail: xfyu{at}jhsph.edu

{triangledown} Published ahead of print on 19 September 2007.

{dagger} T.W., C.T., and W.Z. contributed equally to this study.


Journal of Virology, December 2007, p. 13112-13124, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.00892-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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