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.
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
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.
Date: Mar. 11, 2005
PubMed ID: 15611076
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