PMID- 17959666 OWN - NLM STAT- MEDLINE DCOM- 20080110 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 82 IP - 1 DP - 2008 Jan TI - Yaba monkey tumor virus encodes a functional inhibitor of interleukin-18. PG - 522-8 AB - Interleukin-18 (IL-18) is a critical proinflammatory cytokine whose extracellular bioactivity is regulated by a cellular IL-18 binding protein (IL-18BP). Many poxviruses have acquired variants of this IL-18BP gene, some of which have been shown to act as viral virulence factors. Yaba monkey tumor virus (YMTV) encodes a related family member, 14L, which is similar to the orthopoxvirus IL-18BPs. YMTV 14L was expressed from a baculovirus system and tested for its ability to bind and inhibit IL-18. We found that YMTV 14L bound both human IL-18 (hIL-18) and murine IL-18 with high affinity, at 4.1 nM and 6.5 nM, respectively. YMTV 14L was able to fully sequester hIL-18 but could only partially inhibit the biological activity of hIL-18 as measured by gamma interferon secretion from KG-1 cells. Additionally, 17 hIL-18 point mutants were tested by surface plasmon resonance for their ability to bind to YMTV 14L. Two clusters of hIL-18 surface residues were found to be important for the hIL-18-YMTV 14L interaction, in contrast to results for the Variola virus IL-18BP, which has been shown to primarily interact with a single cluster of three amino acids. The altered binding specificity of YMTV 14L most likely represents an adaptation resulting in increased fitness of the virus and affirms the plasticity of poxviral inhibitor domains that target cytokines like IL-18. FAU - Nazarian, Steven H AU - Nazarian SH AD - University of Florida, 1600 SW Archer Road, ARB Room R4-295, P.O. Box 100332, Gainesville, FL 32610, USA. FAU - Rahman, Masmudur M AU - Rahman MM FAU - Werden, Steven J AU - Werden SJ FAU - Villeneuve, Danielle AU - Villeneuve D FAU - Meng, Xiangzhi AU - Meng X FAU - Brunetti, Craig AU - Brunetti C FAU - Valeriano, Chalice AU - Valeriano C FAU - Wong, Christina AU - Wong C FAU - Singh, Rajkumari AU - Singh R FAU - Barrett, John W AU - Barrett JW FAU - Xiang, Yan AU - Xiang Y FAU - McFadden, Grant AU - McFadden G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071024 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Interleukin-18) RN - 0 (Viral Proteins) RN - 0 (interleukin-18 binding protein) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Cell Line MH - Humans MH - Intercellular Signaling Peptides and Proteins/*physiology MH - Interferon-gamma/biosynthesis MH - Interleukin-18/*antagonists & inhibitors MH - Mutagenesis, Site-Directed MH - Point Mutation MH - Protein Binding MH - Protein Interaction Mapping MH - Surface Plasmon Resonance MH - Viral Proteins/*physiology MH - Yaba monkey tumor virus/*immunology PMC - PMC2224402 EDAT- 2007/10/26 09:00 MHDA- 2008/01/11 09:00 PMCR- 2008/05/01 CRDT- 2007/10/26 09:00 PHST- 2007/10/26 09:00 [pubmed] PHST- 2008/01/11 09:00 [medline] PHST- 2007/10/26 09:00 [entrez] PHST- 2008/05/01 00:00 [pmc-release] AID - JVI.00688-07 [pii] AID - 0688-07 [pii] AID - 10.1128/JVI.00688-07 [doi] PST - ppublish SO - J Virol. 2008 Jan;82(1):522-8. doi: 10.1128/JVI.00688-07. Epub 2007 Oct 24.