Viperin protein expression inhibits the late stage of respiratory syncytial virus morphogenesis

- The viperin protein is detected in inclusion bodies in RSV-infected HEp2 cells.
- RSV infection is unaffected by endogenous viperin protein in HEp2 cells.
- RSV gene expression is not affected by early viperin protein expression.
- Viperin expression blocks a late stage in the RSV replication cycle.
- Viperin expression blocks RSV particle maturation and transmission.

We examined the effect of respiratory syncytial virus (RSV) infection on viperin protein expression in the permissive HEp2 and non-permissive RAW 264.7 macrophage cell lines. In RSV-infected HEp2 cells low levels of the viperin protein was localized to the virus-induced inclusion bodies and did not impair virus transmission in these cells. In contrast, RSV-infected RAW 264.7 cells increased expression of the STAT1 protein occurred at between 6 and 12 h post-infection, which coincided with the appearance of P-STAT1. A relatively high level of viperin protein expression was detected in infected RAW 264.7 cells, and it was extensively localized throughout the cytoplasm of infected cells. The effect of early viperin protein expression on RSV infection in cells that are normally permissive to RSV cultivation was examined by using either transient transfected HEp2 cells or stable transfected HeLa cells that expressed the viperin protein. The early expression of viperin in HeLa cells did not prevent virus infection, and no significant inhibitory effect on either virus protein expression or targeting of virus proteins to the cell surface was noted. However, while inclusion body formation was not inhibited, early viperin protein expression was associated with the inhibition of virus filament formation and reduced cell-to-cell virus transmission. Inhibition of virus filament formation was also observed in HEp2 cells expressing viperin. Collectively our data suggested that viperin impaired RSV transmission by inhibiting virus filament formation, providing a basis for its anti-virus activity in RSV-infected cells.