Nucleic Acids Res 2015 Mar 12;43(6):3256-71. Epub 2015 Mar 12.
Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia Department of Infectious Diseases, Monash University, Melbourne, Victoria 3004, Australia Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia
Resistance to combined antiretroviral therapy (cART) in HIV-1-infected individuals is typically due to nonsynonymous mutations that change the protein sequence; however, the selection of synonymous or 'silent' mutations in the HIV-1 genome with cART has been reported. These silent K65K and K66K mutations in the HIV-1 reverse transcriptase (RT) occur in over 35% of drug-experienced individuals and are highly associated with the thymidine analog mutations D67N and K70R, which confer decreased susceptibility to most nucleoside and nucleotide RT inhibitors. However, the basis for selection of these silent mutations under selective drug pressure is unknown. Read More