Abstract
The human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2) reverse transcriptases (RTs) are evolutionary related. To study the effect of homologous sequence replacements on polymerase function and to map the determinants of the lack of susceptibility of HIV-2 RT to nonnucleoside drugs, a series of chimeric HIV-1/HIV-2 RTs were constructed. Analysis of the chimeric RTs showed that wild-type levels of RNA-dependent DNA polymerase activity were retained when both finger and palm subdomains were exchanged as a unit between the two parental RTs. Analysis of enzymatically active chimeras for inhibition by the thiobenzimidazolone derivative TIBO R82150 showed that a segment of HIV-2 RT at 212-250, when placed in the HIV-1 RT context, conferred a 40-fold decrease in susceptibility to TIBO R82150. Site- directed mutagenesis of this segment found Tyr227 to be a key residue in this segment for the natural resistance of HIV-2 RT to TIBO R82150.
Original language | English (US) |
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Pages (from-to) | 326-333 |
Number of pages | 8 |
Journal | Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology |
Volume | 11 |
Issue number | 4 |
DOIs | |
State | Published - 1996 |
Keywords
- Chimeric reverse transcriptases
- Nonnucleoside reverse transcriptase inhibitor resistance
- Structure-function
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Virology