Requirement for Siva-1 for replication of influenza A virus through apoptosis induction.

Infection with influenza A virus causes acute respiratory tract infections in humans and may lead to lethal diseases including pneumonia. Identifying host factors that are involved in the severity of infectious diseases caused by influenza A virus is considered important for the prevention and treatment of these viral infections. This report demonstrated that Siva-1 is crucial for the induction of apoptosis caused by infection with influenza A virus and is involved in virus replication. Susceptibility to apoptosis induced by influenza A virus infection was increased in human lung-derived A549 cells, which stably express Siva-1. In addition, induction of apoptosis after influenza A virus infection was strongly inhibited by knockdown of Siva-1 expression. Furthermore, the replication of influenza A virus was significantly suppressed in A549 cells in which Siva-1 expression was inhibited and the effect of Siva-1 knockdown was eliminated by treatment with Z-VAD-FMK. These findings suggest that the caspase-dependent pathway for induction of apoptosis is involved in Siva-1-mediated influenza A virus replication.