title: Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase.
abstract: OBJECTIVE
  The amino acid position 70 in HIV-1 reverse transcriptase (RT) plays an important role in nucleoside RT inhibitor (NRTI) resistance. K70R is part of the thymidine analog mutations, but also other amino acid changes have been associated with NRTI resistance, such as K70E and K70G. In this study, we investigated the in vivo selection of the HIV-1 RT mutations K70S and K70T and their in vitro effect on drug resistance and replication capacity.
  
  
  METHODS
  Recombinant viruses with RT mutations were generated to measure the in vitro drug susceptibility and replication capacity. Bayesian network analysis and three-dimensional modeling were performed to understand the selection and impact of the RT70 mutations.
  
  
  RESULTS
  K70S and K70T were found at a low frequency in RTI-experienced HIV-1 patients (0.10% and 0·20%). Baeyesian network learning identified no direct association with the in vivo exposure to any specific RTI. However, direct associations of K70S with mutations within the Q151M-complex and of K70T with K65R were observed. In vitro phenotypic testing revealed only minor effects of K70R/S/T as single mutations, associated with Q151M and within the context of the Q151M-complex.
  
  
  CONCLUSIONS
  These results suggest that the selection of K70S/T and their phenotypic impact are influenced by the presence of other mutations in RT. However, the low impact on in vitro phenotype here observed, alongside with the low in vivo prevalence, the exclusive direct association with known major RTI mutations and the unknown correlation with in vivo response, do not yet necessitate the inclusion of K70S/T in drug resistance interpretation systems.
authors.forename: S
authors.initials: S
authors.lastname: Megens
authors.forename: S
authors.initials: S
authors.lastname: De Wit
authors.forename: J
authors.initials: J
authors.lastname: Bernatchez
authors.forename: N
authors.initials: N
authors.lastname: Dekeersmaeker
authors.forename: L
authors.initials: L
authors.lastname: Vinken
authors.forename: K
authors.initials: K
authors.lastname: Covens
authors.forename: K
authors.initials: K
authors.lastname: Theys
authors.forename: R J
authors.initials: RJ
authors.lastname: Camacho
authors.forename: A-M
authors.initials: AM
authors.lastname: Vandamme
authors.forename: M
authors.initials: M
authors.lastname: Götte
authors.forename: K
authors.initials: K
authors.lastname: Van Laethem
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D001499:Bayes Theorem; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D057809:HEK293 Cells; D015658:HIV Infections / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009154:Mutation / Q000187:drug effects / Q000235:genetics
chemical_list: D000596:Amino Acids; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: HIV-1,; Mutation,; Resistance,; Reverse transcriptase