title: Mutations in the HIV-1 reverse transcriptase tryptophan repeat motif affect virion maturation and Gag-Pol packaging.
abstract: Our goal was to determine the contribution of HIV-1 reverse transcriptase tryptophan repeat motif residues to virion maturation. With the exception of W402A, we found none of the single substitution mutations exerted major impacts on virus assembly or processing. However, all mutants except for W410A exhibited significant decreases in virus-associated RT, presumably a result of unstable RT mutant degradation. Mutations W398A, W401A and W406A decreased the enhancement effect of efavirenz on PR-mediated Gag processing efficiency, which is in agreement with their destabilizing RT effects. Furthermore, combined double or triple W398, W401 and W406 mutations significantly affected virus processing and Gag-Pol packaging. Further analyses suggest that inefficient PR-mediated Gag cleavage partly accounts for the virion processing defect. Our results support the idea that in addition to playing a role in RT heterodimer stabilization, the RT Trp repeat motif in the Gag-Pol context is also involved in PR activation via Gag-Pol/Gag-Pol interaction.
authors: Department of Medical Research and Education, Taipei Veterans General Hospital and Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors: Chien-Cheng
authors: CC
authors: Chiang
authors: Ying-Tzu
authors: YT
authors: Tseng
authors: Kuo-Jung
authors: KJ
authors: Huang
authors: Yen-Yu
authors: YY
authors: Pan
authors: Chin-Tien
authors: CT
authors: Wang
mesh_terms: D019943:Amino Acid Substitution; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D057809:HEK293 Cells; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D020449:Repetitive Sequences, Amino Acid; D014364:Tryptophan / Q000737:chemistry*; D014771:Virion / Q000502:physiology
chemical_list: D015685:Fusion Proteins, gag-pol; D014364:Tryptophan; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase