APOBEC3B and APOBEC3C Are Potent Inhibitors of Simian Immunodeficiency Virus Replication

• Published in: The Journal of biological chemistry 2004-12, Vol.279 (51), p.53379-53386
• Main Authors: Yu, Qin, Chen, Darlene, König, Renate, Mariani, Roberto, Unutmaz, Derya, Landau, Nathaniel R.
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - pharmacology; Apolipoproteins B - chemistry; Apolipoproteins B - physiology; Catalysis; CD4-Positive T-Lymphocytes - metabolism; Cell Line; Cell Line, Tumor; Cytidine Deaminase - chemistry; Cytidine Deaminase - metabolism; Cytidine Deaminase - physiology; DNA, Complementary - metabolism; Gene Products, vif - metabolism; Genes, Reporter; Genetic Vectors; Green Fluorescent Proteins - metabolism; HIV-1 - metabolism; Human immunodeficiency virus 1; Humans; Lentivirus - genetics; Lentivirus - metabolism; Luciferases - metabolism; Macrophages - metabolism; Minor Histocompatibility Antigens; Mutation; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; Simian immunodeficiency virus; Simian Immunodeficiency Virus - metabolism; Transcription, Genetic; Transfection; vif Gene Products, Human Immunodeficiency Virus; Virus Replication
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M408802200

In the human genome the apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC)3 gene has expanded into a tandem array of genes termed APOBEC3A-G. Two members of this family, APOBEC3G and APOBEC3F, have been found to have potent activity against virion infectivity factor deficient (Δvif) human immunodeficiency virus 1 (HIV-1). These enzymes become encapsidated in Δvif HIV-1 virions and in the next round of infection deaminate the newly synthesized reverse transcripts. The lentiviral Vif protein prevents the deamination by inducing the degradation of APOBEC3G and APOBEC3F. We report here that two additional APOBEC3 family members, APOBEC3B and APOBEC3C, have potent antiviral activity against simian immuno-deficiency virus (SIV), but not HIV-1. Both enzymes were encapsidated in HIV-1 and SIV virions and were active against Δvif SIVmac and SIVagm. SIV Vif neutralized the antiviral activity of APOBEC3C, but not that of APOBEC3B. APOBEC3B induced abundant G → A mutations in both wild-type and Δvif SIV reverse transcripts. APOBEC3C induced substantially fewer mutations. APOBEC3F was found to be active against SIV and sensitive to SIVmac Vif. These findings raise the possibility that the different APOBEC3 family members function to neutralize specific lentiviruses.