ArticlePloS one2013
Mutual antagonism between circadian protein period 2 and hepatitis C virus replication in hepatocytes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Circadian clock proteins BMAL1 and CLOCK regulate HSV-1 entry into nerve cells through NECTIN-1.Virology journal · 2025Article
- The role of circadian rhythm regulator PERs in oxidative stress, immunity, and cancer development.Cell communication and signaling : CCS · 2025Review
- Alterations in Circadian Rhythms, Sleep, and Physical Activity in COVID-19: Mechanisms, Interventions, and Lessons for the Future.Molecular neurobiology · 2024Review
- Heat-inactivated Streptococcus pneumoniae augments circadian clock gene expression in zebrafish cells.Scientific reports · 2024Article
- Crosstalk between circadian clocks and pathogen niche.PLoS pathogens · 2024Review
- Suppression of neuropathic pain in the circadian clock-deficientPNAS nexus · 2024Article
- Deficiency of histone variant macroH2A1.1 is associated with sexually dimorphic obesity in mice.Scientific reports · 2023Article
- Circadian mechanisms in adipose tissue bioenergetics and plasticity.Genes & development · 2023Review
- Monkeypox virus replication underlying circadian rhythm networks.Journal of neurovirology · 2023Review
- When the clock ticks wrong with COVID-19.Clinical and translational medicine · 2022Review
- GDF11 inhibits adipogenesis and improves mature adipocytes metabolic function via WNT/β-catenin and ALK5/SMAD2/3 pathways.Cell proliferation · 2022Article
- Immunity, Infection, and the Zebrafish Clock.Infection and immunity · 2022Review
- The role of circadian clock pathways in viral replication.Seminars in immunopathology · 2022Review
- The Circadian Clock and Viral Infections.Journal of biological rhythms · 2021Review
- The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma.Oxidative medicine and cellular longevity · 2021Review
- Article
- The Circadian Clock, the Immune System, and Viral Infections: The Intricate Relationship Between Biological Time and Host-Virus Interaction.Pathogens (Basel, Switzerland) · 2020Review
- For Whom the Clock Ticks: Clinical Chronobiology for Infectious Diseases.Frontiers in immunology · 2020Review
- Molecular Interactions between Pathogens and the Circadian Clock.International journal of molecular sciences · 2019Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatitis C virus (HCV) infects approximately 3% of the world population and is the leading cause of liver disease, impacting hepatocyte metabolism, depending on virus genotype. Hepatic metabolic functions show rhythmic fluctuations with 24-h periodicity (circadian), driven by molecular clockworks ticking through translational-transcriptional feedback loops, operated by a set of genes, called clock genes, encoding circadian proteins. Disruption of biologic clocks is implicated in a variety of disorders including fatty liver disease, obesity and diabetes. The relation between HCV replication and the circadian clock is unknown.
methodsWe investigated the relationship between HCV core infection and viral replication and the expression of clock genes (Rev-Erbα, Rorα, ARNTL, ARNTL2, CLOCK, PER1, PER2, PER3, CRY1 and CRY2) in two cellular models, the Huh-7 cells transiently expressing the HCV core protein genotypes 1b or 3a, and the OR6 cells stably harboring the full-length hepatitis C genotype 1b replicon, and in human liver biopsies, using qRT-PCR, immunoblotting, luciferase assays and immunohistochemistry.
resultsIn Huh-7 cells expressing the HCV core protein genotype 1b, but not 3a, and in OR6 cells, transcript and protein levels of PER2 and CRY2 were downregulated. Overexpression of PER2 led to a consistent decrease in HCV RNA replicating levels and restoration of altered expression pattern of a subset of interferon stimulated genes (ISGs) in OR6 cells. Furthermore, in liver biopsies from HCV genotype 1b infected patients, PER2 was markedly localized to the nucleus, consistent with an auto-inhibitory transcriptional feedback loop.
conclusionsHCV can modulate hepatic clock gene machinery, and the circadian protein PER2 counteracts viral replication. Further understanding of circadian regulation of HCV replication and rhythmic patterns of host-hosted relationship may improve the effectiveness of HCV antiviral therapy. This would extend to hepatic viral infections the current spectrum of chronotherapies, implemented to treat metabolic, immune related and neoplastic disease.
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