Rotavirus NSP4 mediates an increase in the pro-inflammatory eicosanoid, prostaglandin E2, during infection.

Abstract

Rotavirus (RV) type A is a leading cause of severe infantile gastroenteritis globally. Studies show that prostaglandin E2 (PGE2) levels increase during RV infection, enhancing viral attachment and internalisation. However, the underlying mechanism for the increased PGE2 levels remains unclear. Using a plasmid-based reverse genetics system, we engineered a recombinant RV carrying mutations in the viroporin domain of NSP4 that decreased cytoplasmic calcium (Ca2+) conductivity. This resulted in decreased cytoplasmic phospholipase A2 (cPLA2) activity, the rate-limiting enzyme in PGE2 biosynthesis, and subsequently reduced PGE2 levels and viral yield. These findings are consistent with RV-induced PGE2 production occurring in a NSP4-cyto[Ca²⁺]-cPLA2-dependent manner.

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