Herpesvirus genome integration in whole-genome sequences of dementia and control cohorts

Stacey L Piotrowski1, Mary Alice Allnutt1, Kory Johnson2

  • 1Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

Insights

Herpesvirus genome integration, particularly human herpesvirus 6 (HHV-6), was investigated in dementia patients. A higher prevalence of HHV-6 integration was found in Lewy body dementia and multiple system atrophy, suggesting a potential role in these synucleinopathies.

Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Genomics

Background:

  • The infectious hypothesis proposes herpesviruses contribute to Alzheimer's disease (AD) and dementia pathogenesis via viral genome integration.
  • The prevalence of herpesvirus genome integration in dementia patients remains under-characterized.

Purpose of the Study:

  • To investigate the occurrence and prevalence of herpesvirus genome integration in various dementia cohorts.
  • To determine if viral genome integration is associated with specific neurodegenerative diseases.

Main Methods:

  • Whole-genome sequences from over 7500 individuals (controls and dementia patients) were analyzed.
  • The PathSeq computational tool was employed to screen for integrated pathogen genomes.
  • Cohorts included Alzheimer's disease, frontotemporal dementia/amyotrophic lateral sclerosis spectrum, Lewy body dementia (LBD), and multiple system atrophy (MSA).

Main Results:

  • Sequences consistent with integrated herpesviruses were identified.
  • A significantly higher prevalence of partial human herpesvirus 6 (HHV-6) genome integration was observed in LBD and MSA cohorts.
  • This increased prevalence of HHV-6 integration was specific to synucleinopathies and not observed with other herpesviruses.

Conclusions:

  • The findings suggest that HHV-6 genome integration may play a role in a subset of patients with LBD and MSA.
  • Herpesvirus genome integration is a potential factor in the pathogenesis of certain neurodegenerative diseases.

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