Age-Dependent Diarrhea Induced by a Rotaviral Nonstructural Glycoprotein

Ball, Joseph A.; Tian, Peng; Zeng, Chi; Morris, Andrew P.; Estes, Mary K.

doi:10.1126/science.272.5258.101

Cited by 629 publications

(530 citation statements)

References 33 publications

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“…Ball et al, (1996) have reported that mutation at position 131 has effect on the enterotoxic properties of the protein.…”

Section: Positive Selection At Position 131mentioning

confidence: 99%

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Molecular characterization of the rotavirus enterotoxin NSP4 gene of strains causing diarrhoea in children aged 0-5 years in northern India

Srivastava¹,

Jain²,

Khan³

et al. 2015

J App Pharm Sci

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Non structural protein 4 (NSP4) gene of Rotavirus encodes a multifunctional protein which has significant role in viral multiplication and pathogenesis of acute watery diarrhoea associated with rotaviral gastroenteritis. It is known as the first viral enterotoxin and mutations of the gene have been linked to altered pathogenesis. This study was planned to ascertain the genotypes and genetic variations of NSP4 gene in the rotavirus strains prevalent in this area. We collected consecutive diarrhoeal stools from equal no of children aged under five years hospitalized with diarrhoea in a period from January 2010 to June 2012 and tested them for rotavirus antigen by ELISA. NSP4 gene was amplified by RT-PCR and subsequently sequenced (Big-Dye terminator kit using 3130 ABI, Genetic analyzer) and genotyped by Rotavirus C software. Of the 260 samples, 58(22.3%) samples were positive by ELISA. We were able to amplify NSP4 gene by RTPCR from 45 strains of which 35 amplicons were selected for sequencing. Total 25(71.4%) strains belonged to genotype E1, 6 (17.1%) strains to genotype E2 and 4 (11.4%) matched with the genotype E6. Sequence analysis revealed changes in the nucleotides causing punctate mutations in the conserved regions, the Inter species variable domain (ISVD) and the enterotoxin region (amino acid 114-135). On evolutionary analysis of 33 strains amino acid at position 131 was found under positive selection.

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“…Ball et al, (1996) have reported that mutation at position 131 has effect on the enterotoxic properties of the protein.…”

Section: Positive Selection At Position 131mentioning

confidence: 99%

“…Initially this 175 aa protein was found to work as a receptor for immature double layered virion entering the endoplasmic reticulum for final maturation (Bergman et al, 1989). Later Ball et al, (1996) demonstrated that purified NSP4…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of the rotavirus enterotoxin NSP4 gene of strains causing diarrhoea in children aged 0-5 years in northern India

Srivastava¹,

Jain²,

Khan³

et al. 2015

J App Pharm Sci

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“…It has also recently been established that rotaviruses, an important cause of diarrhea in young children, produce diarrhea as a consequence of one of their nonstructural proteins, NSP4, stimulating phospholipase C, leading to increased intracellular free Ca 2ϩ in the gut mucosa (18)(19)(20). Thus, it occurred to us that the fluid accumulation in the respiratory tract associated with respiratory infections may be caused by altered epithelial transport.…”

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confidence: 99%

Influenza virus inhibits amiloride-sensitive Na⁺channels in respiratory epithelia

Kunzelmann

Beesley

King

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

109

124

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Many pathogens causing diarrhea do so by modulating ion transport in the gut. Respiratory pathogens are similarly associated with disturbances of fluid balance in the respiratory tract, although it is not known whether they too act by altering epithelial ion transport. Here we show that influenza virus A͞PR͞8͞34 inhibits the amiloride-sensitive Na ؉ current across mouse tracheal epithelium with a half-time of about 60 min. We further show that the inhibitory effect of the influenza virus is caused by the binding of viral hemagglutinin to a cell-surface receptor, which then activates phospholipase C and protein kinase C. Given the importance of epithelial Na ؉ channels in controlling the amount of fluid in the respiratory tract, we suggest that down-regulation of Na ؉ channels induced by influenza virus may play a role in the fluid transport abnormalities that are associated with influenza infections.hemagglutinin ͉ protein kinase C ͉ ENaC ͉ phospholipase C

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“…Nonstructural glycoprotein NSP4, encoded by gene segment lOin most strains, has captured much attention since SA 11 NSP4 was reported to induce diarrhea in neonatal mice (2). This viral enterotoxin hypothesis is confirmed and extended by the observation that murine rotavirus NSP4, which is phylogenetically distinct from SA 11 and other mammalian rotavirus NSP4 proteins (4,8), also caused diarrhea in the homologous *Address correspondence to Dr. Osamu Nakagomi, Department of Microbiology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita 01(}--8543, Japan.…”

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confidence: 99%

A Lack of Consistent Amino Acid Substitutions in NSP4 between Rotaviruses Derived from Diarrheal and Asymptomatically‐Infected Kittens

Oka

Nakagomi

2001

Microbiology and Immunology

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Nonstructural glycoprotein NSP4 of group A rotavirus has recently been shown to be a viral enterotoxin, inducing diarrhea in neonatal mice. Literature is conflicting as to whether there is any consistent amino acid substitution between virulent (or symptomatic) and attenuated (or asymptomatic) rotavirus strains. We have sequenced and compared the NSP4 sequences derived from a total of 10 geographicallyand serologically-related feline rotavirus strains from both diarrheal and asymptomatically-infected kittens. These NSP4 sequences were closely related to each other and there were differences at 19 amino acid residues, but none was segregated according to whether the strain was isolated from a diarrheal kitten or not. Thus, this study failed to lend support to the contention that mutations in NSP4 playa significant role in the pathogenesis of rotavirus diarrhea. Involvement of other genes may explain the outcome of infection in cats from which these 10 feline rotaviruses were isolated.

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Age-Dependent Diarrhea Induced by a Rotaviral Nonstructural Glycoprotein

Cited by 629 publications

References 33 publications

Molecular characterization of the rotavirus enterotoxin NSP4 gene of strains causing diarrhoea in children aged 0-5 years in northern India

Molecular characterization of the rotavirus enterotoxin NSP4 gene of strains causing diarrhoea in children aged 0-5 years in northern India

Influenza virus inhibits amiloride-sensitive Na⁺channels in respiratory epithelia

A Lack of Consistent Amino Acid Substitutions in NSP4 between Rotaviruses Derived from Diarrheal and Asymptomatically‐Infected Kittens

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Age-Dependent Diarrhea Induced by a Rotaviral Nonstructural Glycoprotein

Cited by 629 publications

References 33 publications

Molecular characterization of the rotavirus enterotoxin NSP4 gene of strains causing diarrhoea in children aged 0-5 years in northern India

Molecular characterization of the rotavirus enterotoxin NSP4 gene of strains causing diarrhoea in children aged 0-5 years in northern India

Influenza virus inhibits amiloride-sensitive Na+channels in respiratory epithelia

A Lack of Consistent Amino Acid Substitutions in NSP4 between Rotaviruses Derived from Diarrheal and Asymptomatically‐Infected Kittens

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Influenza virus inhibits amiloride-sensitive Na⁺channels in respiratory epithelia