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PMID: 19939923 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

A single amino acid difference in human APOBEC3H variants determines HIV-1 Vif sensitivity.

Journal of virology ·Vol. 84 ·No. 4 ·2010-02-00 ·Pages 1902-11

Zhen A, Wang T, Zhao K, Xiong Y, Yu XF

Abstract

Several variants of APOBEC3H (A3H) have been identified in different human populations. Certain variants of this protein are particularly potent inhibitors of retrotransposons and retroviruses, including HIV-1. However, it is not clear whether HIV-1 Vif can recognize and suppress the antiviral activity of A3H variants, as it does with other APOBEC3 proteins. We now report that A3H_Haplotype II (HapII), a potent inhibitor of HIV-1 in the absence of Vif, can indeed be degraded by HIV-1 Vif. Vif-induced degradation of A3H_HapII was blocked by the proteasome inhibitor MG132 and a Cullin5 (Cul5) dominant negative mutant. In addition, Vif mutants that were incapable of assembly with the host E3 ligase complex factors Cul5, ElonginB, and ElonginC were also defective for A3H_HapII suppression. Although we found that Vif hijacks the same E3 ligase to degrade A3H_HapII as it does to inactivate APOBEC3G (A3G) and APOBEC3F (A3F), more Vif motifs were involved in A3H_HapII inactivation than in either A3G or A3F suppression. In contrast to A3H_HapII, A3H_Haplotype I (HapI), which differs in only three amino acids from A3H_HapII, was resistant to HIV-1 Vif-mediated degradation. We also found that residue 121 was critical for determining A3H sensitivity and binding to HIV-1 Vif.

MeSH Terms
Amino Acid Sequence Amino Acid Substitution Aminohydrolases Base Sequence Cell Line Cytosine Deaminase/antagonists & inhibitors,chemistry,genetics,physiology Genes, vif Genetic Variation HIV-1/genetics,pathogenicity,physiology Haplotypes Host-Pathogen Interactions/genetics,physiology Humans Models, Molecular Molecular Sequence Data Plasmids/genetics Proteasome Endopeptidase Complex/metabolism Protein Structure, Tertiary Recombinant Proteins/chemistry,genetics,metabolism Sequence Homology, Amino Acid Transfection vif Gene Products, Human Immunodeficiency Virus/chemistry,genetics,physiology
Chemicals
Recombinant Proteins vif Gene Products, Human Immunodeficiency Virus vif protein, Human immunodeficiency virus 1 Proteasome Endopeptidase Complex APOBEC3H protein, human Aminohydrolases Cytosine Deaminase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhen Anjie
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Wang Tao
Zhao Ke
Xiong Yong
Yu Xiao-Fang
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
1098-5514
DOI
10.1128/JVI.01509-09
Published
2010-02-00
Epub
2009-00-25
Pages
1902-11
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2812409
Subset
IM
Grants
NIAID NIH HHS · R33 AI078831 · United States
NIAID NIH HHS · R21 AI071769 · United States
NIAID NIH HHS · AI071769 · United States
NIAID NIH HHS · AI062644 · United States
NIAID NIH HHS · R01 AI062644 · United States
NIAID NIH HHS · R01 AI062644-05 · United States
NIAID NIH HHS · R56 AI062644 · United States
External Links
PubMed source DOI: 10.1128/JVI.01509-09 PMC Full Text View journal details
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