The intrinsic antiretroviral factor APOBEC3B contains two enzymatically active cytidine deaminase domains

• Published in: Virology (New York, N.Y.) Vol. 364; no. 2; pp. 486 - 493
• Main Authors: Bogerd, Hal P, Wiegand, Heather L, Doehle, Brian P, Cullen, Bryan R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2007
• Subjects: Amino Acid Substitution; Anti-Retroviral Agents - chemistry; Anti-Retroviral Agents - metabolism; APOBEC-3G Deaminase; APOBEC3G; Cell Line; Cytidine Deaminase - chemistry; Cytidine Deaminase - genetics; Cytidine Deaminase - physiology; DNA editing; HIV-1; HIV-1 - genetics; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; In Vitro Techniques; Infectious Disease; Intrinsic immunity; Minor Histocompatibility Antigens; Mutagenesis, Site-Directed; Nucleoside Deaminases - chemistry; Nucleoside Deaminases - genetics; Nucleoside Deaminases - physiology; Protein Structure, Tertiary; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - physiology; RNA Editing; RNA, Viral - genetics; RNA, Viral - metabolism; HIV-1; Intrinsic immunity; DNA editing; APOBEC3G
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2007.03.019

Abstract 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 ∼ 4-fold and ∼ 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.