p32 Is a Novel Target for Viral Protein ICP34.5 of Herpes Simplex Virus Type 1 and Facilitates Viral Nuclear Egress

• Published in: The Journal of biological chemistry 2014-12, Vol.289 (52), p.35795-35805
• Main Authors: Wang, Yu, Yang, Yin, Wu, Songfang, Pan, Shuang, Zhou, Chaodong, Ma, Yijie, Ru, Yongxin, Dong, Shuxu, He, Bin, Zhang, Cuizhu, Cao, Youjia
• Format: Article
• Language: English
• Subjects: Animals; Carrier Proteins - metabolism; Cell Nucleus - virology; Chlorocebus aethiops; HEK293 Cells; HeLa Cells; Herpesvirus; Herpesvirus 1, Human - physiology; Host-Pathogen Interactions; HSV; Humans; ICP34.5; Lamin B Receptor; Mitochondrial Proteins - metabolism; Molecular Bases of Disease; Nuclear Lamina; Nuclear Membrane; p32 (gC1qR/HABP1); Protein Interaction Mapping; Protein Transport; Protein-Protein Interaction; Receptors, Cytoplasmic and Nuclear - metabolism; Vero Cells; Viral Egress; Viral Protein; Viral Proteins - metabolism; Virus Release
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M114.603845

As a large double-stranded DNA virus, herpes simplex virus type 1 (HSV-1) assembles capsids in the nucleus where the viral particles exit by budding through the inner nuclear membrane. Although a number of viral and host proteins are involved, the machinery of viral egress is not well understood. In a search for host interacting proteins of ICP34.5, which is a virulence factor of HSV-1, we identified a cellular protein, p32 (gC1qR/HABP1), by mass spectrophotometer analysis. When expressed, ICP34.5 associated with p32 in mammalian cells. Upon HSV-1 infection, p32 was recruited to the inner nuclear membrane by ICP34.5, which paralleled the phosphorylation and rearrangement of nuclear lamina. Knockdown of p32 in HSV-1-infected cells significantly reduced the production of cell-free viruses, suggesting that p32 is a mediator of HSV-1 nuclear egress. These observations suggest that the interaction between HSV-1 ICP34.5 and p32 leads to the disintegration of nuclear lamina and facilitates the nuclear egress of HSV-1 particles.HSV disrupts nuclear lamina for release from nucleus during productive infection. A cellular protein, p32, contributes to the release of HSV from nucleus. p32 is hijacked by viral protein ICP34.5 to facilitate HSV nuclear egress and growth. The discovery of a novel target for viral protein provides insight for viral propagation.