HIV-1 protease mutation 82M contributes to phenotypic resistance to protease inhibitors in subtype G.

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Serval ID
serval:BIB_673457981B72
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HIV-1 protease mutation 82M contributes to phenotypic resistance to protease inhibitors in subtype G.
Journal
Journal of Antimicrobial Chemotherapy
Author(s)
Palma A.C., Covens K., Snoeck J., Vandamme A.M., Camacho R.J., Van Laethem K.
ISSN
1460-2091 (Electronic)
ISSN-L
0305-7453
Publication state
Published
Issued date
2012
Volume
67
Number
5
Pages
1075-1079
Language
english
Notes
Publication types: Journal Article
Abstract
OBJECTIVES: The purpose of this study was the qualitative and quantitative assessment of the in vitro effect of HIV-1 protease (PR) mutation 82M on replication capacity and susceptibility to the eight clinically available PR inhibitors (PIs).¦METHODS: The 82M substitution was introduced by site-directed mutagenesis in wild-type subtype B and G strains, as well as reverted back to wild-type in a therapy-failing strain. The recombinant viruses were evaluated for their replication capacity and susceptibility to PIs.¦RESULTS: The single 82M mutation within a wild-type subtype B or G background did not result in drug resistance. However, the in vitro effect of single PR mutations on PI susceptibility is not always distinguishable from wild-type virus, and particular background mutations and polymorphisms are required to detect significant differences in the drug susceptibility profile. Consequently, reverting the 82M mutation back to wild-type (82I) in a subtype G isolate from a patient that failed therapy with multiple other PR mutations did result in significant increases in susceptibility towards indinavir and lopinavir and minor increases in susceptibility towards amprenavir and atazanavir. The presence of the 82M mutation also slightly decreased viral replication, whether it was in the genetic background of subtype B or subtype G.¦CONCLUSIONS: Our results suggest that 82M has an impact on PI susceptibility and that this effect is not due to a compensatory effect on the replication capacity. Because 82M is not observed as a polymorphism in any subtype, these observations support the inclusion of 82M in drug resistance interpretation systems and PI mutation lists.
Pubmed
Web of science
Open Access
Yes
Create date
05/05/2012 16:31
Last modification date
25/09/2019 7:09
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