Relative Fitness and Replication Capacity of a Multinucleoside Analogue-Resistant Clinical Human Immunodeficiency Virus Type 1 Isolate with a Deletion of Codon 69 in the Reverse Transcriptase Coding Region

摘要: Deletions, insertions, and amino acid substitutions in the β3-β4 hairpin loop-coding region of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have been associated with resistance to nucleoside RT inhibitors when appearing combination other mutations RT-coding region. In this work, we measured vivo fitness HIV-1 variants containing a deletion 3 nucleotides affecting codon 69 (Δ69) viral as well replication capacity (RC) ex series recombinant carrying an bearing Δ69 or T69A mutation multidrug-resistant (MDR) sequence background, including Q151M complex M184V, K103N, Y181C, G190A. Patient-derived clones having RTs together S163I showed increased RCs under drug pressure. These data were consistent population dynamics observed long-term-treated HIV-1-infected patient. absence drugs, replicated more efficiently than those Δ69, but only patient-derived sequences corresponding residues 248 527 present. effects could be attributed functional interaction between C-terminal domain p66 subunit (RNase H domain) DNA polymerase RT. Finally, MDR-associated mutations, deletions at 69, susceptibilities protease phenotypic assays. correlated impaired Gag cleavage delayed maturation decreased production active variants.