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PMID: 1334549 Published · ppublish English Journal Article

Tumor necrosis factor alpha stimulates expression of adenovirus early region 3 proteins: implications for viral persistence.

Körner H, Fritzsche U, Burgert HG

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.

MeSH Terms
Adenoviridae Infections/genetics Adenovirus E3 Proteins/genetics,metabolism Adenoviruses, Human/genetics Base Sequence Cell Membrane/metabolism ErbB Receptors/metabolism Gene Expression Regulation, Viral/drug effects HLA Antigens/metabolism HeLa Cells Humans In Vitro Techniques Interferon-gamma/pharmacology Molecular Sequence Data Oligodeoxyribonucleotides/chemistry RNA, Viral/genetics Transfection Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Adenovirus E3 Proteins HLA Antigens Oligodeoxyribonucleotides RNA, Viral Tumor Necrosis Factor-alpha Interferon-gamma ErbB Receptors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Körner H
Max-Planck-Institut für Immunobiologie, Spemann Laboratories, Freiburg, Germany.
Fritzsche U
Burgert H G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1992-12-15
Pages
11857-61
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50656
Subset
IM
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