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Journal of General Virology header logo Journal of General Virology

Volume 81, Issue 5

Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins No Access

Abstract

Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the activation of natural killer and T helper 1 cell responses principally by inducing interferon-γ (IFN-γ). Human and mouse secreted IL-18-binding proteins (IL-18BPs) have recently been described which block IL-18 activity but have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus protein was found to block NF-κB activation and induction of IFN-γ in response to IL-18. The highly attenuated vaccinia virus modified virus Ankara encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve further the safety and immunogenicity of this promising human vaccine candidate. We confirm that molluscum contagiosum virus, a molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L). This protein may contribute to the lack of inflammatory response characteristic of molluscum contagiosum virus lesions. The expression of vIL-18BPs by distinct poxvirus genera that cause local or general viral dissemination, or persistent or acute infections in the host, emphasizes the importance of IL-18 in response to viral infections.

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/content/journal/jgv/10.1099/0022-1317-81-5-1223
2000-05-01
2026-03-13

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/content/journal/jgv/10.1099/0022-1317-81-5-1223
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Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins
J. Gen. Virol. 81, 1223 (2000); https://doi.org/10.1099/0022-1317-81-5-1223
/content/journal/jgv/10.1099/0022-1317-81-5-1223
/content/journal/jgv/10.1099/0022-1317-81-5-1223
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