TY - JOUR
T1 - Antiretroviral drug resistance in HIV-2
T2 - three amino acid changes are sufficient for classwide nucleoside analogue resistance
AU - Smith, Robert A.
AU - Anderson, Donovan J.
AU - Pyrak, Crystal L.
AU - Preston, Bradley D.
AU - Gottlieb, Geoffrey S.
N1 - Funding Information:
Received 12 July 2008; accepted 4 November 2008; electronically published 8 April 2009. Potential conflicts of interest: none reported. Presented in part: Cold Spring Harbor Laboratory Retroviruses Meeting, Cold Spring Harbor, New York, 19–24 May 2008 (abstract 263). Financial support: Public Health Service (grants R01 AI060466 to G.S.G. and R01 AI34834 to B.D.P); Mary Gates Endowment (undergraduate research grant to C.L.P.). Reprints or correspondence: Dr. Robert A. Smith, University of Washington, Dept. of Pathology, Box 357705, 1959 NE Pacific St., Seattle WA 98133 (smithra@u.washington.edu). TheJournalofInfectiousDiseases 2009;199:1323–6 © 2009 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2009/19909-0013$15.00 DOI: 10.1086/597802
PY - 2009/5/1
Y1 - 2009/5/1
N2 - Genotypic surveys suggest that human immunodeficiency virus type 1 (HIV-1) and HIV-2 evolve different sets of mutations in response to nucleoside reverse-transcriptase inhibitors (NRTIs). We used site-directed mutagenesis, culturebased phenotyping, and cell-free assays to determine the resistance profiles conferred by specific amino acid replacements in HIV-2 reverse transcriptase. Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with K65R or M184V was sufficient for high-level resistance to both lamivudine and zidovudine in HIV-2, and the combination of K65R, Q151M, and M184V conferred classwide NRTI resistance. These data suggest that current NRTI-based regimens are suboptimal for treating HIV-2 infection.
AB - Genotypic surveys suggest that human immunodeficiency virus type 1 (HIV-1) and HIV-2 evolve different sets of mutations in response to nucleoside reverse-transcriptase inhibitors (NRTIs). We used site-directed mutagenesis, culturebased phenotyping, and cell-free assays to determine the resistance profiles conferred by specific amino acid replacements in HIV-2 reverse transcriptase. Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with K65R or M184V was sufficient for high-level resistance to both lamivudine and zidovudine in HIV-2, and the combination of K65R, Q151M, and M184V conferred classwide NRTI resistance. These data suggest that current NRTI-based regimens are suboptimal for treating HIV-2 infection.
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U2 - 10.1086/597802
DO - 10.1086/597802
M3 - Article
C2 - 19358668
AN - SCOPUS:65649146417
SN - 0022-1899
VL - 199
SP - 1323
EP - 1326
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -