title: Isolation and characterization of simian immunodeficiency virus variants that are resistant to nonnucleoside reverse transcriptase inhibitors.
abstract: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) act quite specifically on human immunodeficiency virus type 1 (HIV-1). In general, they are not effective on human immunodeficiency virus type 2 (HIV-2) or simian immunodeficiency virus (SIV). Only SIV strains from African green monkeys are sensitive to several NNRTIs. Here we isolated NNRTI- and 3TC-resistant SIVagm variants. Viruses resistant to delavirdine contained V112I and M231I substitutions, while those resistant to 3TC contained a M 185I substitution. These amino acids are highly conserved in HIV-1, HIV-2, SIVmac and SIVagm, and the M184I (M185I in SIVagm) substitution was observed in 3TC-resistant HIV-1 and SIVmac. The roles of the observed mutations in NNRTI-resistance of SIVagm and HIV-1 were further confirmed by site-directed mutagenesis. The present results have provided a new insight into the common mechanism of sensitivity of HIV- 1 and SIVagm to NNRTIs.
authors.affiliation: Discovery Research Laboratories, Shionogi & Co. Ltd., Osaka, Japan
authors.forename: Y
authors.initials: Y
authors.lastname: Isaka
authors.forename: S
authors.initials: S
authors.lastname: Miki
authors.forename: S
authors.initials: S
authors.lastname: Kawauchi
authors.forename: A
authors.initials: A
authors.lastname: Suyama
authors.forename: H
authors.initials: H
authors.lastname: Sugimoto
authors.forename: A
authors.initials: A
authors.lastname: Adachi
authors.forename: M
authors.initials: M
authors.lastname: Hayami
authors.forename: O
authors.initials: O
authors.lastname: Yoshie
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.forename: A
authors.initials: A
authors.lastname: Sato
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D020008:Delavirdine / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D006367:HeLa Cells; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008969:Molecular Sequence Data; D017354:Point Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D016415:Sequence Alignment; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D013329:Structure-Activity Relationship
chemical_list: D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D020008:Delavirdine