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Journal of Virology, September 2009, p. 8674-8682, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00653-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Patch of Positively Charged Amino Acids Surrounding the Human Immunodeficiency Virus Type 1 Vif SLVx4Yx9Y Motif Influences Its Interaction with APOBEC3G {triangledown}

Gongying Chen,1,2 Zhiwen He,1,3 Tao Wang,1 Rongzhen Xu,3 and Xiao-Fang Yu1,3*

Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205,1 Sixth Hospital of Hangzhou, Zhejiang,2 Second Affiliated Hospital, Cancer Institute, School of Medicine, Zhejiang University, Zhejiang, China3

Received 30 March 2009/ Accepted 1 June 2009

The amino-terminal region of the Vif molecule in human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIV) contains a conserved SLV/Ix4Yx9Y motif that was first described in 1992, but the importance of this motif for Vif function has not yet been examined. Our characterization of the amino acids surrounding this motif in HIV-1 Vif indicated that the region is critical for APOBEC3 suppression. In particular, amino acids K22, K26, Y30, and Y40 were found to be important for the Vif-induced degradation and suppression of cellular APOBEC3G (A3G). However, mutation of these residues had little effect on the Vif-mediated suppression of A3F, A3C, or A3DE, suggesting that these four residues are not important for Vif assembly with the Cul5 E3 ubiquitin ligase or protein folding in general. The LV portion of the Vif SLV/Ix4Yx9Y motif was found to be required for optimal suppression of A3F, A3C, or A3DE. Thus, the SLV/Ix4Yx9Y motif and surrounding amino acids represent an important functional domain in the Vif-mediated defense against APOBEC3. In particular, the positively charged K26 of HIV-1 Vif is invariably conserved within the SLV/Ix4Yx9Y motif of HIV/SIV Vif molecules and was the most critical residue for A3G inactivation. A patch of positively charged and hydrophilic residues (K22x3K26x3Y30x9YRHHY44) and a cluster of hydrophobic residues (V55xIPLx4-5Lx{Phi}x2YWxL72) were both involved in A3G binding and inactivation. These structural motifs in HIV-1 Vif represent attractive targets for the development of lead inhibitors to combat HIV infection.

* Corresponding author. Mailing address: Department of Molecular 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 17 June 2009.

Journal of Virology, September 2009, p. 8674-8682, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00653-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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