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Journal of Virology, September 2009, p. 8544-8552, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00651-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Identification of a Novel WxSLVK Motif in the N Terminus of Human Immunodeficiency Virus and Simian Immunodeficiency Virus Vif That Is Critical for APOBEC3G and APOBEC3F Neutralization{triangledown}

Ying Dang, Xiaojun Wang, Tao Zhou, Ian A. York, and Yong-Hui Zheng*

Departments of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824-4320

Received 30 March 2009/ Accepted 4 June 2009

The function of lentiviral Vif proteins is to neutralize the host antiviral cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F). Vif bridges a cullin 5-based E3 ubiquitin ligase with A3G and A3F and mediates their degradation by proteasomes. Recent studies have found that Vif uses different domains to bind to A3G and A3F. A 14DRMR17 domain binds to A3F, 40YRHHY44 binds to A3G, and 69YxxL72 binds to both A3G and A3F. Here, we report another functional domain of Vif. Previously, we demonstrated that human immunodeficiency virus type 1 (HIV-1) Vif failed to mediate A3G proteasomal degradation when all 16 lysines were mutated to arginines. Here, we show that K26, and to a lesser extent K22, is critical for A3G neutralization. K22 and K26 are part of a conserved 21WxSLVK26 (x represents N, K, or H) motif that is found in most primate lentiviruses and that shows species-specific variation. Both K22 and K26 in this motif regulated Vif specificity only for A3G, whereas the SLV residues regulated Vif specificity for both A3F and A3G. Interestingly, SLV and K26 in HIV-1 Vif did not directly mediate Vif interaction with either A3G or A3F. Previously, other groups have reported an important role for W21 in A3F and A3G neutralization. Thus, 21WxSLVK26 is a novel functional domain that regulates Vif activity toward both A3F and A3G and is a potential drug target to inhibit Vif activity and block HIV-1 replication.

* Corresponding author. Mailing address: 2215 Biomedical and Physical Sciences, Michigan State University, East Lansing, MI 48824-4320. Phone: (517) 884-5314. Fax: (517) 353-8957. E-mail: zhengyo{at}msu.edu

{triangledown} Published ahead of print on 17 June 2009.

Journal of Virology, September 2009, p. 8544-8552, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00651-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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