T Cell Inactivation by Poxviral B22 Family Proteins Increases Viral Virulence

Dina Alzhanova, Erika Hammarlund, Jason Reed, Erin Meermeier, Stephanie Rawlings, Caroline A. Ray, David M. Edwards, Ben Bimber, Alfred Legasse, Shannon Planer, Jerald Sprague, Michael K. Axthelm, David J. Pickup, David M. Lewinsohn, Marielle C. Gold, Scott W. Wong, Jonah B. Sacha, Mark K. Slifka, Klaus Früh

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14 Scopus citations

Abstract

Infections with monkeypox, cowpox and weaponized variola virus remain a threat to the increasingly unvaccinated human population, but little is known about their mechanisms of virulence and immune evasion. We now demonstrate that B22 proteins, encoded by the largest genes of these viruses, render human T cells unresponsive to stimulation of the T cell receptor by MHC-dependent antigen presentation or by MHC-independent stimulation. In contrast, stimuli that bypass TCR-signaling are not inhibited. In a non-human primate model of monkeypox, virus lacking the B22R homologue (MPXVΔ197) caused only mild disease with lower viremia and cutaneous pox lesions compared to wild type MPXV which caused high viremia, morbidity and mortality. Since MPXVΔ197-infected animals displayed accelerated T cell responses and less T cell dysregulation than MPXV US2003, we conclude that B22 family proteins cause viral virulence by suppressing T cell control of viral dissemination.

Original languageEnglish (US)
Article numbere1004123
JournalPLoS pathogens
Volume10
Issue number5
DOIs
StatePublished - May 2014

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Alzhanova, D., Hammarlund, E., Reed, J., Meermeier, E., Rawlings, S., Ray, C. A., Edwards, D. M., Bimber, B., Legasse, A., Planer, S., Sprague, J., Axthelm, M. K., Pickup, D. J., Lewinsohn, D. M., Gold, M. C., Wong, S. W., Sacha, J. B., Slifka, M. K., & Früh, K. (2014). T Cell Inactivation by Poxviral B22 Family Proteins Increases Viral Virulence. PLoS pathogens, 10(5), [e1004123]. https://doi.org/10.1371/journal.ppat.1004123