HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.06-6773comv1 21/1/217    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xiao, Z. Articles by Yu, X.-F. Search for Related Content PubMed PubMed Citation Articles by Xiao, Z. Articles by Yu, X.-F.

Zinc chelation inhibits HIV Vif activity and liberates antiviral function of the cytidine deaminase APOBEC3G

Zuoxiang Xiao^*,, Elana Ehrlich^*, Kun Luo^*,, Yong Xiong^* and Xiao-Fang Yu^*,,1

^* Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; and

Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China

¹Correspondence: Department of Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, USA. E-mail: xfyu{at}jhsph.edu

APOBEC3 proteins are cellular antiviral proteins that are targeted for proteasomal degradation by primate lentiviral Vif proteins. Vif acts as a substrate receptor for the Cullin5 (Cul5) E3 ubiquitin ligase, specifically interacting with Cul5 through a novel H-_x5-C-_x17–18-C-_x3–5-H zinc binding motif. Using the membrane-permeable zinc chelator, N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), we demonstrated a requirement for zinc for Vif function in vivo. Treatment with TPEN at an IC50 of 1.79 µM inhibits Cul5 recruitment and APOBEC3G (A3G) degradation. Zinc chelation prevented Vif function in infectivity assays, allowing the virus to become sensitive to the antiviral activity of A3G. Zinc chelation had no effect on cellular Cul5-SOCS3 E3 ligase assembly, suggesting that zinc-dependent E3 ligase assembly may be unique to HIV-1 Vif, representing a new target for novel drug design.—Xiao, X., Ehrlich, E., Luo, K., Xiong, Y., Yu, X-F. Zinc chelation inhibits HIV Vif activity and liberates antiviral function of the cytidine deaminase APOBEC3G.

Key Words: HIV-1 virion • lentiviral Vif proteins • TPEN • zinc binding motif

This article has been cited by other articles:

				B. J. Stanley, E. S. Ehrlich, L. Short, Y. Yu, Z. Xiao, X.-F. Yu, and Y. Xiong Structural Insight into the Human Immunodeficiency Virus Vif SOCS Box and Its Role in Human E3 Ubiquitin Ligase Assembly J. Virol., September 1, 2008; 82(17): 8656 - 8663. [Abstract] [Full Text] [PDF]

				S. K. Gandhi, J. D. Siliciano, J. R. Bailey, R. F. Siliciano, and J. N. Blankson Role of APOBEC3G/F-Mediated Hypermutation in the Control of Human Immunodeficiency Virus Type 1 in Elite Suppressors J. Virol., March 15, 2008; 82(6): 3125 - 3130. [Abstract] [Full Text] [PDF]

				T. Wang, C. Tian, W. Zhang, K. Luo, P. T. N. Sarkis, L. Yu, B. Liu, Y. Yu, and X.-F. Yu 7SL RNA Mediates Virion Packaging of the Antiviral Cytidine Deaminase APOBEC3G J. Virol., December 1, 2007; 81(23): 13112 - 13124. [Abstract] [Full Text] [PDF]

				R. A. Russell and V. K. Pathak Identification of Two Distinct Human Immunodeficiency Virus Type 1 Vif Determinants Critical for Interactions with Human APOBEC3G and APOBEC3F J. Virol., August 1, 2007; 81(15): 8201 - 8210. [Abstract] [Full Text] [PDF]