Exploitation of the low fidelity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the nucleotide composition bias in the HIV-1 genome to alter the drug resistance development of HIV.

摘要: The RNA genome of the lentivirus human immunodeficiency virus type 1 (HIV-1) is significantly richer in adenine nucleotides than statistically equal distribution four different that expected. This compositional bias may be due to guanine-to-adenine (G3A) nucleotide hypermutation HIV genome, which has been explained by dCTP pool imbalances during reverse transcription. together with poor fidelity HIV-1 transcriptase markedly enhances genetic variation and responsible for rapid emergence drug-resistant strains. We have now attempted counteract normal mutational pattern response anti-HIV-1 drugs altering endogenous deoxynucleoside triphosphate ratios antimetabolites virus-infected cell cultures. showed administration these antimetabolic compounds resulted an altered drug resistance reversal predominant flow adenine-to-guanine (A3G) intact HIV-1-infected lymphocyte Forcing change its inherent lead better control viral development.