Related Experiment Video
Updated: Jun 14, 2026
05:46
Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs
Hong-Tao Xu1, Yudong Quan, Susan M Schader
1McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
Antimicrobial Agents and Chemotherapy
|March 24, 2010
Summary
The M230L mutation in HIV-1 reverse transcriptase (RT) causes resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). This mutation also reduces viral replication capacity and enzyme function.
Area of Science:
- Virology
- Molecular Biology
- Drug Resistance
Background:
- The M230L mutation in HIV-1 reverse transcriptase (RT) is linked to resistance against first-generation nonnucleoside reverse transcriptase inhibitors (NNRTIs).
- Understanding the impact of M230L on viral fitness and resistance profiles is crucial for developing effective HIV therapies.
Purpose of the Study:
- To investigate the effects of the M230L mutation on HIV-1 RT enzyme function.
- To assess the impact of M230L on viral replication capacity (RC).
- To determine the resistance profile of M230L against first-generation NNRTIs (efavirenz, nevirapine) and the second-generation NNRTI etravirine.
Main Methods:
- Phenotyping assays using TZM-bl cells to evaluate NNRTI resistance.
- Construction and analysis of recombinant HIV-1 viruses with and without the M230L mutation.
- Purification and biochemical characterization of wild-type (WT) and M230L mutant HIV-1 RT enzymes.
- Assays to measure enzyme activities including minus-strand DNA synthesis, DNA- and RNA-dependent polymerase activities, processivity, and RNase H activity.
Main Results:
- M230L conferred varying degrees of resistance to efavirenz (EFV), nevirapine (NVP), and etravirine (ETR).
- Recombinant viruses with M230L showed an 8-fold reduction in replication capacity compared to WT.
- Purified M230L mutant RT exhibited deficiencies in DNA/RNA synthesis, polymerase activity, processivity, and RNase H activity.
Conclusions:
- The M230L mutation significantly impacts HIV-1 RT function, leading to reduced enzyme activities and impaired viral replication kinetics.
- M230L confers resistance to both first- and second-generation NNRTIs, highlighting its clinical significance in HIV treatment.
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