Reovirus-induced apoptosis in the intestine limits establishment of enteric infection

Judy J. Brown, Sarah P. Short, Jennifer Stencel-Baerenwald, Kelly Urbanek, Andrea J. Pruijssers, Nicole McAllister, Mine Ikizler, Gwen Taylor, Pavithra Aravamudhan, Solomiia Khomandiak, Bana Jabri, Christopher S. Williams, Terence S. Dermody

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Several viruses induce intestinal epithelial cell death during enteric infection. However, it is unclear whether proapoptotic capacity promotes or inhibits replication in this tissue. We infected mice with two reovirus strains that infect the intestine but differ in the capacity to alter immunological tolerance to new food antigen. Infection with reovirus strain T1L, which induces an inflammatory immune response to fed antigen, is prolonged in the intestine, whereas T3D-RV, which does not induce this response, is rapidly cleared from the intestine. Compared with T1L, T3D-RV infection triggered apoptosis of intestinal epithelial cells and subsequent sloughing of dead cells into the intestinal lumen. We conclude that the infection advantage of T1L derives from its capacity to subvert host restriction by epithelial cell apoptosis, providing a possible mechanism by which T1L enhances inflammatory signals during antigen feeding. Using a panel of T1L × T3D-RV reassortant viruses, we identified the viral M1 and M2 gene segments as determinants of reovirusinduced apoptosis in the intestine. Expression of the T1L M1 and M2 genes in a T3D-RV background was sufficient to limit epithelial cell apoptosis and enhance viral infection to levels displayed by T1L. These findings define additional reovirus gene segments required for enteric infection of mice and illuminate the antiviral effect of intestinal epithelial cell apoptosis in limiting enteric viral infection. Viral strainspecific differences in the capacity to infect the intestine may be useful in identifying viruses capable of ameliorating tolerance to fed antigen in autoimmune conditions like celiac disease.

Original languageEnglish
Article numbere002062-17
JournalJournal of Virology
Volume92
Issue number10
DOIs
StatePublished - 1 May 2018
Externally publishedYes

Keywords

  • Apoptosis
  • Cell death
  • Enteroid
  • Gastrointestinal infection
  • Mucosal immunity
  • Reovirus

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