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Multifaceted counter-APOBEC3G mechanisms employed by HIV-1 Vif.
Britan-Rosich, Elena; Nowarski, Roni; Kotler, Moshe.
Afiliação
  • Britan-Rosich E; Department of Pathology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
J Mol Biol ; 410(5): 1065-76, 2011 Jul 29.
Article em En | MEDLINE | ID: mdl-21763507
In the absence of human immunodeficiency virus type 1 (HIV-1) Vif protein, the host antiviral deaminase apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (A3G) restricts the production of infectious HIV-1 by deamination of dC residues in the negative single-stranded DNA produced by reverse transcription. The Vif protein averts the lethal threat of deamination by precluding the packaging of A3G into assembling virions by mediating proteasomal degradation of A3G. In spite of this robust Vif activity, residual A3G molecules that escape degradation and incorporate into newly assembled virions are potentially deleterious to the virus. We hypothesized that virion-associated Vif inhibits A3G enzymatic activity and therefore prevents lethal mutagenesis of the newly synthesized viral DNA. Here, we show that (i) Vif-proficient HIV-1 particles released from H9 cells contain A3G with lower specific activity compared with Δvif-virus-associated A3G, (ii) encapsidated HIV-1 Vif inhibits the deamination activity of recombinant A3G, and (iii) purified HIV-1 Vif protein and the Vif-derived peptide Vif25-39 inhibit A3G activity in vitro at nanomolar concentrations in an uncompetitive manner. Our results manifest the potentiality of Vif to control the deamination threat in virions or in the pre-integration complexes following entry to target cells. Hence, virion-associated Vif could serve as a last line of defense, protecting the virus against A3G antiviral activity.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: HIV-1 / Citidina Desaminase / Produtos do Gene vif do Vírus da Imunodeficiência Humana Limite: Humans Idioma: En Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: HIV-1 / Citidina Desaminase / Produtos do Gene vif do Vírus da Imunodeficiência Humana Limite: Humans Idioma: En Ano de publicação: 2011 Tipo de documento: Article