Related Experiment Video
Updated: Jun 27, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Mutations at human immunodeficiency virus type 1 reverse transcriptase tryptophan repeat motif attenuate the
Chien-Cheng Chiang1, Shiu-Mei Wang, Ying-Tzu Tseng
1Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan.
Abstract:
HIV-1 virus particle processing is mediated by protease (PR), with enzymatic activation triggered by Gag-Pol/Gag-Pol interaction. We previously reported that truncation mutations at the reverse transcriptase (RT) connection subdomain markedly impair virus particle processing, suggesting an important role for the RT subdomain in PR-mediated virus processing. A highly conserved tryptophan (Trp) repeat motif of the HIV-1 RT connection subdomain is involved in RT dimerization. Our goal in this study was to determine whether mutations at the Trp repeat motif have any effect on PR-mediated virus processing. Our results indicate that even though alanine substitutions at W401 (W401A) or at both W401 and W402 (W401A/W402A) have no major effect on steady-state virus processing, the combined W401A/W402A mutations partially negate and the W401A mutation almost completely negates an efavirenz (EFV)-imposed barrier to virus production. The combination of RT instability and poor enzymatic activity reflects a RT dimerization defect incurred by the mutations. We also found that an artificial p66RT carrying the W401A or W401A/W402A mutations was packaged into virions more efficiently than wild-type p66RT, and that the viral incorporation of p66RT is significantly reduced by EFV, implying a novel effect of EFV on RT-Gag interaction. Our results suggest that the Trp repeat motif may play a role in the Gag-Pol/Gag-Pol interaction that contributes to subsequent PR activation.
More Related Videos
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
11:19Pairwise Growth Competition Assay for Determining the Replication Fitness of Human Immunodeficiency Viruses
Published on: May 4, 2015
Related Concept Videos
Inhibitors of Virion Maturation and Assembly
Viral Mutations
Inhibitors of Viral Protein Synthesis
Inhibitors Of Virion Release
Retrovirus Life Cycles
Antiviral Nucleoside Inhibitors