title: Rotavirus induces a biphasic enterotoxic and cytotoxic response in human-derived intestinal enterocytes, which is inhibited by human immunoglobulins.
abstract: The mechanisms of diarrhea due to rotavirus infection in humans are not fully understood; no specific therapy is available, but orally administered human serum immunoglobulins are effective in blocking stool output. We aimed to investigate the effect of rotavirus on ion transport and the role of NSP4 in human-derived enterocytes, and to test the efficacy of human serum immunoglobulin in a model of rotavirus infection. Soon after infection, rotavirus induces active chloride secretion in enterocytes. This effect is evident before viral replication leads to cell damage and correlates with NSP4 production. Inhibition of NSP4 prevents the early secretory phase but not cell damage. Incubation with human serum immunoglobulin blocks both ion secretion and cell damage. Rotavirus exerts an early NSP4-dependent ion secretion and subsequent tissue damage. The combined enterotoxic and cytotoxic effects may be responsible for the increased severity of diarrhea due to rotavirus infection, and both are counteracted by human serum immunoglobulin.
authors: Department of Pediatrics, University Federico II of Naples, Naples, Italy.
authors: Giulio
authors: G
authors: De Marco
authors: Ileana
authors: I
authors: Bracale
authors: Vittoria
authors: V
authors: Buccigrossi
authors: Eugenia
authors: E
authors: Bruzzese
authors: Roberto Berni
authors: RB
authors: Canani
authors: Gaetano
authors: G
authors: Polito
authors: Franco Maria
authors: FM
authors: Ruggeri
authors: Alfredo
authors: A
authors: Guarino
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D018938:Caco-2 Cells; D016923:Cell Death; D002470:Cell Survival; D002712:Chlorides / Q000378:metabolism; D020895:Enterocytes / Q000502:physiology* / Q000821:virology*; D006023:Glycoproteins / Q000633:toxicity*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D017136:Ion Transport; D007477:Ions; D009500:Neutralization Tests; D010539:Permeability; D012401:Rotavirus / Q000472:pathogenicity*; D014118:Toxins, Biological / Q000633:toxicity*; D017361:Viral Nonstructural Proteins / Q000633:toxicity*
chemical_list: D000914:Antibodies, Viral; D002712:Chlorides; D006023:Glycoproteins; D007136:Immunoglobulins; D007477:Ions; C081369:NS28 protein, rotavirus; D014118:Toxins, Biological; D017361:Viral Nonstructural Proteins