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.

FIG. 1.

NNRTI drug susceptibility conferred by N348I plus or minus M184V in B and non-B HIV-1 clinical isolates or molecular clones. Data are mean n-fold changes in drug EC₅₀s for mutant viruses compared to those for the wild-type virus across subtypes ± the standard error of the mean from two independent experiments. Statistical analyses using Student's t test compared subtype-specific N348I plus M184V mutant virus with N348I mutant virus. NS, no statistically significant difference. Black bars, N348I; grey bars, N348I plus M184V; white bars, M184V.