Journal Article

Alpha-defensin-dependent enhancement of enteric viral infection

Holly, Mayumi K., Sul, Youngmee, Smith, Jason G., Wiens, Mayim E., Bromme, Beth A., Wilson, Sarah S., Gounder, Anshu P.

2017

Overview

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 enteroids to examine the impact of naturally secreted α-defensins on infection by the enteric mouse pathogen, mouse adenovirus 2 (MAdV-2). MAdV-2 infection was increased when enteroids were inoculated across an α-defensin gradient in a manner that mimics oral infection but not when α-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 α-defensins. Thus, our studies have shown that viral infection enhanced by enteric α-defensins may reflect the evolution of some viruses to utilize these host proteins to promote their own infection.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenoviridae - genetics / Adenoviridae - physiology / Adenoviridae Infections - virology / Adenoviruses / alpha-Defensins - genetics / alpha-Defensins - metabolism / Animals / Antimicrobial peptides / Antiviral agents / Biology and Life Sciences / Cell culture / Cell surface / Defensins / Dendritic cells / Epithelium / Female / Health services / Host-Pathogen Interactions / Humans / In vitro methods and tests / Infections / Infectious diseases / Inoculation / Intestine / Intestine, Small - metabolism / Intestine, Small - virology / Male / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Mice, Knockout / Oral infection / Pathogens / Peptides / Proteins / Public health / Research and Analysis Methods / Shedding / Small intestine / Stem cells / Studies / Viral infections / Virus diseases / Virus Shedding / Viruses