Cytidine deamination of retroviral DNA by diverse APOBEC proteins.
The human cytidine deaminase APOBEC3G edits both nascent human immunodeficiency virus (HIV) and murine leukemia virus (MLV) reverse transcripts, resulting in loss of infectivity. The HIV Vif protein is able to protect both viruses from this innate restriction to infection. Here, we demonstrate that a number of other APOBEC family members from both humans and rodents can mediate anti-HIV effects, through cytidine deamination. Three of these, rat APOBEC1, mouse APOBEC3, and human APOBEC3B, are able to inhibit HIV infectivity even in the presence of Vif. Like APOBEC3G, human APOBEC3F preferentially restricts vif-deficient virus. Indeed, the mutation spectra and expression profile found for APOBEC3F indicate that this enzyme, together with APOBEC3G, accounts for the G to A hypermutation of proviruses described in HIV-infected individuals. Surprisingly, although MLV infectivity is acutely reduced by APOBEC3G, no other family member tested here had this effect. It is especially interesting that although both rodent APOBECs markedly diminish wild-type HIV infectivity, MLV is resistant to these proteins. This implies that MLV may have evolved to avoid deamination by mouse APOBEC3. Overall, our findings show that although APOBEC family members are highly related, they exhibit significantly distinct antiviral characteristics that may provide new insights into host-pathogen interactions.
Department of Infectious Diseases, Guy's, King's and St Thomas' School of Medicine, King's College London, London, SE1 9RT, United Kingdom.
Kate N
KN
Bishop
Rebecca K
RK
Holmes
Ann M
AM
Sheehy
Nicholas O
NO
Davidson
Soo-Jin
SJ
Cho
Michael H
MH
Malim
D000071479:APOBEC-1 Deaminase; D000998:Antiviral Agents / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000378:metabolism*; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D016341:Genes, vif / Q000235:genetics*; D006678:HIV / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D015151:Immunoblotting; D009052:Leukemia Virus, Murine / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D017422:Sequence Analysis, DNA
D000998:Antiviral Agents; D001055:Apolipoproteins B; D017931:DNA Primers; D018076:DNA, Complementary; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; C000605091:Apobec1 protein, rat; D003564:Cytidine Deaminase