We are investigating the role of mutations in the HIV reverse transcriptase that are highly prevalent in viral isolates from drug-treated individuals on drug resistance and virological failure. This includes silent mutations (that do not code for amino acid changes) selected during drug treatment.
Our studies have led to the identification of N348I in the HIV reverse transcriptase connection domain that is prevalent in drug-treated individuals and leads to dual reverse transcriptase inhibitor class resistance.
Tachedjian G and Sluis-Cremer N. Chapter 13. Role of RNase H activity in NRTI/NNRTI Drug Resistance. pp281 – 303. Edited by Stuart LeGrice and Mattias Gotte. In Human Immunodeficiency virus reverse transcriptase: A bench-to-bedside success. Springer Publishing Company, New York. Published August 2013. ISBN 978-1-4614-7290-2
- Increasing Prevalence of Synonymous Mutations K65K and K66K in HIV-1 subtype B reverse transcriptase.
Telwatte S, Brumme CJ, Hearps AC, Latham CF, Hayward JA, Sonza S, Sluis-Cremer N, Harrigan PR, Tachedjian G
AIDS. 2016 Sep; 30(18):2787-2793
- High fidelity simian immunodeficiency virus reverse transcriptase mutants have impaired replication in vitro and in vivo.
Lloyd SB, Lichtfuss M, Amarasena TH, Alcantara S, De Rose R, Tachedjian G, Alinejad-Rokny H, Venturi V, Davenport MP, Winnall WR, Kent SJ
Virology. 2016 Feb; 492:1-10
- Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations.
Telwatte S, Hearps AC, Johnson A, Latham CF, Moore K, Agius P, Tachedjian M, Sonza S, Sluis-Cremer N, Harrigan PR, Tachedjian G
Nucleic Acids Res. 2015 Mar; Epub ahead of print
- N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance.
Yap SH, Sheen CW, Fahey J, Zanin M, Tyssen D, Lima VD, Wynhoven B, Kuiper M, Sluis-Cremer N, Harrigan PR, Tachedjian G
PLoS Med. 2007 Dec; 4(12):e335