High fidelity simian immunodeficiency virus reverse transcriptase mutants have impaired replication in vitro and in vivo
Sarah B Lloyd, Marit Lichtfuss, Thakshila H Amarasena, Sheilajen Alcantara, Robert De Rose, Gilda Tachedjian, Hamid Alinejad-Rokny, Vanessa Venturi, Miles P Davenport, Wendy R Winnall, Stephen J Kent
VIROLOGY | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2016
The low fidelity of HIV replication facilitates immune and drug escape. Some reverse transcriptase (RT) inhibitor drug-resistance mutations increase RT fidelity in biochemical assays but their effect during viral replication is unclear. We investigated the effect of RT mutations K65R, Q151N and V148I on SIV replication and fidelity in vitro, along with SIV replication in pigtailed macaques. SIVmac239-K65R and SIVmac239-V148I viruses had reduced replication capacity compared to wild-type SIVmac239. Direct virus competition assays demonstrated a rank order of wild-type>K65R>V148I mutants in terms of viral fitness. In single round in vitro-replication assays, SIVmac239-K65R demonstrated signifi..View full abstract
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Awarded by Australian NHMRC Fellowships
Awarded by NHMRC Program
We thank Dr. Robert Center, Prof Damian Purcell and Dr. Keith Peden for SIV reagents and Sushama Telwatte for expert advice. This work was supported by Australian NHMRC Fellowships (1013221 to WRW and 1041832 to SJK), NHMRC Program grant 510448 and an Early Career Researcher grant from the University of Melbourne.