{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":53,"searchCount":0},"additional":{"submitter":["Wilson SS"],"funding":["National Institute of Allergy and Infectious Diseases","NIAID NIH HHS","University of Washington","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["e1006446"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5489213"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(6)"],"pubmed_abstract":["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."],"journal":["PLoS pathogens"],"pubmed_title":["Alpha-defensin-dependent enhancement of enteric viral infection."],"pmcid":["PMC5489213"],"funding_grant_id":["R01 AI104920","T32 AI083203","Helen Riaboff Whiteley Endowment","T32 GM007270"],"pubmed_authors":["Wiens ME","Holly MK","Wilson SS","Smith JG","Bromme BA","Gounder AP","Sul Y"],"view_count":["53"],"additional_accession":[]},"is_claimable":false,"name":"Alpha-defensin-dependent enhancement of enteric viral infection.","description":"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.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Jun","modification":"2024-10-19T10:30:10.243Z","creation":"2019-03-27T02:48:47Z"},"accession":"S-EPMC5489213","cross_references":{"pubmed":["28622386"],"doi":["10.1371/journal.ppat.1006446"]}}