Impact of nucleotide polymorphisms at drug resistance sites on genetic barrier in human immunodeficiency virus type 1 subtype C resistance evolution

Abstract

Genetic diversity is the hallmark of human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome (AIDS). This diversity has resulted in a spectrum of different subtypes within the group M viruses that is responsible for the AIDS pandemic. Nucleotide substitutions and polymorphisms at codons known to confer drug resistance in subtype B viruses were compared with similar substitutions in subtype C viruses. Genetic barrier was determined on viruses isolated from drug naive patients infected with subtype C viruses. We found a reduced genetic barrier in subtype C viruses at codon V106M (GTA to ATG) and an increased barrier at codon L210W (TTA/CTG/CTA to TGG) when compared to subtype B consensus. The highest genetic barrier in subtype C viruses is found at codon Q151M where two transversions or each one of transition and transversion are needed for the resistance evolution.

Key words: Human immunodeficiency virus (HIV), drug resistance, genetic barrier, non-B subtypes.