In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 43, No. 10 ( 1999-10), p. 2479-2483
Abstract:
Two methylenecyclopropane nucleoside analogues with a phenylphosphoralaninate moiety, QYL-685 and QYL-609, exert potent and specific activities against human immunodeficiency virus type 1 strain LAI (HIV-1 LAI ) and HIV-2 in vitro. In this study, we induced HIV-1 variants resistant to QYL-685 by exposing HIV-1 LAI to increasing concentrations of QYL-685. After 16 passages, the virus (HIV-1 P16 ) was less sensitive to QYL-685 (104-fold), QYL-609 ( 〉 41-fold), and (−)-β-2′,3′-dideoxy-3′-thiacytidine (3TC) ( 〉 1,100-fold) than was HIV-1 LAI and contained an M184I mutation. Two infectious clones, HIV-1 M184I and HIV-1 M184V , were resistant to QYL-685, QYL-609, and 3TC, confirming that the M184I mutation was responsible for the observed resistance. Viral-fitness analyses (competitive HIV-1 replication assays) revealed that in the absence of drugs, M184I and M184V conferred a replication disadvantage on the virus compared to the replication efficiency of the wild-type infectious clone (HIV-1 wt ). However, in the presence of QYL-685 (4 μM), HIV-1 M184I and HIV-1 M184V showed greater fitness than HIV-1 wt . These data may provide structural and virological relevance with regard to the emergence of M184I and M184V substitutions in HIV-1.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.43.10.2479
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
1999
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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