Statins enhance extracellular release of hepatitis C virus particles through ERK5 activation.

Autor: Aoki-Utsubo C; Department of Public Health, Graduate School of Health Sciences, Kobe University, Kobe, Japan., Kameoka M; Department of Public Health, Graduate School of Health Sciences, Kobe University, Kobe, Japan., Deng L; Division of Infectious Disease Control, Graduate School of Medicine, Kobe University, Kobe, Japan., Hanafi M; Research Center for Chemistry, National Research and Innovation Agency (BRIN), Serpong, Indonesia., Dewi BE; Department of Microbiology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia., Sudarmono P; Department of Microbiology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia., Wakita T; National Institute of Infectious Diseases, Tokyo, Japan., Hotta H; Department of Public Health, Graduate School of Health Sciences, Kobe University, Kobe, Japan.; Faculty of Clinical Nutrition and Dietetics, Konan Women's University, Kobe, Japan.
Jazyk: angličtina
Zdroj: Microbiology and immunology [Microbiol Immunol] 2024 Oct; Vol. 68 (10), pp. 359-370. Date of Electronic Publication: 2024 Jul 29.
DOI: 10.1111/1348-0421.13166
Abstrakt: Statins, such as lovastatin, have been known to inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Statins were reported to moderately suppress hepatitis C virus (HCV) replication in cultured cells harboring HCV RNA replicons. We report here using an HCV cell culture (HCVcc) system that high concentrations of lovastatin (5-20 μg/mL) markedly enhanced the release of HCV infectious particles (virion) in the culture supernatants by up to 40 times, without enhancing HCV RNA replication, HCV protein synthesis, or HCV virion assembly in the cells. We also found that lovastatin increased the phosphorylation (activation) level of extracellular-signal-regulated kinase 5 (ERK5) in both the infected and uninfected cells in a dose-dependent manner. The lovastatin-mediated increase of HCV virion release was partially reversed by selective ERK5 inhibitors, BIX02189 and XMD8-92, or by ERK5 knockdown using small interfering RNA (siRNA). Moreover, we demonstrated that other cholesterol-lowering statins, but not dehydrolovastatin that is incapable of inhibiting HMG-CoA reductase and activating ERK5, enhanced HCV virion release to the same extent as observed with lovastatin. These results collectively suggest that statins markedly enhance HCV virion release from infected cells through HMG-CoA reductase inhibition and ERK5 activation.
(© 2024 The Societies and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
Externí odkaz: