Increased Mitochondrial Genetic Diversity in Persons Infected With Hepatitis C Virus.
OBJECTIVE
The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression.


METHODS
We evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing.


RESULTS
Results were as follows: (1) the average diversity among cases with seronegative acute HCV infection was 4.2 times higher than among uninfected controls; (2) the diversity level among cases with chronic HCV infection was 96.1 times higher than among uninfected controls; and (3) the diversity was 23.1 times higher among chronic than acute cases. In 2 patients who were followed up during combined interferon and ribavirin therapy, mtDNA nucleotide diversity decreased dramatically after the completion of therapy in both patients: by 100% in patient A after 54 days and by 70.51% in patient B after 76 days.


CONCLUSIONS
HCV infection strongly affects mtDNA genetic diversity. A rapid decrease in mtDNA genetic diversity observed after therapy-induced HCV clearance suggests that the effect is reversible, emphasizing dynamic genetic relationships between HCV and mitochondria. The level of mtDNA nucleotide diversity can be used to discriminate recent from past infections, which should facilitate the detection of recent transmission events and thus help identify modes of transmission.
Laboratory of Molecular Epidemiology and Bioinformatics, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
David S
DS
Campo
Laboratory of Molecular Epidemiology and Bioinformatics, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
Ha-Jung
HJ
Roh
Center for Hepatitis C, Atlanta Medical Center, Atlanta, Georgia; Medical College of Georgia, Augusta, Georgia; Emory School of Medicine, Atlanta, Georgia.
Brian L
BL
Pearlman
Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York.
Daniel S
DS
Fierer
Laboratory of Molecular Epidemiology and Bioinformatics, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
Sumathi
S
Ramachandran
Laboratory of Molecular Epidemiology and Bioinformatics, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
Gilberto
G
Vaughan
Center for Hepatitis C, Atlanta Medical Center, Atlanta, Georgia.
Andrew
A
Hinds
Laboratory of Molecular Epidemiology and Bioinformatics, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
Zoya
Z
Dimitrova
Laboratory of Molecular Epidemiology and Bioinformatics, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
Pavel
P
Skums
Laboratory of Molecular Epidemiology and Bioinformatics, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
Yury
Y
Khudyakov
AUC, area under the curve; Disease Biomarkers; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HVS, hypervariable segment; IFN, interferon; NGS, next-generation sequencing; Noninvasive; PCR, polymerase chain reaction; ROC, receiver operating characteristic; mtDNA; mtDNA, mitochondrial DNA; pegIFN, peginterferon