Adenovirus Infection Dramatically Augments Lipopolysaccharide-Induced TNF Production and Sensitizes to Lethal Shock

We observed a remarkable synergism of adenoviruses and LPS in triggering the production of TNF in intact animals. We found that in mice pre-exposed to adenoviruses, LPS injections generated extremely high levels of TNF with altered kinetics. The elevated TNF synthesis stemmed mostly from posttranscr...

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 175; no. 3; pp. 1498 - 1506
Main Authors:	Fejer, Gyorgy, Szalay, Katalin, Gyory, Ildiko, Fejes, Maria, Kusz, Erzsebet, Nedieanu, Saviana, Pali, Tibor, Schmidt, Tibor, Siklodi, Botond, Lazar, Gyorgy, Jr, Lazar, Gyorgy, Sr, Duda, Erno
Format:	Journal Article
Language:	English
Published:	United States Am Assoc Immnol 01-08-2005
Subjects:	Adenoviridae Infections - blood Adenoviridae Infections - immunology Adenoviridae Infections - metabolism Animals Capsid - metabolism Cell Line Cells, Cultured Cytokines - biosynthesis Cytokines - genetics Dose-Response Relationship, Immunologic Gene Expression Regulation, Viral - immunology Humans Injections, Intraperitoneal Lipopolysaccharides - administration & dosage Lipopolysaccharides - toxicity Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Nude Nitric Oxide - biosynthesis Organ Specificity - immunology Serotyping Shock, Septic - immunology Shock, Septic - mortality Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - metabolism Up-Regulation - genetics Up-Regulation - immunology Virion - immunology Virus Activation - immunology
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Summary:	We observed a remarkable synergism of adenoviruses and LPS in triggering the production of TNF in intact animals. We found that in mice pre-exposed to adenoviruses, LPS injections generated extremely high levels of TNF with altered kinetics. The elevated TNF synthesis stemmed mostly from posttranscriptional up-regulation of TNF production, although transcription of the TNF gene was also induced. Adenoviruses and LPS exhibited a significant but less dramatic synergism in the induction of IL-6, IFN-gamma, and NO. Only marginal changes were detected in the synthesis of a panel of other cytokines. Different serotypes of the virus showed practically identical effects. As deletion mutants lacking indispensable viral genes or UV inactivated virions exhibited similar activities as the infectious, wild-type virus, it seems unlikely that the viral genome plays any significant role in the phenomenon. Published data indicate that other viruses also show some kind of synergism with LPS, although by different cellular mechanisms. T cells and their IFN-gamma production--crucial in the synergism of influenza viruses and LPS--were dispensable in our experiments. We suggest that the phenomenon is probably a general one: an overlap between different molecular mechanisms detecting bacterial and viral pathogens and inducing mediators of nonspecific cell-mediated host defense. The synergism of viruses and LPS (bacteria) could be a concern in medical practice as well as in gene therapy experiments with high doses of recombinant adenoviruses.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.175.3.1498