HIV-1 Vif can directly inhibit apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G-mediated cytidine deamination by using a single amino acid interaction and without protein degradation.

Unidade de Retrovirus e Infeccoes Associadas, Centro de Patogenese Molecular, Faculdade de Farmacia, Universidade de Lisboa, Av. das Forcas Armadas, 1649-019 Lisboa, Portugal.
The human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G), also known as CEM-15, is a host-cell factor involved in innate resistance to retroviral infection. HIV-1 viral infectivity factor (Vif) protein was shown to protect the virus from APOBEC3G-mediated viral cDNA hypermutation. The mechanism proposed for protection of the virus by HIV-1 Vif is mediated by APOBEC3G degradation through ubiquitination and the proteasomal pathway. Here we show that in Escherichia coli the APOBEC3G-induced cytidine deamination is inhibited by expression of Vif without depletion of deaminase. Moreover, inhibition of deaminase-mediated bacterial hypermutation is dependent on a single amino acid substitution D128K that renders APOBEC3G resistant to Vif inhibition. This single amino acid was elegantly proven by other authors to determine species-specific sensitivity. Our results show that in bacteria this single amino acid substitution controls Vif-dependent blocking of APOBEC3G that is dependent on a strong protein interaction. The C-terminal region of Vif is responsible for this strong protein-protein interaction. In conclusion, our experiments suggest a complement to the model of Vif-induced degradation of APOBEC3G by bringing to relevance that deaminase inhibition can also result from a direct interaction with Vif protein.
Mesh Terms:
Amino Acid Sequence, Amino Acid Substitution, Apolipoproteins B, Binding Sites, Cytidine Deaminase, Gene Products, vif, HIV-1, Humans, Molecular Sequence Data, Mutagenesis, Site-Directed, Nucleoside Deaminases, Protein Conformation, Proteins, RNA Editing, RNA, Messenger, Repressor Proteins, vif Gene Products, Human Immunodeficiency Virus
J. Biol. Chem. Mar. 11, 2005; 280(10);8765-75 [PUBMED:15611076]
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