The Influence of Hepatitis C Virus Therapy on the DNA Base Excision Repair System of Peripheral Blood Mononuclear Cells

• Published in: DNA and cell biology Vol. 36; no. 7; p. 535
• Main Authors: Czarny, Piotr, Merecz-Sadowska, Anna, Majchrzak, Kinga, Jabłkowski, Maciej, Szemraj, Janusz, Śliwiński, Tomasz, Karwowski, Bolesław
• Format: Journal Article
• Language: English
• Published: United States 01.07.2017
• Subjects: Anilides - pharmacology; Antiviral Agents - pharmacology; Carbamates - pharmacology; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell Nucleus - virology; Deoxyuridine - metabolism; DNA - genetics; DNA - metabolism; DNA Breaks, Double-Stranded; DNA Glycosylases - genetics; DNA Glycosylases - metabolism; DNA Repair; DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism; Drug Therapy, Combination; Endonucleases - genetics; Endonucleases - metabolism; Gene Expression; Hepacivirus - drug effects; Hepacivirus - growth & development; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Host-Pathogen Interactions; Humans; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - virology; Macrocyclic Compounds - pharmacology; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - virology; Molecular Mimicry; Primary Cell Culture; Ribavirin - pharmacology; Ritonavir - pharmacology; Sulfonamides - pharmacology; Uracil - analogs & derivatives; Uracil - pharmacology; antiviral drugs; base excision repair; hepatitis C virus; lymphocytes; DNA repair
• ISSN: 1557-7430
• DOI: 10.1089/dna.2017.3653

Hepatitis C virus (HCV) can infect extrahepatic tissues, including lymphocytes, creating reservoir of the virus. Moreover, HCV proteins can interact with DNA damage response proteins of infected cells. In this article we investigated the influence of the virus infection and a new ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) anti-HCV therapy on the PBMCs (peripheral blood mononuclear cells, mainly lymphocytes) DNA base excision repair (BER) system. BER protein activity was analyzed in the nuclear and mitochondrial extracts (NE and ME) of PBMC isolated from patients before and after therapy, and from subjects without HCV, using modeled double-strand DNA, with 2'-deoxyuridine substitution as the DNA damage. The NE and ME obtained from patients before therapy demonstrated lower efficacy of 2'-deoxyuridine removal and DNA repair polymerization than those of the control group or patients after therapy. Moreover, the extracts from the patients after therapy had similar activity to those from the control group. However, the efficacy of apurinic/apyrimidinic site excision in NE did not differ between the studied groups. We postulate that infection of lymphocytes by the HCV can lead to a decrease in the activity of BER enzymes. However, the use of novel therapy results in the improvement of glycosylase activity as well as the regeneration of endonuclease and other crucial repair enzymes.