Display Settings:

Format

Send to:

Choose Destination
PLoS Pathog. 2014 May 15;10(5):e1004123. doi: 10.1371/journal.ppat.1004123. eCollection 2014.

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

Author information

  • 1Vaccine and Gene Therapy Institute, Oregon National Primate Research Center, Portland, Oregon, United States of America.
  • 2Division of Neuroscience, Oregon National Primate Research Center, Portland, Oregon, United States of America.
  • 3Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, United States of America; Portland Veterans Administration Medical Center, Portland, Oregon, United States of America.
  • 4Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
  • 5Division of Pathobiology and Immunology, Oregon National Primate Research Center, Portland, Oregon, United States of America.
  • 6Vaccine and Gene Therapy Institute, Oregon National Primate Research Center, Portland, Oregon, United States of America; Division of Pathobiology and Immunology, Oregon National Primate Research Center, Portland, Oregon, United States of America.

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.

PMID:
24832205
[PubMed - in process]
PMCID:
PMC4022744
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk