APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication.
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 (Deltavif) human immunodeficiency virus 1 (HIV-1). These enzymes become encapsidated in Deltavif 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 Deltavif SIV(mac) and SIV(agm). SIV Vif neutralized the antiviral activity of APOBEC3C, but not that of APOBEC3B. APOBEC3B induced abundant G --> A mutations in both wild-type and Deltavif SIV reverse transcripts. APOBEC3C induced substantially fewer mutations. APOBEC3F was found to be active against SIV and sensitive to SIV(mac) Vif. These findings raise the possibility that the different APOBEC3 family members function to neutralize specific lentiviruses.
Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Qin
Q
Yu
Darlene
D
Chen
Renate
R
König
Roberto
R
Mariani
Derya
D
Unutmaz
Nathaniel R
NR
Landau
D019380:Anti-HIV Agents / Q000494:pharmacology; D001055:Apolipoproteins B / Q000737:chemistry* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002384:Catalysis; D002460:Cell Line; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D018076:DNA, Complementary / Q000378:metabolism; D016346:Gene Products, vif / Q000378:metabolism; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009154:Mutation; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D001055:Apolipoproteins B; D018076:DNA, Complementary; D016346:Gene Products, vif; D015778:Minor Histocompatibility Antigens; D054320:vif Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; D008156:Luciferases; C495794:APOBEC3B protein, human; C495795:APOBEC3C protein, human; D003564:Cytidine Deaminase