HIV-1 Vif protein blocks the cytidine deaminase activity of B-cell specific AID in E. coli by a similar mechanism of action

• DOI: 10.1016/j.molimm.2006.02.005
• Publication Date: 2006-04-01T12:13:31Z
• Authors: Mariana Santa-Marta; Frederico Aires d...; Ana Margarida Fon...; Sylvie Rato; Joao Goncalves
• Keywords: 0301 basic medicine; Biochemistry & Molecular Biology; B-Lymphocytes; Gene Products, vif; Immunology; Molecular Sequence Data; APOBEC-3G Deaminase; Nucleoside Deaminases; 3. Good health; Repressor Proteins; Mice; 03 medical and health sciences; Amino Acid Substitution; Cytidine Deaminase; Mutation; Escherichia coli; HIV-1; vif Gene Products, Human Immunodeficiency Virus; Animals; Humans; Amino Acid Sequence; Gene Rearrangement, B-Lymphocyte

HIV-1 Vif protein protects viral replication in non-permissive cells by inducing degradation of APOBEC3G via ubiquitination and proteasomal pathway, although new studies indicate a putative role in Vif's direct inhibition of APOBEC3G. APOBEC3G is member of a homologous family of proteins with cytidine deaminase activity expressed with characteristic tissue specificity, that in humans consist of APOBEC1, APOBEC2, APOBEC3A-H, APOBEC4 and the activation-induced deaminase (AID), a B lymphoid protein necessary for somatic hypermutation, gene conversion and class switch recombination. In this work we show that Vif can counteract AID's activity in E. coli in absence of specific eukaryotic co-factors necessary for AID induced somatic hypermutation, gene conversion and to stimulate class switch recombination in B-cells. We show that AID inhibition is mediated by a direct protein-protein interaction via unique amino acid D118 an homologous mutant responsible for the species-specific restriction of HIV-1 Vif protein existent for APOBEC3G. These results raise the hypothesis that Vif related proteins can act as a broad inhibitor of deaminase activity. Moreover as AID and Vif evolved in different cellular environments, these results may indicate that Vif related proteins might mimic cellular factors that interact with a structural conserved domain of cytidine deaminases during evolution.