Ausschuss für Hygiene

Rotaviruses

The genus rotavirus is divided into a number of groups between which antigenicity is distinct (Bridger 1994)

Host species:

  • laboratory animals, particularly mice, rats, and rabbits (Sheridan & Vonderfecht 1986, Vonderfecht 1986, National Research Council 1991, Harkness & Wagner 1995)
  • wide range of domestic and wild mammalian animals, birds, humans

Properties:

  • murine rotavirus is stable at –70oC but unstable at –24, 4, and 37oC; not resistant to environmental conditions (Sheridan & Vonderfecht 1986, National Research Council 1991, Vonderfecht 1994)
  • rotaviruses tend to be stable at low pH and labile at pH values above 10.0

Strain susceptibility:

  • naive BALB/c mice of all ages are susceptible to murine rotavirus; other strains of mice, such as C57BL/6, are much more resistant to infection with murine rotavirus as adults (Ward & McNeal 1999)
  • Prkdcscid mice may become persistently infected with rotavirus (Riepenhoff-Talty et al. 1987, Franco & Greenberg 1999)

Organotropism:

  • fenterotropic
  • hepatobiliarytropic in heterologously infected mice (Uhnoo et al. 1990b, Petersen et al. 1998)

Clinical disease:

  • usually inapparent in adults
  • major cause of acute diarrhea in infants and in the young of other mammalian and avian species
  • the natural disease in mice is caused by group A rotaviruses and has been known as "epizootic diarrhea of infant mice" (EDIM); the susceptibility to EDIM is dependent on the immunological status and the age of the host, and peaks between 3-14 days of age (Sheridan & Vonderfecht 1986, National Research Council 1991, Harkness & Wagner 1995, Ball et al. 1996)
  • the natural disease in rats has been named "infectious diarrhea of infant rats" (IDIR) and is caused by a group B rotavirus; the clinical course of IDIR is similar to that of EDIM (Vonderfecht 1986, National Research Council 1991, Harkness & Wagner 1995)
  • rabbits ranging from 1-12 weeks of age may exhibit clinical signs of diarrhea following infection with group A rotaviruses (Thouless et al.1988, Vonderfecht 1994)

Pathology:

  • histopathologic changes in the intestine are confined to the small intestine and most prominent at the tips of villi; lesions include swelling and vacuolation of epithelial cells, formation of epithelial syncytial cells, intracytoplasmic inclusion bodies in the epithelial cells, epithelial cell necrosis, sloughing of epithelial cells into the intestinal lumen, villus atrophy and blunting, edema and mild inflammation in the lamina propria of villi (Sheridan & Vonderfecht 1986, Vonderfecht 1986, National Research Council 1991, Salim et al. 1995, Ciarlet et al. 1998)
  • hepatitis, cholangitis, and biliary atresia in infant Balb/c mice after experimental infection with rhesus rotavirus (Uhnoo et al. 1990b, Petersen et al. 1998)
  • Morbidity and mortality
  • rotaviruses are highly contagious and infection is easily spread within a group (Kraft 1958)
  • high morbidity (in the young) and low mortality; mortality is more common in infected rabbits (Vonderfecht 1994)

Zoonotic relevance:

  • animal-to-human transmission may occur (Nakagomi et al. 1992, Shirane & Nakagomi 1994) but does not appear to be common

Interference with research:

Physiology

  • rotaviruses bind to the neutral glycosphingolipid gangliotetraosylceramide (Willoughby et al. 1990) and to O-linked sialylglycoconjugates and sialomucins (Willoughby 1993)
  • malnutrition and other dietary alterations may enhance murine rotavirus infection (Morrey et al. 1984, Noble et al. 1983, Uhnoo et al. 1990a, Sagher et al. 1991)
  • rotaviruses induce changes in the microcirculation of intestinal villi of neonatal mice (Osborne et al. 1991)
  • rotavirus infection alters intestinal absorption (Davidsson et al. 1977, Graham et al. 1984, Heyman et al. 1987, Ijaz et al. 1987, Salim et al. 1995, Katyal et al. 1999) and intestinal enzyme profiles (Collins et al. 1988, 1990, Jourdan et al. 1998, Katyal et al. 1999)
  • intestinal fluid and electrolyte secretion is enhanced through the effects of a viral enterotoxin NSP4 (Ball et al. 1996, Estes & Morris 1999) and by activation of the enteric nervous system (Lundgren et al. 2000)

Cell biology

  • rotavirus infection causes alterations in the polarized sorting of neuronal proteins (Weclewicz et al. 1993)
  • NSP4 increases intracellular calcium levels by release from the endoplasmic reticulum (Tian et al. 1994, 1995, Ball et al. 1996)
  • NSP4 alters plasma membrane permeability and may facilitate cell death (Tian et al. 1996, Newton et al. 1997)

