Analysis of amino insertion mutations in the fingers subdomain of HIV-1 reverse transcriptase.
In response to dideoxy inosine/hydroxyurea dual therapy, HIV-1 (human immunodeficiency virus type-1) variants were isolated that had a small amino acid insertion and flanking amino acid substitutions in the fingers subdomain of HIV-1. We have analyzed the reverse transcriptase variants for their effects on HIV-1 reverse transcriptase activity. The data suggests that the inserted amino acid residues are responsible for low-level resistance to the nucleoside analog ddITP, while the role of the flanking amino acid substitutions is to compensate for the deleterious effects of the insertion.
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD, 21702-1201, USA.
P L
PL
Boyer
J
J
Lisziewicz
F
F
Lori
S H
SH
Hughes
D019380:Anti-HIV Agents / Q000494:pharmacology; D003838:Deoxyadenine Nucleotides / Q000494:pharmacology; D016049:Didanosine / Q000494:pharmacology; D054306:Dideoxynucleotides; D004352:Drug Resistance, Microbial / Q000235:genetics; D015658:HIV Infections / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D016254:Mutagenesis, Insertional; D011487:Protein Conformation
D019380:Anti-HIV Agents; D003838:Deoxyadenine Nucleotides; D054306:Dideoxynucleotides; C037773:2',3'-dideoxyadenosine triphosphate; D054303:HIV Reverse Transcriptase; D016049:Didanosine