Herpes simplex virus type 1 induces nuclear accumulation of hyperphosphorylated tau in neuronal cells

J Neurosci Res. 2012 May;90(5):1020-9. doi: 10.1002/jnr.23003. Epub 2012 Jan 18.


Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that remains latent in host neurons. Viral DNA replication is a highly structured process in which the redistribution of nuclear proteins plays an important role. Although tau is most widely known as a microtubule-associated protein found in a hyperphosphorylated state in the brains of patients with Alzheimer's disease (AD), this protein has also been detected at other sites such as the nucleolus. Here, we establish that HSV-1 infection gives rise to an increase in tau phosphorylation and that hyperphosphorylated tau accumulates in the nucleus, forming defined structures in HSV-1-infected neuronal cells reminiscent of the common sites of viral DNA replication. When tau expression in human neuroblastoma cells was specifically inhibited using an adenoviral vector expressing a short hairpin RNA to tau, viral DNA replication was not affected, indicating that tau is not required for HSV-1 growth in neuronal cells. Given that HSV-1 is considered a risk factor for AD, our results suggest a new way in which to understand the relationships between HSV-1 infection and the pathogenic mechanisms leading to AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Viral / pharmacology
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Cell Nucleus / virology*
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cell Survival / physiology
  • Chlorocebus aethiops
  • DNA Replication
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Enzyme Inhibitors / pharmacology
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / immunology
  • Herpesvirus 1, Human / physiology*
  • Humans
  • Neuroblastoma / pathology
  • Phosphorylation / drug effects
  • Phosphorylation / physiology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Time Factors
  • Vero Cells / metabolism
  • Vero Cells / virology
  • Viral Plaque Assay
  • tau Proteins / metabolism*


  • Antibodies, Monoclonal
  • Antibodies, Viral
  • DNA, Viral
  • Enzyme Inhibitors
  • PHF-1 monoclonal antibody
  • RNA, Small Interfering
  • tau Proteins