%0 Journal Article
%T Alpha-defensin-dependent enhancement of enteric viral infection
%A Anshu P. Gounder
%A Beth A. Bromme
%A Jason G. Smith
%A Mayim E. Wiens
%A Mayumi K. Holly
%A Sarah S. Wilson
%A Youngmee Sul
%J -
%D 2017
%R 10.1371/journal.ppat.1006446
%X The small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric ¦Á-defensins. Although they most commonly function as potent antivirals in cell culture, enteric ¦Á-defensins have also been shown to enhance some viral infections in vitro. Efforts to determine the physiologic relevance of enhanced infection have been limited by the absence of a suitable cell culture system. To address this issue, here we use primary stem cell-derived small intestinal enteroids to examine the impact of naturally secreted ¦Á-defensins on infection by the enteric mouse pathogen, mouse adenovirus 2 (MAdV-2). MAdV-2 infection was increased when enteroids were inoculated across an ¦Á-defensin gradient in a manner that mimics oral infection but not when ¦Á-defensin levels were absent or bypassed through other routes of inoculation. This increased infection was a result of receptor-independent binding of virus to the cell surface. The enteroid experiments accurately predicted increased MAdV-2 shedding in the feces of wild type mice compared to mice lacking functional ¦Á-defensins. Thus, our studies have shown that viral infection enhanced by enteric ¦Á-defensins may reflect the evolution of some viruses to utilize these host proteins to promote their own infection
%K Gastrointestinal tract
%K Viral transmission and infection
%K Defensins
%K Viral replication
%K Colon
%K Cell binding
%K Cell cultures
%K Luciferase
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006446