Limiting deoxynucleoside triphosphate concentrations emphasize the processivity defect of lamivudine-resistant variants of human immunodeficiency virus type 1 reverse transcriptase.

摘要: The nucleoside drug lamivudine (3TC) triggers the selection of resistant forms human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) with a substitution amino acid 184Met. 3TC-resistant RT enzymes 184Val and 184Ile exhibit processivity defect in vitro assays that correlates reduced replication corresponding variants primary cells. However, no is apparent for these two mutants transformed T-cell line SupT1. One obvious difference between cell types intracellular deoxynucleoside triphosphate (dNTP) level. Primary cells have much smaller dNTP pool, this cellular condition may emphasize codon 184 variants. Alternatively, cell-specific cofactors influence process transcription exist. Such accessory factors be packaged into virion to exert an effect on enzyme. To discriminate possibilities we performed additional wild-type mutant enzymes. proteins were either isolated from virions produced by or expressed as recombinant protein. We also infection treated reduces pool. Furthermore, was studied within particles endogenous assay, which allows manipulation combined results indicate enzymatic HIV-1 stressed at low concentrations.