Immunology

  • rotavirus infection causes recruitment and activation of CD4+ and CD8+ T cells (Offit & Dudzik 1989, Offit et al. 1992, McNeal et al. 1997, Rott et al. 1997) and a vigorous mucosal IgA response (Merchant et al. 1991, Coffin et al. 1995); resolution of rotavirus infection is due to both T (particularly CD8+ cells) and B cells, while protection against rotavirus is primarily dependent on antibodies (Ward 1996, Feng et al. 1997, McNeal et al. 1997, Franco & Greenberg 1999)
  • rotavirus infection induces a mixed Th1/Th2 pattern of cytokine production (IFN-g, IL-5, IL-10) by mouse spleen cells (Fromantin et al. 1998)
  • rotavirus infection leads to increased mRNA for several C-C and C-X-C chemokines and interferon-b in the mouse small intestine (Rollo et al. 1999)
  • Interactions with other infectious agents
  • a synergistic pathogenic effect between rotavirus and Escherichia coli occurs in infant mice (Newsome & Coney 1985) and weanling rabbits (Thouless et al. 1996)
  • infection of human enterocyte-like cells with rotavirus enhances invasiveness of Yersinia enterocolitica and Y. pseudotuberculosis (Di Biase et al. 2000)

References:

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Coffin SE, Klinek M, Offit PA (1995) Induction of virus-specific antibody production by lamina propria lymphocytes following intramuscular inoculation with rotavirus. Journal of Infectious Diseases 172, 874-8

Collins J, Candy DCA, Starkey WG, Spencer AJ, Osborne MP, Stephen J (1990) Disaccharidase activities in small intestine of rotavirus-infected suckling mice: a histochemical study. Journal of Pediatric Gastroenterology and Nutrition 11, 395-403

Collins J, Starkey WG, Walls TS, Clarke GJ, Worton KK, Spencer AJ, Haddon SJ, Osborne MP, Candy DCA, Stephen J (1988) Intestinal enzyme profiles in normal and rotavirus-infected mice. Journal of Pediatric Gastroenterology and Nutrition 7, 264-72

Davidsson GP, Gall DG, Petric M, Butler DG, Hamilton JR (1977) Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport. Journal of Clinical Investigation 60, 1402-9

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Graham DY, Sackman JW, Estes MK (1984) Pathogenesis of rotavirus-induced diarrhea. Preliminary studies in miniature swine piglet. Digestive Diseases and Sciences 29, 1028-35

Harkness JE, Wagner JE (1995) Rotavirus infections. In: The Biology and Medicine of Rabbits and Rodents. Baltimore: Williams & Wilkins, pp 280-2

Heyman M, Corthier G, Petit A, Meslin JC, Moreau C, Desjeux JF (1987) Intestinal absorption of macromolecules during viral enteritis: an experimental study on rotavirus-infected conventional and germ-free mice. Pediatric Research 22, 72-8

Ijaz MK, Sabara MI, Frenchick PJ, Babiuk LA (1987) Assessment of intestinal damage in rotavirus infected neonatal mice by a D-xylose absorption test. Journal of Virological Methods 18, 153-7

Jourdan N, Brunet JP, Sapin C, Blais A, Cotte-Laffitte J, Forestier F, Quero AM, Trugnan G, Servin AL (1998) Rotavirus infection reduces sucrase-isomaltase expression in human intestinal epithelial cells by perturbing protein targeting and organization of microvillar cytoskeleton. Journal of Virology 72, 7228-36

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Newton K, Meyer JC, Bellamy AR, Taylor JA (1997) Rotavirus nonstructural glycoprotein NSP4 alters plasma membrane permeability in mammalian cells. Journal of Virology 71, 9458-65

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Offit PA, Hoffenberg EJ, Pia ES, Panackal PA, Hill NL (1992) Rotavirus-specific helper T cell responses in newborns, infants, children, and adults. Journal of Infectious Diseases 165, 1107-11

Osborne MP, Haddon SJ, Worton KJ, Spencer AJ, Starkey WG, Thornber D, Stephen J (1991) Rotavirus-induced changes in the microcirculation of intestinal villi of neonatal mice in relation to the induction and persistence of diarrhea. Journal of Pediatric Gastroenterology and Nutrition 12, 111-20

Petersen C, Grasshoff S, Luciano L (1998) Diverse morphology of biliary atresia in an animal model. Journal of Hepatology 28, 603-7

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Ward RL, McNeal MM (1999) Adult mouse model for rotavirus. In: Handbook of Animal Models of Infection (Zak O, Sande MA, eds). San Diego: Academic Press, pp 1049-54

Weclewicz K, Svensson L, Bilger M, Holmberg K, Wallin M, Kristensson K (1993) Microtubule-associated protein 2 appears in axons of cultured dorsal root ganglia and spinal cord neurons after rotavirus infection. Journal of Neuroscience Research 36, 173-82

Willoughby RE (1993) Rotaviruses bind preferentially O-linked sialylglycoconjugates and sialomucins. Glycobiology 3, 437-45

Willoughby RE, Yolken RH, Schnaar RL (1990) Rotaviruses specifically bind to the neutral glycosphingolipid asialo-GM1. Journal of Virology 64, 4830

Author: Dr. Michael Mähler, Hannover