Rotavirus Infection Is Not Associated with Small Intestinal Fluid Secretion in the Adult Mouse

Abstract

In contrast to humans, adult but not infant small animals are resistant to rotavirus diarrhea. The pathophysiological mechanism behind this age-restricted diarrhea is currently unresolved, and this question was investigated by studying the secretory state of the small intestines of adult mice infected with rotavirus. Immunohistochemistry and histological examinations revealed that rotavirus (strain EDIM) infects all parts of the small intestines of adult mice, with significant numbers of infected cells in the ilea at 2 and 4 days postinfection. Furthermore, quantitative PCR revealed that 100-fold more viral RNA was produced in the ilea than in the jejuna or duodena of adult mice. In vitro perfusion experiments of the small intestine did not reveal any significant changes in net fluid secretion among mice infected for 3 days or 4 days or in those that were noninfected (37 ؎ 9 l · h ؊1 · cm ؊1 , 22 ؎ 13 l · h ؊1 · cm ؊1 , and 33 ؎ 6 l · h ؊1 · cm ؊1 , respectively) or in transmucosal potential difference (4.0 ؎ 0.3 mV versus 3.9 ؎ 0.4 mV), a marker for active chloride secretion, between control and rotavirus-infected mice. In vivo experiments also did not show any differences in potential difference between uninfected and infected small intestines. Furthermore, no significant differences in weight between infected and uninfected small intestines were found, nor were any differences in fecal output observed between infected and control mice. Altogether, these data suggest that rotavirus infection is not sufficient to stimulate chloride and water secretion from the small intestines of adult mice.Rotavirus (RV) is an important cause of acute gastroenteritis in young children and is also an important pathogen in several animal species. In contrast to the situation in humans, where symptomatic reinfections do occur in adults (1,23,30), most adult small animals show an age-dependent resistance to symptomatic RV infections (4,5,12,38). The pathophysiological mechanisms behind this age-dependent resistance are currently unresolved, but it has been proposed that they are due to compensatory fluid absorption by the larger colons of older animals. It has also been suggested that the low expression of proteolytic enzymes in newborn mice is a possible mechanism (13). Furthermore, an interesting observation is that the agedependent resistance in adult mice correlates with the lack of chemokine responses (28). We have previously shown that in infant mice, rotavirus infection gives rise to an increased fluid secretion and an increased transmucosal potential difference (PD), a marker for active chloride secretion (16). The aim of this study was to investigate the secretory state of the small intestines of adult mice. Using established (16,32,33) in vivo and in vitro methods, we measured net fluid transport and PD and found that in spite of virus infection, there was no evidence for chloride or water secretion from the small intestines of murine rotavirus-infected adult mice. This suggests that rotavirus infection in adult mice, in...

Rotavirus Infection Increases Intestinal Motility but Not Permeability at the Onset of Diarrhea

“…2A and B). This conclusion is further supported by our observation that even adult mice have similar pathological lesions at the same time points but no diarrhea (28). Apparently, RV-induced pathological lesions per se in the small intestine (Fig.…”

“…Previous studies have shown that the small intestine of infant mice (11,35) but not adult mice (28) respond with electrolyte and water secretion (diarrhea) following infection with murine RV. In diarrhea-resistant adult mice there was a most modest increase of intestinal motility at 24 h p.i.…”

“…Mice (adults and infants) were orally infected with 10 l/animal (100ϫ the dose causing diarrhea in 50% of animals [DD 50 ]) of wild-type murine RV (EDIM strain) as previously described (28). Only infant mice were examined for diarrhea, since adult mice have previously been shown not to develop diarrhea (29).…”

“…(Fig. 5A and B and Table 3), time points when mice exhibited diarrhea, enterocyte vacuolization (28), and villus atrophy in the jejunum part of the small intestine ( Fig. 2A and B).…”

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

“…The myenteric plexus provides motor innervation to the circular muscle layer and the longitudinal muscle and regulates intestinal motility including peristalsis 142 . Over the years, it has become more and more evident that ENS is involved in rotavirus diarrhea 30,[74][75][76][77] . By blocking enteric neurotransmitters, that can act to induce active secretion (e.g.…”