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Journal of Virology, July 2007, p. 7238-7248, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02584-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cytidine Deaminases APOBEC3G and APOBEC3F Interact with Human Immunodeficiency Virus Type 1 Integrase and Inhibit Proviral DNA Formation{triangledown}

Kun Luo,1,2,{dagger} Tao Wang,1,{dagger} Bindong Liu,1 Chunjuan Tian,1 Zuoxiang Xiao,1,2 John Kappes,3 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 University of Alabama at Birmingham, Birmingham, Alabama 352943

Received 28 November 2006/ Accepted 4 April 2007

APOBEC3G (A3G) is a single-stranded DNA cytidine deaminase that targets retroviral minus-strand DNA and has potent antiviral activity against diverse retroviruses. However, the mechanisms of A3G antiviral functions are incompletely understood. Here we demonstrate that A3G, A3F, and, to a lesser extent, the noncatalytic A3GC291S block human immunodeficiency virus type 1 (HIV-1) replication by interfering with proviral DNA formation. In HIV-1 virions, A3G interacted with HIV-1 integrase and nucleocapsid, key viral factors for reverse transcription and integration. Unlike A3G, the weak antiviral A3C cytidine deaminase did not interact with either of these factors and did not affect viral reverse transcription or proviral DNA formation. Thus, multiple steps of the HIV-1 replication cycle, most noticeably the formation of proviral DNA, are inhibited by both cytidine deamination-dependent and -independent mechanisms.

* 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 11 April 2007.

{dagger} These authors contributed equally to this work.

Journal of Virology, July 2007, p. 7238-7248, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02584-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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