PLoS Pathogens | |
Alpha-defensin-dependent enhancement of enteric viral infection | |
Mayim E. Wiens1  Sarah S. Wilson1  Youngmee Sul1  Mayumi K. Holly1  Jason G. Smith1  Anshu P. Gounder1  Beth A. Bromme1  | |
[1] Department of Microbiology, University of Washington, Seattle, WA, United States of America | |
关键词: Gastrointestinal tract; Viral transmission; infection; Defensins; Viral replication; Colon; Cell binding; Cell cultures; Luciferase; | |
DOI : 10.1371/journal.ppat.1006446 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
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RO201902014708192ZK.pdf | 2767KB | download |