Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders

Bhupesh Prusty, Nitish Gulve, Sheila Govind, Gerhard Krueger, Julia Feichtinger, Lee Larcombe, Richard Aspinall, Dharam Ablashi, Carla Toro

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Abstract

Early-life infections and associated neuroinflammation is incriminated in the pathogenesis of various mood disorders. Infection with human roseoloviruses, HHV-6A and HHV-6B, allows viral latency in the central nervous system and other tissues, which can later be activated causing cognitive and behavioral disturbances. Hence, this study was designed to evaluate possible association of HHV-6A and HHV-6B activation with three different groups of psychiatric patients. DNA qPCR, immunofluorescence and FISH studies were carried out in post-mortem posterior cerebellum from 50 cases each of bipolar disorder (BPD), schizophrenia, 15 major depressive disorder (MDD) and 50 appropriate control samples obtained from two well-known brain collections (Stanley Medical Research Institute). HHV-6A and HHV-6B late proteins (indicating active infection) and viral DNA were detected more frequently (p < 0.001 for each virus) in human cerebellum in MDD and BPD relative to controls. These roseolovirus proteins and DNA were found less frequently in schizophrenia cases. Active HHV-6A and HHV-6B infection in cerebellar Purkinje cells were detected frequently in BPD and MDD cases. Furthermore, we found a significant association of HHV-6A infection with reduced Purkinje cell size, suggesting virus-mediated abnormal Purkinje cell function in these disorders. Finally, gene expression analysis of cerebellar tissue revealed changes in pathways reflecting an inflammatory response possibly to HHV-6A infection. Our results provide molecular evidence to support a role for active HHV-6A and HHV-6B infection in BPD and MDD.
Original languageEnglish
Article number1955
JournalFrontiers in Microbiology
Volume9
DOIs
Publication statusPublished - 21 Aug 2018

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Human Herpesvirus 6
Purkinje Cells
Mood Disorders
Infection
Major Depressive Disorder
Bipolar Disorder
Roseolovirus
Cerebellum
Schizophrenia
Virus Latency
Viruses
DNA
Viral DNA
Cell Size
Fluorescent Antibody Technique
Psychiatry
Biomedical Research
Proteins

Bibliographical note

Copyright © 2018 Prusty, Gulve, Govind, Krueger, Feichtinger, Larcombe, Aspinall, Ablashi and Toro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Keywords

  • Bipolar
  • Herpes Virus

Cite this

Prusty, B., Gulve, N., Govind, S., Krueger, G., Feichtinger, J., Larcombe, L., ... Toro, C. (2018). Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders. Frontiers in Microbiology, 9, [1955]. https://doi.org/10.3389/fmicb.2018.01955

Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders. / Prusty, Bhupesh; Gulve, Nitish; Govind, Sheila; Krueger, Gerhard ; Feichtinger, Julia; Larcombe, Lee ; Aspinall, Richard; Ablashi, Dharam ; Toro, Carla.

In: Frontiers in Microbiology, Vol. 9, 1955, 21.08.2018.

Research output: Contribution to journalArticle

Prusty, B, Gulve, N, Govind, S, Krueger, G, Feichtinger, J, Larcombe, L, Aspinall, R, Ablashi, D & Toro, C 2018, 'Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders' Frontiers in Microbiology, vol. 9, 1955. https://doi.org/10.3389/fmicb.2018.01955
Prusty B, Gulve N, Govind S, Krueger G, Feichtinger J, Larcombe L et al. Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders. Frontiers in Microbiology. 2018 Aug 21;9. 1955. https://doi.org/10.3389/fmicb.2018.01955
Prusty, Bhupesh ; Gulve, Nitish ; Govind, Sheila ; Krueger, Gerhard ; Feichtinger, Julia ; Larcombe, Lee ; Aspinall, Richard ; Ablashi, Dharam ; Toro, Carla. / Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders. In: Frontiers in Microbiology. 2018 ; Vol. 9.
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