Role of nitric oxide during rotavirus infection.
The pathophysiological mechanisms behind rotavirus-induced diarrhoea still remain incomplete. Current views suggest that the non-structural protein 4 (NSP4) of rotavirus and the enteric nervous system (ENS) participate in water secretion and diarrhoea. In the present work the role of nitric oxide (NO) in rotavirus infection and disease has been studied in vitro, mice and humans. Incubation of human intestinal epithelial cells (HT-29) with purified NSP4 but not with infectious virus produced NO2/NO3 accumulation in the incubation media. The NSP4-induced release of NO metabolites occurred within the first minutes after the addition of the toxin. Mice infected with murine rotavirus (strain EDIM) accumulated NO2/NO3 in the urine at the onset for diarrhoea. Following rotavirus infection, inducible nitric oxide synthetase (iNOS) mRNA was upregulated in ileum, but not in duodenum or jejunum of newborn pups within 5 days post-infection. A prospective clinical study including 46 children with acute rotavirus infection and age-matched controls concluded that rotavirus infection stimulates NO production during the course of the disease (P < 0.001). These observations identify NO as an important mediator of host responses during rotavirus infection.
Rodríguez-Díaz
Jesús
J
Department of Microbiology, School of Medicine, University of Valencia, Spain.
Banasaz
Mahanez
M
Istrate
Claudia
C
Buesa
Javier
J
Lundgren
Ove
O
Espinoza
Felix
F
Sundqvist
Tommy
T
Rottenberg
Martin
M
Svensson
Lennart
L
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D016022:Case-Control Studies; D002460:Cell Line; D005759:Gastroenteritis / Q000209:etiology / Q000378:metabolism; D006023:Glycoproteins / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012401:Rotavirus / Q000472:pathogenicity; D012400:Rotavirus Infections / Q000209:etiology / Q000378:metabolism*; D014118:Toxins, Biological / Q000633:toxicity; D017361:Viral Nonstructural Proteins / Q000633:toxicity
D006023:Glycoproteins; C081369:NS28 protein, rotavirus; D012333:RNA, Messenger; D014118:Toxins, Biological; D017361:Viral Nonstructural Proteins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse