Merrill J E, Koyanagi Y, Chen I S
Department of Neurology, Jonsson Comprehensive Cancer Center, Los Angeles, California.
J Virol. 1989 Oct;63(10):4404-8. doi: 10.1128/JVI.63.10.4404-4408.1989.
Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are important in normal immune processes. In this study, we demonstrate that human immunodeficiency virus type 1 (HIV-1) virions induce normal peripheral blood mononuclear phagocytes to produce both IL-1 and TNF within a few hours after their exposure to virus. The induction of these cytokines by HIV-1 does not require a productive infection. Blocking studies with soluble CD4 indicate that the effect is mediated through the CD4 molecule. In addition, the treatment of mononuclear phagocytes with OKT4A monoclonal antibody mimics the effects of HIV-1. Thus, these results indicate that induction of IL-1 and TNF alpha can occur via signals mediated through the CD4 molecule on mononuclear phagocytes. TNF has been shown by other investigators to induce HIV-1 expression. Therefore, TNF alpha may play a role in autocrine and paracrine regulation of HIV-1 expression. In addition, the induction of IL-1 and TNF by HIV-1 may also contribute to some of the neurologic and physiologic disorders associated with acquired immunodeficiency syndrome.
细胞因子如白细胞介素-1（IL-1）和肿瘤坏死因子α（TNFα）在正常免疫过程中很重要。在本研究中，我们证明1型人类免疫缺陷病毒（HIV-1）病毒粒子在暴露于病毒后的数小时内可诱导正常外周血单核吞噬细胞产生IL-1和TNF。HIV-1对这些细胞因子的诱导不需要有生产性感染。用可溶性CD4进行的阻断研究表明，这种效应是通过CD4分子介导的。此外，用OKT4A单克隆抗体处理单核吞噬细胞可模拟HIV-1的作用。因此，这些结果表明，IL-1和TNFα的诱导可通过单核吞噬细胞上CD4分子介导的信号发生。其他研究人员已表明TNF可诱导HIV-1表达。因此，TNFα可能在HIV-1表达的自分泌和旁分泌调节中起作用。此外，HIV-1对IL-1和TNF的诱导也可能导致一些与获得性免疫缺陷综合征相关的神经和生理紊乱。
