Distinct domains of M-T2, the myxoma virus tumor necrosis factor (TNF) receptor homolog, mediate extracellular TNF binding and intracellular apoptosis inhibition

Martha Schreiber, Lisa Sedger, Douglas McFadden

Research output: Contribution to journalArticle

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Abstract

The myxoma virus tumor necrosis factor (TNF) receptor homolog, M-T2, is expressed both as a secreted glycoprotein that inhibits the cytolytic activity of rabbit TNF-α and as an endoglycosidase H-sensitive intracellular species that prevents myxoma virus-infected CD4+ T lymphocytes from undergoing apoptosis. To compare the domains of M-T2 mediating extracellular TNF inhibition and intracellular apoptosis inhibition, recombinant myxoma viruses expressing nested C-terminal truncations of M-T2 protein were constructed. One mutant, ΔL113, containing intact copies of only two cysteine-rich domains, was not secreted and was incapable of binding rabbit TNF-α yet retained full ability to inhibit virus-induced apoptosis of RL-5 cells. Thus, the minimal domain of intracellular M-T2 protein required to inhibit apoptosis is distinct from that required by the extracellular M-T2 for functional TNF-α binding and inhibition. This is the first report of a virus-encoded immunomodolar protein with two distinct antiimmune properties.

Original languageEnglish (US)
Pages (from-to)2171-2181
Number of pages11
JournalJournal of Virology
Volume71
Issue number3
StatePublished - Mar 1 1997
Externally publishedYes

Fingerprint

Myxoma virus
tumor necrosis factors
Tumor Necrosis Factor Receptors
apoptosis
Tumor Necrosis Factor-alpha
Apoptosis
receptors
Rabbits
Viruses
Proteins
rabbits
Glycoside Hydrolases
viruses
proteins
glycosidases
Cysteine
Glycoproteins
cysteine
glycoproteins
T-Lymphocytes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Distinct domains of M-T2, the myxoma virus tumor necrosis factor (TNF) receptor homolog, mediate extracellular TNF binding and intracellular apoptosis inhibition. / Schreiber, Martha; Sedger, Lisa; McFadden, Douglas.

In: Journal of Virology, Vol. 71, No. 3, 01.03.1997, p. 2171-2181.

Research output: Contribution to journalArticle

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