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T cell inactivation by poxviral B22 family proteins increases viral virulence.

Publication ,  Journal Article
Alzhanova, D; Hammarlund, E; Reed, J; Meermeier, E; Rawlings, S; Ray, CA; Edwards, DM; Bimber, B; Legasse, A; Planer, S; Sprague, J; Gold, MC ...
Published in: PLoS Pathog
May 2014

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.

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Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

May 2014

Volume

10

Issue

5

Start / End Page

e1004123

Location

United States

Related Subject Headings

  • Virology
  • Viral Proteins
  • T-Lymphocytes
  • Poxviridae Infections
  • Poxviridae
  • Mpox (monkeypox)
  • Mice, Inbred BALB C
  • Mice
  • Macaca mulatta
  • Jurkat Cells
 

Citation

APA
Chicago
ICMJE
MLA
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Alzhanova, D., Hammarlund, E., Reed, J., Meermeier, E., Rawlings, S., Ray, C. A., … Früh, K. (2014). T cell inactivation by poxviral B22 family proteins increases viral virulence. PLoS Pathog, 10(5), e1004123. https://doi.org/10.1371/journal.ppat.1004123
Alzhanova, Dina, Erika Hammarlund, Jason Reed, Erin Meermeier, Stephanie Rawlings, Caroline A. Ray, David M. Edwards, et al. “T cell inactivation by poxviral B22 family proteins increases viral virulence.PLoS Pathog 10, no. 5 (May 2014): e1004123. https://doi.org/10.1371/journal.ppat.1004123.
Alzhanova D, Hammarlund E, Reed J, Meermeier E, Rawlings S, Ray CA, et al. T cell inactivation by poxviral B22 family proteins increases viral virulence. PLoS Pathog. 2014 May;10(5):e1004123.
Alzhanova, Dina, et al. “T cell inactivation by poxviral B22 family proteins increases viral virulence.PLoS Pathog, vol. 10, no. 5, May 2014, p. e1004123. Pubmed, doi:10.1371/journal.ppat.1004123.
Alzhanova D, Hammarlund E, Reed J, Meermeier E, Rawlings S, Ray CA, Edwards DM, Bimber B, Legasse A, Planer S, Sprague J, Axthelm MK, Pickup DJ, Lewinsohn DM, Gold MC, Wong SW, Sacha JB, Slifka MK, Früh K. T cell inactivation by poxviral B22 family proteins increases viral virulence. PLoS Pathog. 2014 May;10(5):e1004123.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

May 2014

Volume

10

Issue

5

Start / End Page

e1004123

Location

United States

Related Subject Headings

  • Virology
  • Viral Proteins
  • T-Lymphocytes
  • Poxviridae Infections
  • Poxviridae
  • Mpox (monkeypox)
  • Mice, Inbred BALB C
  • Mice
  • Macaca mulatta
  • Jurkat Cells