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Virology. 2015 Oct;484:127-35. doi: 10.1016/j.virol.2015.05.020. Epub 2015 Jun 18.

Mutations in human immunodeficiency virus type 1 reverse transcriptase that make it sensitive to degradation by the viral protease in virions are selected against in patients.

Author information

1
HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
2
HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA. Electronic address: hughesst@mail.nih.gov.

Abstract

Mutations in the thumb subdomain of reverse transcriptase (RT) of HIV-1 can cause this enzyme to be degraded in virions by the viral protease (PR). Many of these mutations confer a temperature-sensitive phenotype on RT and viral replication. The degradation of RT by PR appears to take place after Gag-Pol has been processed. We show here that mutations in other parts of RT, including the RNase H domain, can make RT PR-sensitive and temperature-sensitive. These data explain why some mutations in the RNase H domain, which had little or no effect on the polymerase activity of purified recombinant RT, had a profound effect on viral titer. Because the PR-sensitive phenotype significantly reduced viral titer, we previously suggested that these mutations would be selected against in patients. We also show that RT mutations that are known to confer a temperature sensitive phenotype are rarely found in the Stanford database.

KEYWORDS:

Gag-Pol; HIV; Protease; RNase H; RT; Temperature sensitive

PMID:
26093496
PMCID:
PMC4887144
DOI:
10.1016/j.virol.2015.05.020
[Indexed for MEDLINE]
Free PMC Article

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