Tollefson A E, Hermiston T W, Lichtenstein D L, Colle C F, Tripp R A, Dimitrov T, Toth K, Wells C E, Doherty P C, Wold W S
Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, Missouri 63104-1004, USA.
Nature. 1998 Apr 16;392(6677):726-30. doi: 10.1038/33712.
DNA viruses have evolved elaborate mechanisms to overcome host antiviral defences. In adenovirus-infected cells, programmed cell death (apoptosis) induced by the cytokine tumour necrosis factor (TNF) is inhibited by several adenovirus-encoded proteins. Occupation of the cell-surface receptor Fas, a member of the TNF-receptor superfamily that is expressed on most cell types, triggers apoptosis of that cell. Here we show that the adenovirus RID (for receptor internalization and degradation) protein complex, which is an inhibitor of TNF-induced apoptosis, mediates internalization of cell-surface Fas and its destruction inside lysosomes within the cell. Fas has not previously been shown to be internalized and then degraded. RID also mediates internalization of the receptor for epidermal growth factor, but it does not affect the transferrin receptor or class I antigens of the major histocompatibility complex. Removal of Fas from the surface of adenovirus-infected cells expressing RID may allow infected cells to resist Fas-mediated cell death and thus promote their survival.
DNA病毒已经进化出复杂的机制来克服宿主的抗病毒防御。在腺病毒感染的细胞中，细胞因子肿瘤坏死因子（TNF）诱导的程序性细胞死亡（凋亡）被几种腺病毒编码的蛋白质所抑制。细胞表面受体Fas属于TNF受体超家族成员，大多数细胞类型都有表达，占据该受体可触发细胞凋亡。我们在此表明，作为TNF诱导凋亡抑制剂的腺病毒RID（受体内化和降解）蛋白复合物介导细胞表面Fas的内化及其在细胞内溶酶体中的降解。此前尚未发现Fas会被内化然后降解。RID还介导表皮生长因子受体的内化，但不影响转铁蛋白受体或主要组织相容性复合体的I类抗原。从表达RID的腺病毒感染细胞表面去除Fas可能使受感染细胞抵抗Fas介导的细胞死亡，从而促进其存活。
