title: Impact of the N348I mutation in HIV-1 reverse transcriptase on nonnucleoside reverse transcriptase inhibitor resistance in non-subtype B HIV-1.
abstract: We investigated the effect of N348I alone and with M184V on nonnucleoside reverse transcriptase inhibitor (NNRTI) drug susceptibility and replicative capacity in B and non-B HIV-1 isolates. N348I reduced the susceptibility to all NNRTI drugs across subtypes. The replication capacity of all viruses in a variety of cell lines was impaired by N348I. Interestingly, the N348I and M184V double mutation compensated for the reduced NNRTI drug susceptibility observed in the N348I single mutant and marginally improved viral replicative capacity.
authors.affiliation: Centre of Virology, Royal Free and University College London Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom. a.mccormick@medsch.ucl.ac.uk
authors.forename: Adele L
authors.initials: AL
authors.lastname: McCormick
authors.forename: Chris M
authors.initials: CM
authors.lastname: Parry
authors.forename: Anne
authors.initials: A
authors.lastname: Crombe
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Goodall
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Gupta
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
authors.forename: Michael
authors.initials: M
authors.lastname: Chirara
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Towers
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
mesh_terms: D000480:Alkynes; D019943:Amino Acid Substitution; D048588:Benzoxazines / Q000494:pharmacology; D002460:Cell Line; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics*; D057809:HEK293 Cells; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology; D009570:Nitriles; D011724:Pyridazines / Q000494:pharmacology; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D019829:Nevirapine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C098320:efavirenz