Herpes Simplex Virus Type 1 Infection Induces Activation and Recruitment of Protein Kinase C to the Nuclear Membrane and Increased Phosphorylation of Lamin B

Abstract

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. PKCδ, a proapoptotic kinase, was completely recruited to the nuclear rim upon infection with HSV-1. PKCα was less dramatically relocalized mostly at the nuclear rim upon infection, although some PKCα remained in the cytoplasm. PKCζ-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 U L 34, 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.