Pathogenesis of Intestinal and Systemic Rotavirus Infection

Abstract

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 A vaccine was developed and approved, but recommendation for its use was withdrawn because of vaccination-associated adverse events (57).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...

Re-thinking the functions of IgA+plasma cells

“…IEC of the small intestine are the primary site of virus replication. 95 It has been shown that IgA is important for clearance of a primary infection and for protection from reinfection in mice. 96 In humans, IgA is a good correlate of protection against Rotavirus infection, but multiple infections can occur during the lifetime of the host.…”

Recognition of Double-Stranded RNA by TLR3 Induces Severe Small Intestinal Injury in Mice

“…The rotavirus is genetically comprised of 11 segments of dsRNA (9). The purified genomic dsRNA from rotavirus or reovirus are recognizable by TLR3 (10,11), suggesting that genomic dsRNA and TLR3 signaling may be involved in viral pathogenesis.…”

A cross-sectional study on rotavirus infection among students of University Kuala Lumpur Royal College of Medicine Perak in Malaysia

“…However, to reduce the RV-associated acute GE (AG) worldwide, RV vaccines are developed and in 2009, WHO recommended to include prophylactic RV vaccination for infants in all national immunization programs. [2] These vaccines proved efficacy against the viruses such as G and P types (G1, G2, G3, G4, G9 and P [4], P [6], P [8]) that are circulating worldwide and leads to approximately 90% of the disease [7] From the previous studies, it was shown that vaccine efficacy in highly income countries is more than that in middle and low income countries. [8] Alt hough there is lesser effects in middle income settings, these vaccines when introduced into national immunization programs has been associated with a significant decrease in AG-related deaths.…”

“…Since the bolus is osmotically active, the colon cannot able to absorb required water and therefore results in diarrhea. [4] RV diarrhea also causes enterocyte destruction and villus ischemia. Immunity develops with each infection, meaning, subsequent infection is less severe.…”