Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Virology. 2013 Jul 5;441(2):162-70. doi: 10.1016/j.virol.2013.03.021. Epub 2013 Apr 17.
Numerous in vitro studies attribute to human TRIM5α some modest anti-HIV-1 activity and human population studies suggest some differential effect of TRIM5α polymorphisms on disease progression. If the activity of TRIM5α were relevant in vivo, it could result in positive selection on the viral capsid. To address this issue, we identified 10 positively selected sites in HIV-1 capsid from multiple viral strains and generated 17 clade B viruses carrying a minor (i.e. low frequency) residue or an alanine at those positions. All recombinant viruses were susceptible to the modest effect of common human TRIM5α and allelic variants R136Q, and H419Y; H43Y and G249D TRIM5α were generally inactive. Increased sensitivity to TRIM5α was observed for some capsid variants, suggesting that minor residues are selected against in human populations. On the other hand, the modest potency of human TRIM5α does not translate in escape mutations in the viral capsid.
大量的体外研究表明，人类 TRIM5α 具有一定的抗 HIV-1 活性，而人类群体研究表明，TRIM5α 多态性对疾病进展有一定的影响。如果 TRIM5α 的活性在体内具有相关性，它可能导致病毒衣壳发生阳性选择。为了解决这个问题，我们从多种病毒株中鉴定出 HIV-1 衣壳中的 10 个阳性选择位点，并生成了 17 株带有少数（即低频率）残基或丙氨酸的 B 型 clade 病毒。所有重组病毒都易受常见的人类 TRIM5α 和等位基因变体 R136Q 和 H419Y 的适度影响；H43Y 和 G249D TRIM5α 通常不活跃。一些衣壳变体对 TRIM5α 的敏感性增加，表明在人类群体中，少数残基是被选择的。另一方面，人类 TRIM5α 的适度效力并没有导致病毒衣壳发生逃逸突变。
