Vpr.A3A chimera inhibits HIV replication.
Several APOBEC3 proteins (A3F and A3G), that are cytidine deaminases restrict human immunodeficiency virus (HIV) replication in the absence of the viral infectivity factor (Vif) protein. However, Vif leads to their degradation and counteracts their effects. Another member, A3A, restricts some retrotransposons and another virus but not HIV. We reasoned that this failure was due to the lack of appropriate targeting. Thus, we fused A3A to another viral protein, Vpr, which binds p6 in Gag and is incorporated into viral cores. Indeed, the Vpr.A3A chimera but not A3A was found abundantly in the viral core. It also restricted potently the replication of HIV and simian immunodeficiency virus in the presence and absence of Vif. Because we identified a high frequency of G to A mutations in viral cDNAs, this antiviral activity was mediated by DNA editing. Interestingly, our fusion protein did not restrict murine leukemia virus, which does not incorporate Vpr. Thus, by targeting appropriately a potent single domain cytidine deaminase, we rendered HIV and simian immunodeficiency virus restriction resistant to Vif.
Department of Medicine, Microbiology, and Immunology, University of California at San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143-0703, USA.
Renato S
RS
Aguiar
Nika
N
Lovsin
Amilcar
A
Tanuri
B Matija
BM
Peterlin
D001483:Base Sequence; D002460:Cell Line; D003564:Cytidine Deaminase; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D016346:Gene Products, vif / Q000235:genetics / Q000502:physiology; D006678:HIV / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000502:physiology; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D004279:DNA, Viral; D016346:Gene Products, vif; D011506:Proteins; D011993:Recombinant Fusion Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase