Rotavirus is a major cause of diarrhea and vomiting, especially in children, which results in approximately 128,000 deaths annually.
The virus triggers the disease by infecting enterocyte cells in the small intestine, but only a fraction of the susceptible cells has the virus.
In the mid-90s, scientists proposed that the small portion of infected cells promotes severe disease by sending out signals that disrupt the normal function of neighboring uninfected cells, but the nature of the signal has remained a mystery.
In a new study, researchers discovered that rotavirus-infected cells release signaling molecules, identified as ADP, which binds its cellular receptor P2Y1 on neighboring cells.
Disrupting ADP binding to its receptor reduced the severity of diarrhea, suggesting that targeting the P2Y1 may be an effective strategy to control viral diarrhea in humans.
The research was conducted by a team at Baylor College of Medicine.
In the study, the researchers conducted the experiments using a lower dose of the virus and found that the infected cells could be triggering intercellular calcium waves in the uninfected cells.
The team also found previously unknown roles of ADP on rotavirus infection and replication, shining a spotlight on ADP as an important trigger of the multiple factors involved in severe diarrhea and vomiting caused by rotavirus.
They connected their finding to a concept proposed in the mid-90s that rotavirus-infected cells send signals to neighboring uninfected cells that disrupt their function, promoting diarrhea and vomiting.
They also showed that knocking out the P2Y1 gene, which prevents ADP from signaling, reduced the severity of rotavirus-induced diarrhea.
These findings add a new and very potent signaling pathway into the causative mechanisms of rotavirus diarrhea.
The team says in terms of treatment, currently, some drugs targeting P2Y1 are undergoing preclinical testing as anti-clotting drugs.
It’s possible that such drugs could be repurposed if proven to be safe for children, to be used to treat diarrhea caused by rotavirus infection.
One author of the study is Dr. Joseph Hyser, assistant professor of virology and microbiology.
The study is published in Science.
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