I, 2. Physiology and pathophysiology of the gut in relation to viral diarrhea

Michelangeli, Fabián A.; Ruiz, Marie Christine

doi:10.1016/s0168-7069(03)09003-7

Cited by 14 publications

(19 citation statements)

References 113 publications

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“…Quantitative PCR revealed that 100-fold more viral RNA was produced in the ileum than in the jejunum or duodenum. This observation was supported by immunohistochemistry showing that more villous cells in the ileum were infected than in the jejunum or the duodenum, an observation also supported by other studies of mice (4,21). Thus, the ileum appears to be the intestinal segment most susceptible to rotavirus infection, regardless of whether the infection takes place in infant or adult mice.…”

Section: Discussionsupporting

confidence: 74%

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

Kordasti

Istrate

Banasaz

et al. 2006

J Virol

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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...

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Section: Discussionsupporting

confidence: 74%

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

Kordasti

Istrate

Banasaz

et al. 2006

J Virol

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“…Infection leads to an increase in [Na ϩ ] i and a decrease in [K ϩ ] i , which appear to be related to increased plasma membrane permeability and not inhibition of the Na ϩ /K ϩ pump (17). Changes in intracellular levels of Na ϩ and K ϩ could impair electroneutral NaCl absorption and Na ϩ -linked nutrient absorption, resulting in a loss of fluid (50). [Na ϩ ] i dysregulation may be related to a general inhibition of the Na ϩ -solute cotransport systems (30).…”

Section: The Molecular Basis Of Diarrhea Inductionmentioning

confidence: 99%

“…In some diarrheal infections, intestinal motility is significantly increased. The intestinal transit time is decreased in rotavirus infection, implying increased motility (50). The ENS generally controls motility, but the molecular stimulator of motility is not known.…”

Section: The Molecular Basis Of Diarrhea Inductionmentioning

confidence: 99%

Pathogenesis of Intestinal and Systemic Rotavirus Infection

Ramig

2004

J Virol

314

230

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Rotaviruses are responsible for significant gastrointestinal disease, primarily in children Ͻ5 years of age and the young of other mammalian species. Each year rotaviruses cause approximately 111 million episodes of gastroenteritis in children, which result in 25 million visits to clinics, 2 million hospitalizations, and 352,000 to 592,000 deaths. On a worldwide basis, nearly every child experiences rotavirus gastroenteritis by age 5, 1 in 5 visits a clinic, 1 in 65 is hospitalized, and 1 in 293 dies. Children in the poorest countries account for 82% of rotavirus deaths (60). This disease burden underscores a need for interventions such as vaccines. A vaccine was developed and approved, but recommendation for its use was withdrawn because of vaccination-associated adverse events (57). Additional information about the molecular biology, immunology, and pathogenesis of rotavirus infection will inform ongoing vaccine development efforts.Our understanding of rotavirus-induced diarrheal disease is incomplete compared to that of several other pathogens (e.g., cholera). Rotavirus diarrhea has been attributed to several different mechanisms, including malabsorption secondary to enterocyte destruction, a virus-encoded toxin, stimulation of the enteric nervous system (ENS), and villus ischemia (13,45). Over the past several years, numerous studies have addressed mechanisms of diarrhea induction at the cellular and tissue levels, and a new understanding of the mechanisms is beginning to emerge. Here I will briefly outline the new data and present our current understanding of how rotaviruses induce diarrhea in the infected host.Recent studies confirm sporadic case reports that rotavirus infection is not confined to the intestine as was generally assumed. Although systemic sequellae to rotavirus infection are apparently rare, reports have continually appeared in the literature, and recent work with animal models has begun to shed light on how the virus spreads to extraintestinal sites. Our current understanding of extraintestinal spread and infection will also be considered below. GENERAL CHARACTERISTICS OF ROTAVIRUS INFECTION AND DISEASE IN HUMANS AND ANIMALSRotavirus. Rotaviruses comprise a genus within the family Reoviridae. The rotavirion has a nonenveloped, complex, triple-layered capsid structure that surrounds a genome composed of 11 segments of double-stranded RNA. There are six structural proteins and six nonstructural proteins, each encoded in a unique genome segment except for nonstructural proteins 5 and 6 (NSP5 and NSP6), which are encoded in overlapping reading frames of a single segment. The rotavirus genus is divided into serological groups (A to E). Groups A to C infect humans, and all groups infect animals. All the information presented here is in regard to group A virus infections.Pathophysiology of rotavirus diarrhea. The enterocytes lining the small intestine are generally divided into two types: enterocytes and crypt cells (Fig. 1). Villus enterocytes are mature, nonproliferating cells covering the vill...

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“…Rotaviruses infect enterocytes of the middle and upper epithelium of the small intestine in vivo, inducing cell death and perturbation of ionic homeostasis. The generation of rotavirus diarrhea is a multifactorial process involving Ca 2ϩ -dependent secretory processes of mediators, water, and electrolytes, as well as the induction of cell death in the different cell types that compose the intestinal epithelium (27,36). The discovery of the functioning of the nonstructural viral protein NSP4 as a viral enterotoxin and of the possible participation of the enteric nervous system in the pathogenesis of diarrhea represents a significant advance in its understanding (3,24,30,31).…”

Section: Rotavirus Infection Modifies Camentioning

confidence: 99%

Expression of Nonstructural Rotavirus Protein NSP4 Mimics Ca ²⁺ Homeostasis Changes Induced by Rotavirus Infection in Cultured Cells

Díaz¹,

Chemello²,

Peña³

et al. 2008

J Virol

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I, 2. Physiology and pathophysiology of the gut in relation to viral diarrhea

Cited by 14 publications

References 113 publications

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

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

Pathogenesis of Intestinal and Systemic Rotavirus Infection

Expression of Nonstructural Rotavirus Protein NSP4 Mimics Ca ²⁺ Homeostasis Changes Induced by Rotavirus Infection in Cultured Cells

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I, 2. Physiology and pathophysiology of the gut in relation to viral diarrhea

Cited by 14 publications

References 113 publications

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

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

Pathogenesis of Intestinal and Systemic Rotavirus Infection

Expression of Nonstructural Rotavirus Protein NSP4 Mimics Ca 2+ Homeostasis Changes Induced by Rotavirus Infection in Cultured Cells

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Expression of Nonstructural Rotavirus Protein NSP4 Mimics Ca ²⁺ Homeostasis Changes Induced by Rotavirus Infection in Cultured Cells