Tumor necrosis factor alpha increases expression of adenovirus E3 proteins.
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 lytic attack by the host immune system: Several E3 proteins (14.7K, 10.4K and 14.5K) protect infected cells from the lytic activity of tumor necrosis factor alpha (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 cell 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 cytokine 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.
Deryckere
F
F
Spemann Laboratories, Max-Planck-Institute for Immunobiology, Freiburg, Germany.
Ebenau-Jehle
C
C
Wold
W S
WS
Burgert
H G
HG
D017503:Adenovirus E3 Proteins / Q000096:biosynthesis* / Q000187:drug effects*; D000818:Animals; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
D017503:Adenovirus E3 Proteins; D014409:Tumor Necrosis Factor-alpha