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Mathematical analysis demonstrates that interferons-?? and -?? Interact in a multiplicative manner to disrupt herpes simplex virus replication

Journal of Theoretical Biology

By:
, ,
DOI: 10.1016/j.jtbi.2004.12.007

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Abstract

Several studies suggest that the innate interferons (IFNs), IFN-?? and IFN-??, can act in concert with IFN-?? 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-??/?? and IFN-?? 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-?? or IFN-?? on HSV-1 replication over a 320,000-fold range of IFN concentration. Second, pharmacological methods prove that IFN-?? and IFN-?? interact in a greater-than-additive manner to inhibit HSV-1 replication. Finally, the potency with which combinations of IFN-?? and IFN-?? inhibit HSV-1 replication is accurately predicted by multiplying the individual inhibitory effects of each cytokine. Thus, IFN-?? and IFN-?? interact in a multiplicative manner. We infer that a primary antiviral function of IFN-?? lies in its capacity to multiply the potency with which IFN-??/?? restricts HSV-1 replication in vivo. This hypothesis has important ramifications for understanding how T lymphocyte-secreted cytokines such as IFN-?? 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. ?? 2005 Elsevier Ltd. All rights reserved.

Additional Publication Details

Publication type:
Article
Publication Subtype:
Journal Article
Title:
Mathematical analysis demonstrates that interferons-?? and -?? Interact in a multiplicative manner to disrupt herpes simplex virus replication
Series title:
Journal of Theoretical Biology
DOI:
10.1016/j.jtbi.2004.12.007
Volume
234
Issue:
3
Year Published:
2005
Language:
English
Larger Work Type:
Article
Larger Work Subtype:
Journal Article
First page:
439
Last page:
454
Number of Pages:
16