title: Herpes simplex virus type 1 induces nuclear accumulation of hyperphosphorylated tau in neuronal cells.
abstract: 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.
authors.affiliation: Departamento de Biología Molecular and Centro de Biología Molecular "Severo Ochoa"-CSIC-UAM, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Alvarez
authors.forename: Jesús
authors.initials: J
authors.lastname: Aldudo
authors.forename: María
authors.initials: M
authors.lastname: Alonso
authors.forename: Soraya
authors.initials: S
authors.lastname: Santana
authors.forename: Fernando
authors.initials: F
authors.lastname: Valdivieso
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000914:Antibodies, Viral / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002522:Chlorocebus aethiops; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014709:Vero Cells / Q000378:metabolism / Q000821:virology; D010948:Viral Plaque Assay; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D004279:DNA, Viral; D004791:Enzyme Inhibitors; C085349:PHF-1 monoclonal antibody; D034741:RNA, Small Interfering; D016875:tau Proteins