Researchers have improved our understanding of how rotavirus, the most common cause of acute gastroenteritis in children, makes people sick.
The study is among the first to show that the rotavirus protein NSP4 is both necessary and sufficient for multiple aspects of rotavirus infection by disrupting calcium signaling not only within infected cells but also in nearby uninfected cells. These disruptions in calcium signaling affect rotavirus disease severity, providing new insights into how NSP4's function influences rotavirus virulence.
In the current study, Hyser and his colleagues looked deeper into how functions of NSP4 during rotavirus infection contribute to disease severity in hopes of finding a novel approach to treat or prevent the disease. In a previous study, the researchers discovered that rotavirus triggers aberrant calcium signals known as 'intercellular calcium waves' that radiate from infected cells to neighboring uninfected cells and that inhibition of these signals lessened disease severity.
The researchers found that the ability of rotavirus to generate calcium waves was fully attributable to NSP4, such that expression of NSP4 in cells, even in the absence of rotavirus infection, generated calcium waves indistinguishable from a native infection. Furthermore, calcium waves also triggered an immune response, implicating calcium dysregulation as a means of viral recognition.
Other contributors to this work include J. Thomas Gebert, Francesca J. Scribano, Kristen A. Engevik, Ethan M. Huleatt, Michael R. Eledge, Lauren E. Dorn, Asha A. Philip, Takahiro Kawagishi, Harry B. Greenberg and John T. Patton. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Indiana University and Stanford University School of Medicine.
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