title: Rotavirus NSP486-175interacts with H9c2(2-1) cells in vitro, elevates intracellular Ca2+levels and can become cytotoxic: a possible mechanism for extra-intestinal pathogenesis.
abstract: Rotavirus (RV) is the predominant cause of infantile gastroenteritis with multiple pathogenic factors, among which enterotoxin NSP4 is the most significant factor. NSP4 has been shown to induce elevation of the intracellular calcium concentration, alteration of the cytoskeleton organization, and cytopathic effect among other processes. However, increasing evidence suggests that RVs can escape from the gastrointestinal tract and invade other organs and tissues to cause extra-intestinal diseases. In this study, we investigated whether NSP4 has a pathogenic effect on extra-intestinal cells and examined possible molecular mechanisms in vitro. Our results showed that NSP486-175has important functions in increasing intracellular Ca2+concentration, altering actin cytoskeleton organization and inducing cellular damage in H9c2(2-1) cells. Blockade of the integrin α2 receptor using a specific antibody attenuated the increase of intracellular Ca2+concentration and alleviated the observed cytopathic effects, suggesting that integrin α2 may be a receptor for NSP486-175. Collectively, these results indicate that extracellular NSP486-175can induce elevation of the intracellular Ca2+concentration, cause cytotoxic changes, and disrupt the actin cytoskeleton in H9c2(2-1) cells, which may constitute a possible mechanism for RV extra-intestinal pathogenesis.
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People's Republic of China.
authors.forename: Xiaoshun
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People's Republic of China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People's Republic of China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People's Republic of China. wz88816290@163.com.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Li
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics* / Q000473:pathology; D000818:Animals; D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000473:pathology / Q000821:virology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000473:pathology / Q000821:virology; D012401:Rotavirus / Q000235:genetics* / Q000472:pathogenicity; D012400:Rotavirus Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D014118:Toxins, Biological / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; C081369:NS28 protein, rotavirus; D014118:Toxins, Biological; D017361:Viral Nonstructural Proteins; D002118:Calcium
keywords: Cytopathic effect; Cytoskeleton; Extra-intestinal pathogenesis; Intracellular Ca2+ concentration; NSP4