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Herpes simplex virus type 1 induces nuclear accumulation of hyperphosphorylated tau in neuronal cells
Author(s) -
Álvarez Gema,
Aldudo Jesús,
Alonso María,
Santana Soraya,
Valdivieso Fernando
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23003
Subject(s) - herpes simplex virus , nucleolus , neurotropic virus , viral replication , biology , virology , virus , tauopathy , tau protein , dna replication , nuclear transport , viral protein , phosphorylation , dna , cell nucleus , microbiology and biotechnology , nucleus , neurodegeneration , alzheimer's disease , genetics , disease , medicine , pathology
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.