title: The M184V mutation in reverse transcriptase can delay reversion of attenuated variants of simian immunodeficiency virus.
abstract: We previously constructed a series of simian immunodeficiency virus (SIV) mutants containing deletions within a 97-nucleotide region of the SIVmac239 untranslated region or leader sequence. However, as is common with live attenuated viruses, several of the mutants exhibited a moderate propensity for reversion. Since the M184V mutation in human immunodeficiency virus type 1 reverse transcriptase is associated with diminished fitness as well as lamivudine resistance, we introduced this substitution into several of our deletion mutants to determine its effects on viral replication and compensatory reversion. Our results indicate that M184V impaired viral fitness in pair-wise comparisons of mutants that contained or lacked this substitution. We also observed that M184V significantly impaired the potential for both compensatory mutagenesis and reversion in these mutants both in cell lines and in peripheral blood mononuclear cells.
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2.
authors.forename: James B
authors.initials: JB
authors.lastname: Whitney
authors.forename: Maureen
authors.initials: M
authors.lastname: Oliveira
authors.forename: Mervi
authors.initials: M
authors.lastname: Detorio
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Guan
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D019281:Dimerization; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008253:Macaca mulatta; D009154:Mutation; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase