Rare one and two amino acid inserts adjacent to codon 103 of the HIV-1 reverse transcriptase (RT) affect susceptibility to non-nucleoside RT inhibitors.

Autor: Winters MA; Center for AIDS Research, Stanford University, Stanford, CA, USA. mark.winters@stanford.edu, Kagan RM, Kovari L, Heseltine PN, Merigan TC
Jazyk: angličtina
Zdroj: Antiviral therapy [Antivir Ther] 2005; Vol. 10 (2), pp. 363-6.
Abstrakt: HIV-1 strains that possess a one or two amino acid insert between codons 102 and 103 of the reverse transcriptase (RT) gene were identified in three HIV-1-infected individuals. Each strain also had one or more known mutations associated with nucleoside RT inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs). Recombinant viruses from these strains had reduced susceptibility to efavirenz and nevirapine, and homology modelling predicted a loss of binding contacts with efavirenz. Mutagenesis studies indicated that replication of insert-containing strains was dependent on RT gene mutations and polymorphisms that co-evolved with the insert. These results suggest that inserts in the NNRTI-binding pocket contribute to NNRTI resistance, but are tolerated only under specific genetic conditions.
Databáze: MEDLINE