- 作者: Lisa F. Rezende Yvonne Kew Vinayaka R. Prasad
- 作者服務機構: Department of Microbiblogy and Immunology, Albert Einstein College of Medicine, Bronx, N.Y., USA
- 中文摘要: --
- 英文摘要: We previously reported that two insertions of 15 aminoacids in the β3-β4 hairpin loop of fingers subdomain ofHIV-1 RT confer an increased polymerase processivi-ty. The processivity of human immunodeficiency virus(HIV) reverse transcriptase (RT) is thought to influencethe fidelity of HIV-1 RT, which tends to create errors attemplate sites with high termination probability. Em-ploying the two insertion variants of HIV-1 RT (FE20 andFE103), we examined the relationship between proces-sivity, overall fidelity and error specificity. Although theoverall mutation rate was unaffected by increased pro-cessivity, one of the mutants, FE103, generated signifi-cantly fewer frameshift errors. The other mutant, FE20,generated errors at hotspots not previously observed forHIV-1 RT. Our results indicate that an increase in thepolymerase processivity of HIV-1 RT does not necessari-ly result in a decreased mutation rate and confirm thatchanges in processivity alter the sequence context inwhich the errors are made.Furthermore, our results alsoreveal that the mutation frequency obtained via in vitrogap-filling reactions with wild-type HIV-1 RT is only2-fold higher than that obtained via a single cycle infec-tion assay using the same, wild-type HIV-1 RT se-quence as part of the helper pol function [Mansky andTemin: J Virol 69:5087-5094f1995].
- 中文關鍵字: --
- 英文關鍵字: HIV-1 reverse transcriptase. Polymerase processivity. Forward mutation rate