Alpha-defensin-dependent enhancement of enteric viral infection.
PLoS Pathog
; 13(6): e1006446, 2017 Jun.
Article
em En
| MEDLINE
| ID: mdl-28622386
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adenoviridae
/
Infecções por Adenoviridae
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Alfa-Defensinas
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Intestino Delgado
Limite:
Animals
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Female
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Humans
/
Male
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos