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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • May 2014

Published In

Volume / Issue

  • 10 / 5

Start / End Page

  • e1004123 -

PubMed ID

  • 24832205

Pubmed Central ID

  • 24832205

Electronic International Standard Serial Number (EISSN)

  • 1553-7374

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1004123

Language

  • eng

Conference Location

  • United States