Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9
In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regula...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-09-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396417303377 |
| _version_ | 1818034847909675008 |
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| author | Anastasia Hyrina Andrea D. Olmstead Paul Steven Mel Krajden Edward Tam François Jean |
| author_facet | Anastasia Hyrina Andrea D. Olmstead Paul Steven Mel Krajden Edward Tam François Jean |
| author_sort | Anastasia Hyrina |
| collection | DOAJ |
| description | In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n = 72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR), whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis — circulating miR-24, miR-223 and PCSK9 — whose regulation is affected by HCV infection and treatment-based viral cure. |
| first_indexed | 2024-12-10T06:45:40Z |
| format | Article |
| id | doaj.art-caa5f4c18f7441c4873a070f92ecc254 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-10T06:45:40Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-caa5f4c18f7441c4873a070f92ecc2542022-12-22T01:58:40ZengElsevierEBioMedicine2352-39642017-09-0123C687810.1016/j.ebiom.2017.08.020Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9Anastasia Hyrina0Andrea D. Olmstead1Paul Steven2Mel Krajden3Edward Tam4François Jean5Dept. of Microbiology and Immunology, University of British Columbia, CanadaDept. of Microbiology and Immunology, University of British Columbia, CanadaQIAGEN, United KingdomBCCDC Public Health Microbiology and Reference Laboratory, CanadaLAIR Centre, CanadaDept. of Microbiology and Immunology, University of British Columbia, CanadaIn patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n = 72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR), whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis — circulating miR-24, miR-223 and PCSK9 — whose regulation is affected by HCV infection and treatment-based viral cure.http://www.sciencedirect.com/science/article/pii/S2352396417303377Hepatitis C virusAntiviral therapymiR-24miR-122miR-223Proprotein convertase subtilisin/kexin type 9 |
| spellingShingle | Anastasia Hyrina Andrea D. Olmstead Paul Steven Mel Krajden Edward Tam François Jean Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9 EBioMedicine Hepatitis C virus Antiviral therapy miR-24 miR-122 miR-223 Proprotein convertase subtilisin/kexin type 9 |
| title | Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9 |
| title_full | Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9 |
| title_fullStr | Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9 |
| title_full_unstemmed | Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9 |
| title_short | Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9 |
| title_sort | treatment induced viral cure of hepatitis c virus infected patients involves a dynamic interplay among three important molecular players in lipid homeostasis circulating microrna mir 24 mir 223 and proprotein convertase subtilisin kexin type 9 |
| topic | Hepatitis C virus Antiviral therapy miR-24 miR-122 miR-223 Proprotein convertase subtilisin/kexin type 9 |
| url | http://www.sciencedirect.com/science/article/pii/S2352396417303377 |
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