Influenza A Virus Replication Induces Cell Cycle Arrest in G 0 /G 1 Phase

Abstract

ABSTRACT Many viruses interact with the host cell division cycle to favor their own growth. In this study, we examined the ability of influenza A virus to manipulate cell cycle progression. Our results show that influenza A virus A/WSN/33 (H1N1) replication results in G 0 /G 1 -phase accumulation of infected cells and that this accumulation is caused by the prevention of cell cycle entry from G 0 /G 1 phase into S phase. Consistent with the G 0 /G 1 -phase accumulation, the amount of hyperphosphorylated retinoblastoma protein, a necessary active form for cell cycle progression through late G 1 into S phase, decreased after infection with A/WSN/33 (H1N1) virus. In addition, other key molecules in the regulation of the cell cycle, such as p21, cyclin E, and cyclin D1, were also changed and showed a pattern of G 0 /G 1 -phase cell cycle arrest. It is interesting that increased viral protein expression and progeny virus production in cells synchronized in the G 0 /G 1 phase were observed compared to those in either unsynchronized cells or cells synchronized in the G 2 /M phase. G 0 /G 1 -phase cell cycle arrest is likely a common strategy, since the effect was also observed in other strains, such as H3N2, H9N2, PR8 H1N1, and pandemic swine H1N1 viruses. These findings, in all, suggest that influenza A virus may provide favorable conditions for viral protein accumulation and virus production by inducing a G 0 /G 1 -phase cell cycle arrest in infected cells.