| First Author | Wilson SS | Year | 2017 |
| Journal | PLoS Pathog | Volume | 13 |
| Issue | 6 | Pages | e1006446 |
| PubMed ID | 28622386 | Mgi Jnum | J:248343 |
| Mgi Id | MGI:5918928 | Doi | 10.1371/journal.ppat.1006446 |
| Citation | Wilson SS, et al. (2017) Alpha-defensin-dependent enhancement of enteric viral infection. PLoS Pathog 13(6):e1006446 |
| abstractText | The small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric alpha-defensins. Although they most commonly function as potent antivirals in cell culture, enteric alpha-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 alpha-defensins on infection by the enteric mouse pathogen, mouse adenovirus 2 (MAdV-2). MAdV-2 infection was increased when enteroids were inoculated across an alpha-defensin gradient in a manner that mimics oral infection but not when alpha-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 alpha-defensins. Thus, our studies have shown that viral infection enhanced by enteric alpha-defensins may reflect the evolution of some viruses to utilize these host proteins to promote their own infection. |
