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Alpha-defensin-dependent enhancement of enteric viral infection.


ABSTRACT: The small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric ?-defensins. Although they most commonly function as potent antivirals in cell culture, enteric ?-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 ?-defensins on infection by the enteric mouse pathogen, mouse adenovirus 2 (MAdV-2). MAdV-2 infection was increased when enteroids were inoculated across an ?-defensin gradient in a manner that mimics oral infection but not when ?-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 ?-defensins. Thus, our studies have shown that viral infection enhanced by enteric ?-defensins may reflect the evolution of some viruses to utilize these host proteins to promote their own infection.

SUBMITTER: Wilson SS 

PROVIDER: S-EPMC5489213 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Alpha-defensin-dependent enhancement of enteric viral infection.

Wilson Sarah S SS   Bromme Beth A BA   Holly Mayumi K MK   Wiens Mayim E ME   Gounder Anshu P AP   Sul Youngmee Y   Smith Jason G JG  

PLoS pathogens 20170616 6


The small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric α-defensins. Although they most commonly function as potent antivirals in cell culture, enteric α-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  ...[more]

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