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Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
Published on: March 22, 2016
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.
Introduction:
The infectious hypothesis suggests that microbes like herpesviruses may play a role in the pathogenesis of Alzheimer's disease (AD) and other related dementias through methods that may include viral genome integration. The occurrence of herpesvirus genome integration in dementia patients has not been thoroughly characterized.
Methods:
Over 7500 total whole-genome sequences from control, frontotemporal dementia/amyotrophic lateral sclerosis spectrum, Lewy body dementia (LBD), multiple system atrophy (MSA), and AD cohorts were screened for the integration of pathogen genomes using the PathSeq computational tool.
Results:
Low PathSeq scores for human herpesvirus 6 (HHV-6) were consistent with the suspected integration of viral genome segments. The LBD and MSA cohorts had a significantly higher prevalence of this partial HHV-6 genome integration.
Discussion:
This higher prevalence in both synucleinopathies was not noted in other herpesviruses, suggesting that the integration of HHV-6 may play a role in a subset of these patients.
Highlights:
Over 7500 whole-genome sequences from controls and dementia patients were analyzed. Sequences consistent with integrated herpesviruses were identified using PathSeq. Prevalence of partial HHV-6 integration was higher in synucleinopathies. Herpesviruses genome integration may play a role in subsets of dementia patients.
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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