title: Effect of mutations in rev gene of SIVmac on virus replication.
abstract: The functional activity of SIVmac251 Rev was altered by introducing amino acid changes inside and chain termination mutations after the Rev response element-binding region (RBR) of the protein. The effects of specific mutations were evaluated by transfecting proviral DNAs into the HeLa cell line and into HeLa cells constitutively expressing either HIV-1 Rev or HTLV-1 Rex proteins. Cell-free supernatants from these transient expression assays were further characterized by infecting CD4-positive lymphoid cell lines H9 and MT-4, the latter abortively infected with HTLV-1, and human peripheral blood mononuclear cells. These results together with the data from cotransfection experiments show that SIV can be attenuated up to 95% by introducing changes into the arginine-rich domain, RBR, of Rev. These recessive mutations were efficiently complemented in trans by HIV-1 Rev, SIV Rev, and HTLV-I Rex proteins. In contrast, the mutants of Rev protein that had a chain termination after RBR were trans-dominant negative and could not be trans-complemented with any of these three regulatory proteins. When additional mutations were inserted into the RBR of these trans-dominantly negative Rev proteins, complementation was obtained again.
authors.affiliation: Institute of Biomedical Sciences, University of Tampere, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Aavik
authors.forename: K
authors.initials: K
authors.lastname: Hakkarainen
authors.forename: K J
authors.initials: KJ
authors.lastname: Krohn
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D015694:Gene Products, rev / Q000235:genetics; D015757:Genes, rev; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D018449:SAIDS Vaccines / Q000302:isolation & purification; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D014613:Vaccines, Attenuated / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000302:isolation & purification; D014779:Virus Replication / Q000235:genetics*
chemical_list: D015694:Gene Products, rev; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic