| Mathematical analysis demonstrates that interferons-beta and -gamma interact in a multiplicative manner to disrupt herpes simplex virus replication. | |
| | |
MedLine Citation:
|
PMID: 15784277 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Several studies suggest that the innate interferons (IFNs), IFN-alpha and IFN-beta, can act in concert with IFN-gamma to synergistically inhibit the replication of cytomegalovirus and herpes simplex virus type 1 (HSV-1). The significance of this observation is not yet agreed upon in large part because the nature and magnitude of the interaction between IFN-alpha/beta and IFN-gamma is not well defined. In the current study, we resolve this issue by demonstrating three points. First, the hyperbolic tangent function, tanh (x), can be used to describe the individual effects of IFN-beta or IFN-gamma on HSV-1 replication over a 320,000-fold range of IFN concentration. Second, pharmacological methods prove that IFN-beta and IFN-gamma interact in a greater-than-additive manner to inhibit HSV-1 replication. Finally, the potency with which combinations of IFN-beta and IFN-gamma inhibit HSV-1 replication is accurately predicted by multiplying the individual inhibitory effects of each cytokine. Thus, IFN-beta and IFN-gamma interact in a multiplicative manner. We infer that a primary antiviral function of IFN-gamma lies in its capacity to multiply the potency with which IFN-alpha/beta restricts HSV-1 replication in vivo. This hypothesis has important ramifications for understanding how T lymphocyte-secreted cytokines such as IFN-gamma can force herpesviruses into a latent state without destroying the neurons or leukocytes that continue to harbor these viral infections for the lifetime of the host. |
| | |
Authors:
|
William P Halford; Keith J Halford; Amy T Pierce |
Related Documents
:
|
2477147 - Synergistic cytotoxic effects of recombinant human tumor necrosis factor, interferons, ... 8608597 - Targeted disruption of the stat1 gene in mice reveals unexpected physiologic specificit... 7685917 - Alpha-methyl-p-tyrosine reduces poly i:c-induced augmenting interferon production and s... 22654847 - Neuroregenerative mechanisms of allopregnanolone in alzheimer's disease. 17868957 - Enhancement of immunity to an escherichia coli vaccine in mice orally inoculated with a... 2298497 - Egf and tgf-alpha, the ligands of hyperproduced egfr in human esophageal carcinoma cell... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Date: 2005-01-25 |
Journal Detail:
|
Title: Journal of theoretical biology Volume: 234 ISSN: 0022-5193 ISO Abbreviation: J. Theor. Biol. Publication Date: 2005 Jun |
Date Detail:
|
Created Date: 2005-03-23 Completed Date: 2005-06-09 Revised Date: 2010-04-21 |
Medline Journal Info:
|
Nlm Unique ID: 0376342 Medline TA: J Theor Biol Country: England |
Other Details:
|
Languages: eng Pagination: 439-54 Citation Subset: IM |
Affiliation:
|
Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. halford@montana.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Drug Synergism Herpes Simplex / immunology*, virology Herpesvirus 1, Human / physiology* Interferon-beta / immunology* Interferon-gamma / immunology* Models, Immunological* T-Lymphocytes / immunology Virus Latency Virus Replication / drug effects |
| Grant Support | |
ID/Acronym/Agency:
|
AI 51414/AI/NIAID NIH HHS; R01 AI051414-03/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
|
77238-31-4/Interferon-beta; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Response to temporal parameter fluctuations in biochemical networks.
Next Document: NADPH-dependent metabolism of 17beta-estradiol and estrone to polar and nonpolar metabolites by huma...