Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Brenner, B. et al.

A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors.

OBJECTIVE: We have shown that HIV-1 clade C variants contain a valine codon 106 polymorphism ( GTG) that facilitates a V106M transition (GTG<--ATG) after selection with efavirenz (EFV). This study evaluates the prevalence of V106 ( GTG) and 106M (ATG) codons in clinical isolates as well as the effects of V106M on resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). METHODS: Genotypic analysis ascertained sequence diversity at codon 106, including both valine polymorphisms ( GTA and GTG) and the V106A ( GCA) and V106M (ATG) resistance-conferring mutations in B (n = 440) and non-B (n = 84) clinical isolates. Cell-based phenotypic assays were performed to determine the effects of V106M and V106A on levels of resistance to EFV, nevirapine and delavirdine. RESULTS: Most subtype B isolates harbored GTA (valine) at codon 106 (97% of cases) while the GTG (valine) polymorphism was generally present in clade C viruses (94% of cases). Under conditions of EFV but not nevirapine or delavirdine pressure (n = 8) in tissue culture, clade C isolates developed the V106M mutation (GTG<--ATG), conferring high-level (100-1000-fold) cross-resistance to all NNRTI. Generation of V106M recombinant viruses by site-directed mutagenesis confirmed the ability of V106M to confer NNRTI cross-resistance. This mutation also developed in three of six EFV-treated patients harboring clade C infections. In current genotypic interpretative reports (including 15 algorithmic databases), V106A is listed as an nevirapine-specific mutation while V106M is not recognized. CONCLUSIONS: V106M may be a signature mutation in clade C patients treated with EFV and may have the potential to confer high-level multi-NNRTI resistance.[1]

References

A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors. Brenner, B., Turner, D., Oliveira, M., Moisi, D., Detorio, M., Carobene, M., Marlink, R.G., Schapiro, J., Roger, M., Wainberg, M.A. AIDS (2003) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.