Haffar O K, Moran P A, Smithgall M D, Diegel M L, Sridhar P, Ledbetter J A, Zarling J M, Hu S L
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
J Virol. 1992 Jul;66(7):4279-87. doi: 10.1128/JVI.66.7.4279-4287.1992.
We have previously reported on the assembly of recombinant human immunodeficiency virus (HIV)-like particles that contain gag structural proteins and present env glycoproteins gp120 and gp41 on their surfaces (O. Haffar,. J. Garriques, B. Travis, P. Moran, J. Zarling, and S.-L. Hu, J. Virol. 64:2653-2659, 1990). On the basis of their structures, we hypothesized that the recombinant particles would interfere with virus infection and tested our hypothesis in vitro by using peripheral blood mononuclear cells (PBMC) from HIV type 1-seropositive donors. Addition of the recombinant particles to PBMC concomitant with stimulation by anti-CD3 inhibited virus production, as determined by reduced levels of p24 in the culture supernatants. This inhibition of p24 production correlated with lower levels of cell-associated viral DNA. Several lines of evidence suggested that the recombinant particles exerted their antiviral effects primarily by inhibiting virus production from latently infected cells and not by inhibiting subsequent virus spread. Importantly, CD4+ T-cell stimulation by specific antigen or by anti-CD3 was not inhibited by treatment with the recombinant particles. This apparent selective inhibition of virus replication in infected PBMC represents a novel property of the recombinant HIV-like particles.
我们之前报道过含有gag结构蛋白且表面呈现env糖蛋白gp120和gp41的重组人免疫缺陷病毒（HIV）样颗粒的组装（O. 哈法尔、J. 加里克斯、B. 特拉维斯、P. 莫兰、J. 扎林和胡世亮，《病毒学杂志》64:2653 - 2659，1990年）。基于它们的结构，我们推测重组颗粒会干扰病毒感染，并通过使用来自1型HIV血清阳性供体的外周血单核细胞（PBMC）在体外对我们的推测进行了测试。将重组颗粒添加到PBMC中并同时用抗CD3刺激，如通过培养上清液中p24水平降低所确定的那样，抑制了病毒产生。p24产生的这种抑制与细胞相关病毒DNA水平降低相关。几条证据表明重组颗粒主要通过抑制潜伏感染细胞中的病毒产生而非通过抑制随后的病毒传播来发挥其抗病毒作用。重要的是，用重组颗粒处理并未抑制特异性抗原或抗CD3对CD4 + T细胞的刺激。这种在感染的PBMC中对病毒复制的明显选择性抑制代表了重组HIV样颗粒的一种新特性。
