TUMOR-NECROSIS-FACTOR-ALPHA INCREASES EXPRESSION OF ADENOVIRUS E3 PROTEINS

被引：14

作者：

DERYCKERE, F

EBENAUJEHLE, C

WOLD, WSM

BURGERT, HG

机构：

[1] MAX PLANCK INST IMMUNBIOL,HANS SPEMANN LAB,D-79108 FREIBURG,GERMANY

[2] ST LOUIS UNIV,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO

来源：

IMMUNOBIOLOGY | 1995年 / 193卷 / 2-4期

关键词：

D O I：

10.1016/S0171-2985(11)80542-5

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Human adenovirus can cause persistent infections in man. Implicated in this phenomenon is the early transcription unit 3 (E3) of the virus which encodes proteins that are primarily devoted to counteract the lyric attack by the host immune system: Several E3 proteins (14.7K, 10.4K and 14.5K) protect infected cells from the lyric activity of tumor necrosis factor a (TNF) while the most abundant E3 protein, E3/19K, inhibits lysis by cytotoxic T cells. E3/19K interacts with class I histocompatibility (MHC) antigens in the rough endoplasmic reticulum, thereby preventing transport of MHC molecules to the ceil surface and, consequently, MHC-restricted T cell recognition. In addition, the 10.4K and 14.5K proteins downregulate cell surface expression of the epidermal growth factor receptor. Interestingly, adenovirus-mediated pneumonia in mice is accompanied by induction of TNF, a cyrokine known to enhance MHC expression. We previously showed that TNF is unable to restore MHC class I expression in E3/19K: transfected cells but rather leads to a further reduction of MHC antigens. This effect correlated with an increased production of E3/19K mRNA and protein. We now find in addition an upregulation of other E3 proteins in transfected as well as in infected cells. This coordinated upregulation of E3 proteins indicates that TNF stimulates the E3 promoter, probably by activating the transcription factor NF-kappa B. Thus, a novel interaction between the immune system and adenovirus is described in which the virus takes advantage of an immune mediator to promote expression of several immunosubversive proteins supporting its escape from immunosurveillance.

引用

页码：186 / 192

页数：7

共 16 条

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