Herpes simplex virus type 1 infection induces activation and recruitment of protein kinase C to the nuclear membrane and increased phosphorylation of lamin B

We report that herpes simplex virus type 1 (HSV-1) infection leads to the recruitment of protein kinase C (PKC) to the nuclear rim. In HEp-2 cells, PKC recruitment to the nuclear rim was initiated between 8 h and 12 h postinfection. PKC delta, a proapoptotic kinase, was completely recruited to the nuclear rim upon infection with HSV-1. PKC alpha was less dramatically relocalized mostly at the nuclear rim upon infection, although some PKC alpha remained in the cytoplasm. PKC zeta-specific immunofluorescence was not significantly relocated to the nuclear rim. The U(L)34 and U(L)31 proteins, as well as their association, were each required for PKC recruitment to the nuclear rim. The HSV-1 U(S)3 protein product, a kinase which regulates the phosphorylation state and localization of UL34, was not required for PKC recruitment to the nuclear rim; however, it was required for proper localization along the nuclear rim, as PKC appeared unevenly distributed along the nuclear rim of cells infected with U(S)3 null and kinase-dead mutants. HSV-1 infection induced the phosphorylation of both lamin B and PKC. Elevated lamin B phosphorylation in HSV-1-infected cells was partially reduced by inhibitors of PKC. The data suggest a model in which kinases that normally disassemble the nuclear lamina during apoptosis are recruited to the nuclear membrane through functions requiring U(L)31 and U(L)34. We hypothesize that the recruitment of PKC functions to phosphorylate lamin B to help modify the nuclear lamina and promote budding of nucleocapsids at the inner nuclear membrane.