Herpes simplex virus requires poly(ADP-ribose) polymerase activity for efficient replication and induces extracellular signal-related kinase-dependent phosphorylation and ICP0-dependent nuclear localization of tankyrase 1

Zhuan Li, Yohei Yamauchi, Maki Kamakura, Tsugiya Murayama, Fumi Goshima, Hiroshi Kimura, Yukihiro Nishiyama

Research output: Contribution to journalArticle (Academic Journal)

35 Citations (Scopus)

Abstract

Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) which localizes to multiple subcellular sites, including telomeres and mitotic centrosomes. Poly(ADP-ribosyl)ation of the nuclear mitotic apparatus (NuMA) protein by tankyrase 1 during mitosis is essential for sister telomere resolution and mitotic spindle pole formation. In interphase cells, tankyrase 1 resides in the cytoplasm, and its role therein is not well understood. In this study, we found that herpes simplex virus (HSV) infection induced extensive modification of tankyrase 1 but not tankyrase 2. This modification was dependent on extracellular signal-regulated kinase (ERK) activity triggered by HSV infection. Following HSV-1 infection, tankyrase 1 was recruited to the nucleus. In the early phase of infection, tankyrase 1 colocalized with ICP0 and thereafter localized within the HSV replication compartment, which was blocked in cells infected with the HSV-1 ICP0-null mutant R7910. In the absence of infection, ICP0 interacted with tankyrase 1 and efficiently promoted its nuclear localization. HSV did not replicate efficiently in cells depleted of both tankyrases 1 and 2. Moreover, XAV939, an inhibitor of tankyrase PARP activity, decreased viral titers to 2 to 5% of control values. We concluded that HSV targets tankyrase 1 in an ICP0- and ERK-dependent manner to facilitate its replication.

Original languageEnglish
Pages (from-to)492-503
Number of pages12
JournalJournal of Virology
Volume86
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Animals
  • Cell Line
  • Cell Nucleus
  • Extracellular Signal-Regulated MAP Kinases
  • Herpes Simplex
  • Herpesvirus 1, Human
  • Humans
  • Immediate-Early Proteins
  • Phosphorylation
  • Protein Binding
  • Protein Transport
  • Tankyrases
  • Ubiquitin-Protein Ligases
  • Virus Replication
  • Journal Article

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