Effects of Nucleoside Analogs on Native and Site-Directed Mutants of HTLV Type 1 Reverse Transcriptase

✍ Scribed by Vivek Anantharaman; Laura K. Moen

• Book ID: 102966073
• Publisher: Elsevier Science
• Year: 2000
• Tongue: English
• Weight: 588 KB
• Volume: 28
• Category: Article
• ISSN: 0045-2068
• DOI: 10.1006/bioo.2000.1181

✦ Synopsis

A bacterial assay was developed for testing HTLV-1 reverse transcriptase sensitivity to common nucleoside analog inhibitors in an Escherichia coli strain characterized by a temperature sensitive PolI/RecA deletion phenotype. This genetic complementation assay exploits the ability of HTLV-1 reverse transcriptase to functionally replace these missing activities at nonpermissive temperatures. The four inhibitors tested, dideoxyinosine, dideoxyadenosine, deoxythymidine, and didehydrodeoxythymidine are well-known inhibitors of HIV reverse transcriptase. All except dideoxyadenosine showed a strong activity against HTLV-1 reverse transcriptase with IC(50); in the nanomolar range. Sequence alignments were used to identify amino acid residues in HTLV-1 reverse transcriptase, which correspond to those identified as important for drug-resistance in HIV reverse transcriptase. Mutations of some of these HTLV-1 residues altered the IC(50) for the inhibitors as expected, which suggests that these amino acids have a function in HTLV-1 reverse transcriptase similar to that of their homologs in HIV reverse transcriptase. Copyright 2000 Academic Press.