Novel mutations L228I and Y232H cause nonnucleoside reverse transcriptase inhibitor resistance in combinational pattern

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Xiao-Min Zhang
  • Qiwei Zhang
  • Hao Wu
  • Xuan Liu
  • Hin Chu
  • Ke Zhang
  • Jie Zhou
  • Zhi-Wei Chen
  • Dong-Yan Jin
  • Bo-Jian Zheng

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)909-917
Journal / PublicationAIDS Research and Human Retroviruses
Volume32
Issue number9
Online published1 Sept 2016
Publication statusPublished - Sept 2016

Abstract

The emergence of drug resistance mutations is increasing after the implementation of highly active antiretroviral therapy. To characterize two novel mutations L228I and Y232H in the primer grip of reverse transcriptase (RT) of HIV-1 circulating recombination form 08-BC (CRF08-BC) subtype, both mutant clones were constructed to determine their impacts on viral phenotypic susceptibility and replication capacity (RC). Results showed that the novel mutation, L228I, conferred a low-level resistance to etravirine by itself. L228I in combination with Y188C displayed a high level of cross-resistance to both nevirapine (NVP) and efavirenz (EFV). The copresence of A139V and Y232H induced a moderate level of resistance to NVP and EFV. Mutations Y188C/L228I, A139V, Y232H, and A139V/Y232H reduced more than 55% of viral RC compared with that of the wild-type (WT) reference virus. Modeling study suggested that the copresence of Y188C/L228I or A139V/Y232H might induce conformational changes to RT, which might result in reduced drug susceptibility and viral RC due to abolished hydrogen bonding or complex interaction with vicinal residues. Our results demonstrated that L228I and Y232H were novel accessory nonnucleoside reverse transcriptase inhibitor resistance-related mutations and provided valuable information for clinicians to design more effective treatment to patients infected with HIV-1 subtype CRF08-BC.

Citation Format(s)

Novel mutations L228I and Y232H cause nonnucleoside reverse transcriptase inhibitor resistance in combinational pattern. / Zhang, Xiao-Min; Zhang, Qiwei; Wu, Hao et al.
In: AIDS Research and Human Retroviruses, Vol. 32, No. 9, 09.2016, p. 909-917.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review