Template usage is responsible for the preferential acquisition of the K65R reverse transcriptase mutation in subtype C variants of human immunodeficiency virus type 1

McGill University AIDS Center, McGill University, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, Canada.
Journal of Virology (Impact Factor: 4.65). 01/2009; 83(4):2029-33. DOI: 10.1128/JVI.01349-08
Source: PubMed

ABSTRACT We propose that a nucleotide template-based mechanism facilitates the acquisition of the K65R mutation in subtype C human immunodeficiency virus type 1 (HIV-1). Different patterns of DNA synthesis were observed using DNA templates from viruses of subtype B or C origin. When subtype C reverse transcriptase (RT) was employed to synthesize DNA from subtype C DNA templates, preferential pausing was seen at the nucleotide position responsible for the AAG-to-AGG K65R mutation. This did not occur when the subtype B RT and template were used. Template factors can therefore increase the probability of K65R development in subtype C HIV-1.

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Available from: Daniela Moisi, Jun 24, 2014
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    • "Subtype C viruses apparently have an intrinsic difficulty in synthesizing stretches of adenine homopolymeric runs that leads to template pausing at codon 65, facilitating the acquisition of K65R under selective drug pressure [37] [38], whereas the subtype B template favors pausing at codon 67 that may facilitate the generation of D67N and TAMs rather than K65R [37] [38] [39]. In addition, the introduction of codons from positions 64 and 65 in the RT of subtype C into a subtype B backbone was sufficient to lead to selection of K65R by multiple NRTIs [37] [38] [39]. Figure 1 provides a pictorial representation of the preferential development of K65R in subtype C viruses. "
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