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Tumor necrosis factor alpha stimulates expression of adenovirus early region 3 proteins: implications for viral persistence.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1992 Dec 15; Vol. 89 (24), pp. 11857-61. - Publication Year :
- 1992
-
Abstract
- Human adenovirus (Ad) can cause persistent infections in humans. Early region 3 (E3) of the virus appears to be implicated in this phenomenon. This transcription unit encodes proteins that interfere in various ways with host cell functions, including (i) cell-surface expression of histocompatibility class I antigens (HLA), (ii) cell-surface expression of the epidermal growth factor receptor (EGF-R), and (iii) the biological activity of tumor necrosis factor alpha (TNF-alpha). We transfected the human cell line 293 with the entire E3 region of Ad2 and investigated the influence of the cytokines TNF-alpha and interferon gamma (IFN-gamma) on cell-surface expression of HLA class I and the EGF-R. Whereas IFN-gamma treatment induced expression of HLA to some extent but not that of the EGF-R, TNF-alpha treatment augmented the reduction of these cell-surface molecules. Subsequent studies on the mechanism of this effect showed a TNF-alpha-dependent upregulation of E3 protein (E3/19K) and mRNA. The significance of this phenomenon was confirmed in infection experiments. A dramatic increase in the amount of E3/19K, even after short induction with low doses of TNF-alpha could be demonstrated. The study provides evidence for an interaction between the immune system and Ad in which the virus takes advantage of an immune mediator to escape immunosurveillance of the host.
- Subjects :
- Adenoviridae Infections genetics
Adenovirus E3 Proteins metabolism
Base Sequence
Cell Membrane metabolism
ErbB Receptors metabolism
HLA Antigens metabolism
HeLa Cells
Humans
In Vitro Techniques
Interferon-gamma pharmacology
Molecular Sequence Data
Oligodeoxyribonucleotides chemistry
RNA, Viral genetics
Transfection
Adenovirus E3 Proteins genetics
Adenoviruses, Human genetics
Gene Expression Regulation, Viral drug effects
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 89
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 1334549
- Full Text :
- https://doi.org/10.1073/pnas.89.24.11857