Mutations in the Primer Grip of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Impair Proviral DNA Synthesis and Virion Maturation

This report describes the effects of mutating highly conserved residues in the primer grip domain of human immunodeficiency virus type 1 reverse transcriptase (RT) on virus formation and infectivity. Among a series of RT mutant viruses, three (M230A, L234D, and W239A) were found to be noninfectious or very poorly infectious. Our data indicate that these mutations in RT caused severe defects in proviral DNA synthesis. Interestingly, assembly and maturation of mutant virus M230A were similar to those of the wild type, while mutants L234D and W239A showed impaired maturation. The immature morphology of RT mutants L234D and W239A is due at least in part to premature cleavage of the gag-pol precursor, prior to virion budding, indicating that intracellular stability of Pr160(gag-pol) is of key importance during virus assembly.

本报告阐述了人类免疫缺陷病毒1型（human immunodeficiency virus type 1）逆转录酶（reverse transcriptase, RT）引物握持结构域（primer grip domain）内高度保守残基的突变对病毒形成与感染性的影响。在一系列RT突变病毒中，三株突变体（M230A、L234D及W239A）被证实无感染性或感染能力极弱。本研究数据表明，上述RT突变会导致前病毒DNA（proviral DNA）合成出现严重缺陷。值得注意的是，M230A突变病毒的组装与成熟过程与野生型（wild type）病毒基本一致，而L234D和W239A突变体则表现出成熟过程受损。RT突变体L234D与W239A呈现未成熟形态的原因至少部分在于病毒颗粒出芽前gag-pol前体发生了过早切割，这表明Pr160(gag-pol)的细胞内稳定性在病毒组装过程中至关重要。