title: Disruption of the putative splice acceptor site for SIV(mac239)Vif reveals tight control of SIV splicing and impaired replication in Vif non-permissive cells.
abstract: Vif is dispensable for simian immunodeficiency virus (SIV) replication in some cells, termed permissive (i.e., CEM-SS), but not in others, termed non-permissive (i.e., H9, CEMx174, and peripheral blood lymphocytes). Non-permissive cells express the RNA editing enzyme, APOBEC3G. To determine whether vif mRNA could be alternatively spliced, a mutation altering the putative vif splice acceptor site (SA1) was introduced into SIV(mac239) (SIV(Deltavif-SA)). Despite three consensus splice acceptor sites nearby SA1, SIV(Deltavif-SA) did not efficiently generate alternatively spliced vif mRNA. SIV(Deltavif-SA) was growth attenuated in CEMx174 and H9 cells but not in CEM-SS cells. Following SIV(Deltavif-SA), but not SIV(mac239), infection in either H9 or CEMx174 cells viral cDNA contained numerous G to A mutations; no such differences were observed in CEM-SS cells. This pattern is consistent with mutations generated by APOBEC3G in the absence of Vif. Therefore, efficient splicing of SIV vif mRNA is tightly controlled and requires the SA1 site.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4800, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Victoria
authors.forename: W Edward
authors.initials: WE
authors.lastname: Robinson
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D016384:Consensus Sequence; D004261:DNA Replication; D016346:Gene Products, vif / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D016346:Gene Products, vif; D012333:RNA, Messenger; D012367:RNA, Viral