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The life cycle of the hepatitis C virus (HCV) can be divided into several stages, including viral entry, protein translation, RNA replication, viral assembly, and release. HCV genomic RNA replication occurs in the replication organelles (RO) and is tightly linked to ER membrane alterations containing replication complexes (proteins NS3 to NS5B). The amplification of HCV genomic RNA could be regulated by the RO biogenesis, the viral RNA structure (i.e., cis-acting replication elements), and both viral and cellular proteins. Studies on HCV replication have led to the development of direct-acting antivirals (DAAs) targeting the replication complex. This review article summarizes the viral and cellular factors involved in regulating HCV genomic RNA replication and the DAAs that inhibit HCV replication.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004249 | PMC |
http://dx.doi.org/10.3390/v13030520 | DOI Listing |
J Virol
September 2025
Department of Microbiology and Immunology, Center for Pathogen Research, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Unlabelled: There is a need for the development of broad-spectrum antiviral compounds that can act as first-line therapeutic countermeasures to emerging viral infections. Host-directed approaches present a promising avenue of development and carry the benefit of mitigating risks of viral escape mutants. We have previously found the SKI (super killer) complex to be a broad-spectrum, host-target with our lead compound ("UMB18") showing activity against influenza A virus, coronaviruses, and filoviruses.
View Article and Find Full Text PDFJ Virol
September 2025
Université catholique de Louvain, de Duve Institute, Brussels, Belgium.
Unrelated pathogens, including viruses and bacteria, use a common short linear motif (SLiM) to interact with cellular kinases of the RSK (p90 S6 ribosomal kinase) family. Such a "DDVF" (D/E-D/E-V-F) SLiM occurs in the leader (L) protein encoded by picornaviruses of the genus , including Theiler's murine encephalomyelitis virus (TMEV), Boone cardiovirus (BCV), and Encephalomyocarditis virus (EMCV). The L-RSK complex is targeted to the nuclear pore, where RSK triggers FG-nucleoporins hyperphosphorylation, thereby causing nucleocytoplasmic trafficking disruption.
View Article and Find Full Text PDFJ Virol
September 2025
Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, China.
Unlabelled: Cholesterol 25-hydroxylase (CH25H), an interferon-stimulated gene (ISG), has been implicated in broad-spectrum antiviral immunity. Here, we identify CH25H as a potent suppressor of hepatitis B virus (HBV) replication that significantly outperforms IFN-α in reducing HBV DNA, pregenomic RNA (pgRNA), HBsAg, and HBeAg, without inducing cytotoxicity. However, CH25H is weakly expressed in hepatocytes and only modestly induced by type I interferon.
View Article and Find Full Text PDFFront Microbiol
August 2025
College of Life Sciences, Hebei University, Baoding, China.
Introduction: The Zika virus (ZIKV) envelope (E) protein is critical for viral replication and host interactions. Although glycosylation of the E protein is known to influence viral infectivity and immune evasion, the specific functional roles of E protein glycosylation in ZIKV infectivity in mosquito cells remain unclear.
Methods: In this study, we generated a deglycosylation mutant ZIKV with a T156I substitution in the E protein and investigated its effects on viral replication and viral-host interactions in mosquito C6/36 cells.
Front Vet Sci
August 2025
Institute of Veterinary Medicine and Immunology, Sichuan Agricultural University, Chengdu, Sichuan, China.
Kunjin virus (KUNV), a naturally attenuated strain of West Nile virus (WNV), shares similar transmission modes and hosts-primarily mosquitoes, birds, and horses. Globally, reverse genetics is the principal methodology for characterizing the molecular etiology of flaviviruses. In this study, cytomegalovirus (CMV) promoter-driven KUNV reporter replicons were engineered to incorporate three distinct reporter genes: Nanoluc, oxGFP, and mCherry.
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