Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Two mutant virus strains in which the novel P225H mutation appeared in a V106A reverse transcriptase (RT)-mutated genetic background upon treatment of human immunodeficiency virus type 1 (HIV-1) with quinoxaline S-2720 were isolated. Surprisingly, the addition of the P225H mutation to the V106A RT mutant genetic background resensitized the V106A RT mutant virus to the non-nucleoside RT inhibitor (NNRTI) BHAP U-90152, but not to other NNRTIs. Construction of both recombinant viruses and recombinant RTs containing the V106A, P225H and V106A+P225H mutations revealed that P225H was indeed responsible for the marked potentiation of the antiviral activity of BHAP against the P225H single-mutant virus and the V106A+P225H double-mutant virus when compared to wild-type and V106A single-mutant viruses, respectively. An explanation for the markedly increased sensitivity of the P225H mutant HIV-1 RT to BHAP and not to the other NNRTIs was provided by the unique features of the X-ray structure of the RT-BHAP complex.

Original publication

DOI

10.1099/0022-1317-79-6-1347

Type

Journal article

Journal

The Journal of general virology

Publication Date

06/1998

Volume

79 ( Pt 6)

Pages

1347 - 1352

Addresses

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

Keywords

Humans, HIV-1, Delavirdine, Histidine, Proline, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Amino Acid Substitution, HIV Reverse Transcriptase