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

• Published in: Journal of neuroscience research 2012-05, Vol.90 (5), p.1020-1029
• Main Authors: Álvarez, Gema, Aldudo, Jesús, Alonso, María, Santana, Soraya, Valdivieso, Fernando
• Format: Article
• Language: English
• Subjects: 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; Cercopithecus aethiops; DNA Replication; DNA, Viral - genetics; DNA, Viral - metabolism; Enzyme Inhibitors - pharmacology; Herpesvirus 1, Human - genetics; Herpesvirus 1, Human - immunology; Herpesvirus 1, Human - physiology; HSV-1; Humans; infection; Neuroblastoma - pathology; neurodegeneration; phosphorylation; Phosphorylation - drug effects; Phosphorylation - physiology; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; tau Proteins - metabolism; Time Factors; Vero Cells - metabolism; Vero Cells - virology; Viral Plaque Assay
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.23003

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. © 2012 Wiley Periodicals, Inc.