Identification of APOBEC3DE as another antiretroviral factor from the human APOBEC family.
A tandem arrayed gene cluster encoding seven cytidine deaminase genes is present on human chromosome 22. These are APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3DE, APOBEC3F, APOBEC3G, and APOBEC3H. Three of them, APOBEC3G, APOBEC3F, and APOBEC3B, block replication of human immunodeficiency virus type 1 (HIV-1) and many other retroviruses. In addition, APOBEC3A and APOBEC3C block intracellular retrotransposons and simian immunodeficiency virus (SIV), respectively. In opposition to APOBEC genes, HIV-1 and SIV contain a virion infectivity factor (Vif) that targets APOBEC3F and APOBEC3G for polyubiquitylation and proteasomal degradation. Herein, we studied the antiretroviral activities of the human APOBEC3DE and APOBEC3H. We found that only APOBEC3DE had antiretroviral activity for HIV-1 or SIV and that Vif suppressed this antiviral activity. APOBEC3DE was encapsidated and capable of deaminating cytosines to uracils on viral minus-strand DNA, resulting in disruption of the viral life cycle. Other than GG-to-AG and AG-to-AA mutations, it had a novel target site specificity, resulting in introduction of GC-to-AC mutations on viral plus-strand DNA. Such mutations have been detected previously in HIV-1 clinical isolates. In addition, APOBEC3DE was expressed much more extensively than APOBEC3F in various human tissues and it formed heteromultimers with APOBEC3F or APOBEC3G in the cell. From these studies, we concluded that APOBEC3DE is a new contributor to the intracellular defense network, resulting in suppression of retroviral invasion.
Dang
Ying
Y
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824-4320, USA.
Wang
Xiaojun
X
Esselman
Walter J
WJ
Zheng
Yong-Hui
YH
D000071478:APOBEC Deaminases; D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000378:metabolism; D044966:Anti-Retroviral Agents / Q000378:metabolism*; D002460:Cell Line; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics* / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D016346:Gene Products, vif / Q000502:physiology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family; D017354:Point Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000472:pathogenicity; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D018076:DNA, Complementary; D004279:DNA, Viral; D016346:Gene Products, vif; D012333:RNA, Messenger; D054320:vif Gene Products, Human Immunodeficiency Virus; D046988:Proteasome Endopeptidase Complex; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase