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Increased Mitochondrial Genetic Diversity in Persons Infected With Hepatitis C Virus
David S Campo1, Ha-Jung Roh1, Brian L Pearlman2
1Laboratory of Molecular Epidemiology and Bioinformatics, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
Cellular and Molecular Gastroenterology and Hepatology
|February 9, 2017
Summary
Hepatitis C virus (HCV) infection significantly increases mitochondrial DNA (mtDNA) genetic diversity. This diversity rapidly decreases after successful HCV therapy, suggesting a reversible effect and aiding in identifying recent infections.
Area of Science:
- Virology
- Genetics
- Immunology
Background:
- Host genetics influence Hepatitis C virus (HCV) infection outcomes.
- HCV infection is linked to mitochondrial dysfunction and disease progression.
- Mitochondrial DNA (mtDNA) genetic diversity in the liver is associated with disease progression.
Purpose of the Study:
- To investigate the impact of HCV infection on host mtDNA genetic diversity.
- To assess the reversibility of HCV-induced mtDNA diversity changes after therapy.
- To determine if mtDNA diversity can differentiate recent from past HCV infections.
Main Methods:
- Evaluated genetic diversity of two mtDNA regions (hypervariable segments 1 and 2).
- Utilized next-generation sequencing on sera from 116 individuals.
- Analyzed mtDNA diversity in acute HCV, chronic HCV, and uninfected control groups.
Main Results:
- mtDNA diversity was 4.2x higher in acute HCV and 96.1x higher in chronic HCV cases compared to controls.
- Diversity was 23.1x higher in chronic compared to acute HCV cases.
- mtDNA nucleotide diversity decreased significantly (70.51-100%) after therapy-induced HCV clearance in two patients.
Conclusions:
- HCV infection significantly elevates host mtDNA genetic diversity.
- The observed decrease in mtDNA diversity post-therapy suggests a reversible effect of HCV on mitochondria.
- mtDNA nucleotide diversity levels can aid in distinguishing recent from past HCV infections, facilitating transmission event detection.
Keywords:
AUC, area under the curveDisease BiomarkersHCC, hepatocellular carcinomaHCV, hepatitis C virusHIV, human immunodeficiency virusHVS, hypervariable segmentIFN, interferonNGS, next-generation sequencingNoninvasivePCR, polymerase chain reactionROC, receiver operating characteristicmtDNAmtDNA, mitochondrial DNApegIFN, peginterferonRelated Concept Videos
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