Spontaneous release of stable viral double-stranded RNA into the extracellular medium by influenza virus-infected MDCK epithelial cells: implicationsfor the viral acute phase response

The viral factor responsible for triggering the acute phase response, or 'f lu' syndrome, associated with many acute viral infections is not defined. O ne candidate viral factor is double-stranded RNA (dsRNA) generated during v iral replication. In this report we demonstrate by reverse-transcriptase po lymerase-chain reaction that nuclease-stable viral RNA was released from in fluenza-infected MDCK epithelial cells at the time of cell lysis. Removal o f virion-associated RNA by ultracentrifugation left equal amounts of positi ve-and negative-strand viral RNA in the medium that resisted degradation by endogenous RNase in the medium and by exogenous RNase added prior to pheno l extraction. These data are the first demonstration that viral RNA with ch aracteristics of dsRNA is spontaneously released from dying influenza virus -infected cells, and thus is available to amplify cytokine induction and co ntribute to systemic disease.