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Updated: Aug 18, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
IL-18 binding and inhibition of interferon gamma induction by human poxvirus-encoded proteins
1Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0445, USA.
Abstract:
Molluscum contagiosum virus (MCV) is a common, human poxvirus that causes small papular skin lesions that persist for long periods without signs of inflammation. Previous studies revealed that MCV encodes a family of proteins with homology to mammalian IL-18 binding proteins. IL-18 is a proinflammatory cytokine that induces synthesis of interferon gamma, activates NK cells, and is required for a T-lymphocyte helper type 1 response. We expressed and purified the proteins encoded by the MC53L and MC54L genes of MCV, as well as their human and murine homologs. All four recombinant proteins were able to bind with high affinity to human and murine IL-18 molecules and inhibited IL-18 mediated interferon gamma production in a dose-dependent manner. The pirating of IL-18 binding proteins by poxviruses and their use as decoy receptors is consistent with the critical role of IL-18 in defense against virus infections and provides a mechanism for evasion of the immune system by MCV.
Insights
Molluscum contagiosum virus (MCV) uses proteins to block interleukin-18 (IL-18), a key immune signal. This viral strategy helps MCV evade the host immune system, allowing skin lesions to persist.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Molluscum contagiosum virus (MCV) causes persistent skin lesions.
- MCV encodes proteins similar to mammalian IL-18 binding proteins.
- Interleukin-18 (IL-18) is crucial for immune responses against viruses.
Purpose of the Study:
- To investigate the interaction between MCV proteins and IL-18.
- To determine if MCV proteins can inhibit IL-18 function.
Main Methods:
- Expressed and purified MCV proteins (MC53L, MC54L) and their human/murine homologs.
- Tested the binding affinity of these proteins to human and murine IL-18.
- Assessed the inhibition of IL-18-mediated interferon-gamma production.
Main Results:
- All four recombinant proteins bound strongly to IL-18.
- MCV proteins effectively inhibited IL-18-induced interferon-gamma production in a dose-dependent manner.
- This suggests poxviruses use IL-18 binding proteins as decoy receptors.
Conclusions:
- MCV proteins act as decoy receptors for IL-18.
- This mechanism allows MCV to evade the host immune system.
- Understanding this interaction is key to combating MCV infections.
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