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- Title
Isolation and characterization of simian immunodeficiency virus variants that are resistant to nonnucleoside reverse transcriptase inhibitors.
- Authors
Isaka, Y.; Miki, S.; Kawauchi, S.; Suyama, A.; Sugimoto, H.; Adachi, A.; Hayami, M.; Yoshie, O.; Fujiwara, T.; Sato, A.
- Abstract
Summary. 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 M185I 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.
- Subjects
HIV; PRIMATE diseases; NUCLEOSIDES; CHEMICAL inhibitors; AMINO acids; NATURAL immunity; GENETIC mutation; MUTAGENESIS
- Publication
Archives of Virology, 2000, Vol 145, Issue 12, p2481
- ISSN
0304-8608
- Publication type
Article
- DOI
10.1007/s007050070003