Interaction of human TNF and β2-microglobulin with Tanapox virus-encoded TNF inhibitor, TPV-2L

Masmudur M. Rahman, David Jeng, Rajkumari Singh, Jake Coughlin, Karim Essani, Grant McFadden

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Tanapox virus (TPV) encodes and expresses a secreted TNF-binding protein, TPV-2L or gp38, that displays inhibitory properties against TNF from diverse mammalian species, including human, monkey, canine and rabbit. TPV-2L also has sequence similarity with the MHC-class I heavy chain and interacts differently with human TNF as compared to the known cellular TNF receptors or any of the known virus-encoded TNF receptor homologs derived from many poxviruses. In order to determine the TNF binding region in TPV-2L, various TPV-2L C-terminal truncations and internal deletions were created and the muteins were expressed using recombinant baculovirus vectors. C-terminal deletions from TPV-2L resulted in reduced binding affinity for human TNF and specific mutants of TNF that discriminate between TNF-R1 and TNF-R2. However, deletion of C-terminal 42 amino acid residues totally abolished the binding of human TNF and its mutants. Removal of any of the predicted internal domains resulted in a mutant TPV-2L protein incapable of binding to human TNF. Deletion of C-terminal residues also affected the ability of TPV-2L to block TNF-induced cellular cytotoxicity. In addition to TNF, TPV-2L can also form complexes with human β2-microglobulin to form a novel macromolecular complex. In summary, the TPV-2L protein is a bona fide MHC-1 heavy chain family member that binds and inhibits human TNF in a fashion very distinct from other known poxvirus-encoded TNF inhibitors, and also can form a novel complex with the human MHC-1 light chain, β2-microglobulin.

Original languageEnglish (US)
Pages (from-to)462-468
Number of pages7
JournalVirology
Volume386
Issue number2
DOIs
StatePublished - Apr 10 2009
Externally publishedYes

Keywords

  • MHC-class I
  • Poxvirus
  • Surface Plasmon Resonance
  • Tanapox virus
  • Tumor necrosis factor
  • Tumor necrosis factor receptor
  • Viral TNF inhibitor
  • β2 microglobulin

ASJC Scopus subject areas

  • Virology

Fingerprint Dive into the research topics of 'Interaction of human TNF and β2-microglobulin with Tanapox virus-encoded TNF inhibitor, TPV-2L'. Together they form a unique fingerprint.

  • Cite this