The High Cost of Fidelity
Sarah B Lloyd, Stephen J Kent, Wendy R Winnall
AIDS RESEARCH AND HUMAN RETROVIRUSES | MARY ANN LIEBERT, INC | Published : 2014
The notoriously low fidelity of HIV-1 replication is largely responsible for the virus's rapid mutation rate, facilitating escape from immune or drug control. The error-prone activity of the viral reverse transcriptase (RT) is predicted to be the most influential mechanism for generating mutations. The low fidelity of RT has been successfully exploited by nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs) that halt viral replication upon incorporation. Consequently, drug-resistant strains have arisen in which the viral RT has an increased fidelity of replication, thus reducing analogue incorporation. Higher fidelity, however, impacts on viral fitness. The appearance ..View full abstract
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Awarded by NHMRC
We thank Dr. Con Sonza, Dr. Matthew Parsons, and Ms. Caroline Fernandez for advice on the manuscript. This work was supported by NHMRC fellowships (1013221 to W. R. W. and 1041832 to S.J.K.), the NHMRC program grant 510448, and an Early Career Researcher grant from the University of Melbourne.