The intrinsic antiretroviral factor APOBEC3B contains two enzymatically active cytidine deaminase domains.
The mammalian APOBEC3 proteins are cytidine deaminases that function as inhibitors of retrovirus replication and retrotransposon mobility. An issue that has remained controversial is whether the editing of deoxycytidine residues to deoxyuridine is necessary and sufficient for this inhibition or whether APOBEC3 proteins also exert a second, distinct inhibitory mechanism. Here, we present an analysis of the ability of mutants of APOBEC3G and APOBEC3B, both of which contain two consensus cytidine deaminase active sites, to inhibit the replication of human immunodeficiency virus. Our data confirm that APOBEC3G only contains a single, carboxy-terminal active site but, surprisingly, reveal that both cytidine deaminase consensus sequences in APOBEC3B are enzymatically active. Enzymatically inactive mutant forms of APOBEC3G and APOBEC3B were found to retain the ability to inhibit the infectivity of HIV-1 virions produced in their presence by approximately 4-fold and approximately 8-fold, respectively. While this inhibition was significantly less than the level seen with wild-type forms of A3G or A3B, these data, nevertheless argue that the inhibition of HIV-1 by APOBEC3 proteins is at least partly independent of DNA editing.
Bogerd
Hal P
HP
Center for Virology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Wiegand
Heather L
HL
Doehle
Brian P
BP
Cullen
Bryan R
BR
D000071480:APOBEC-3G Deaminase; D019943:Amino Acid Substitution; D044966:Anti-Retroviral Agents / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D003564:Cytidine Deaminase / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015778:Minor Histocompatibility Antigens; D016297:Mutagenesis, Site-Directed; D009700:Nucleoside Deaminases / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary; D017393:RNA Editing; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D044966:Anti-Retroviral Agents; D015778:Minor Histocompatibility Antigens; D012367:RNA, Viral; D012097:Repressor Proteins; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C495794:APOBEC3B protein, human; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase