Official websites use. Share sensitive information only on official, secure websites. Author Contributions: ZZ led performance of all experiments. JZ, ZS helped with specimen analysis. XS and FS provided advice and key reagents. AG helped design study and drafted manuscript. Gewirtz, Ph. This study investigated the mechanism by which these cytokines act to impede RV. IL drove IEC proliferation and migration toward villus tips, which resulted in increased extrusion of highly differentiated IEC that serve as the site of RV replication.
Together, these actions resulted in rapid and complete expulsion of RV, even in hosts with severely compromised immune systems. These results suggest that a cocktail of IL and IL might be a means of treating viral infections that preferentially target short-lived epithelial cells.
RV is a double-stranded RNA virus that primarily infects intestinal epithelial cells IEC that line the villus tips of the ileum, resulting in severe life-threatening diarrhea in young children and moderate gastrointestinal distress in adults 2 — 4. Such tropism and pathogenesis is faithfully recapitulated in RV-infected mice, making the mouse model of RV useful for studying basic aspects of RV immunity and disease pathophysiology. Further, the RV mouse model may prove a useful platform for discovery of novel means to treat and prevent RV infection, especially in scenarios when adaptive immunity, which normally plays an essential role in clearing RV, is not functioning adequately.
However, the mechanisms by which these cytokines impede RV infection remained unknown. We previously reported that systemic administration of bacterial flagellin elicits TLR5-mediated production of IL and NLRC4-mediated generation of IL that can act in concert to prevent or treat rotavirus RV and some other enteric viral infections 5.
In WT mice, a sufficiently high doses of recombinant IL can, by itself, fully prevent RV infection while lower doses of exogenously administered IL and IL dramatically reduced the extent of RV infection, while the combination of these cytokines eliminated evidence of infection Figure 1A.
