Yaba monkey tumor virus encodes a functional inhibitor of interleukin-18

Steven H. Nazarian, Masmudur Rahman, Steven J. Werden, Danielle Villeneuve, Xiangzhi Meng, Craig Brunetti, Chalice Valeriano, Christina Wong, Rajkumari Singh, John W. Barrett, Yan Xiang, Douglas McFadden

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)522-528
Number of pages7
JournalJournal of Virology
Volume82
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Yaba monkey tumor virus
interleukin-18
Interleukin-18
Aptitude
Variola virus
Orthopoxvirus
binding proteins
Cytokines
Poxviridae
Surface Plasmon Resonance
Baculoviridae
Virulence Factors
Interferon-gamma
cytokines
human interleukin 18 protein
surface plasmon resonance

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Yaba monkey tumor virus encodes a functional inhibitor of interleukin-18. / Nazarian, Steven H.; Rahman, Masmudur; Werden, Steven J.; Villeneuve, Danielle; Meng, Xiangzhi; Brunetti, Craig; Valeriano, Chalice; Wong, Christina; Singh, Rajkumari; Barrett, John W.; Xiang, Yan; McFadden, Douglas.

In: Journal of Virology, Vol. 82, No. 1, 01.01.2008, p. 522-528.

Research output: Contribution to journalArticle

Nazarian, SH, Rahman, M, Werden, SJ, Villeneuve, D, Meng, X, Brunetti, C, Valeriano, C, Wong, C, Singh, R, Barrett, JW, Xiang, Y & McFadden, D 2008, 'Yaba monkey tumor virus encodes a functional inhibitor of interleukin-18', Journal of Virology, vol. 82, no. 1, pp. 522-528. https://doi.org/10.1128/JVI.00688-07
Nazarian SH, Rahman M, Werden SJ, Villeneuve D, Meng X, Brunetti C et al. Yaba monkey tumor virus encodes a functional inhibitor of interleukin-18. Journal of Virology. 2008 Jan 1;82(1):522-528. https://doi.org/10.1128/JVI.00688-07
Nazarian, Steven H. ; Rahman, Masmudur ; Werden, Steven J. ; Villeneuve, Danielle ; Meng, Xiangzhi ; Brunetti, Craig ; Valeriano, Chalice ; Wong, Christina ; Singh, Rajkumari ; Barrett, John W. ; Xiang, Yan ; McFadden, Douglas. / Yaba monkey tumor virus encodes a functional inhibitor of interleukin-18. In: Journal of Virology. 2008 ; Vol. 82, No. 1. pp. 522-528.
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