ArticleEBioMedicine2019
Platelet factor 4 promotes rapid replication and propagation of Dengue and Japanese encephalitis viruses.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- Beyond Hemostasis: Platelet Biomarkers and Vascular-Immune Crosstalk in Dengue.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Clinical characteristics of thrombocytopenia in tropical diseases and management in resource-limited settings.Research and practice in thrombosis and haemostasis · 2026Review
- Modulatory effects of platelet-rich plasma on viral kinetics of BoAHV-1.1, BoGHV-4, and BVDV in bovine cell cultures: A proof-of-concept study.Virus research · 2025Article
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- Platelet activation stimulates macrophages to enhance ulcerative colitis through PF4/CXCR3 signaling.International journal of molecular medicine · 2025Article
- Understanding the pro- & anti-inflammatory cytokine profile in Japanese encephalitis & their implications in survival outcome.The Indian journal of medical research · 2025Article
- Platelet factor 4-derived C15 peptide broadly inhibits enteroviruses by disrupting viral attachment.Journal of virology · 2025Article
- Platelet Factor 4: A Mysterious Chemokine in Inflammatory Regulation Diseases.Journal of inflammation research · 2025Review
- Leukocyte recruitment in flavivirus-induced encephalitis.Frontiers in immunology · 2025Review
- Platelets in infection: intrinsic roles and functional outcomes.Frontiers in immunology · 2025Review
- Dengue virus: pathogenesis and potential for small molecule inhibitors.Bioscience reports · 2024Review
- Dynamics of platelet parameters in children with severe community-acquired pneumonia between viral and bacterial infections.Translational pediatrics · 2024Article
- Article
- Dabie bandavirus infection induces macrophagic pyroptosis and this process is attenuated by platelets.PLoS neglected tropical diseases · 2023Article
- Review
- The role of platelets in the blood-brain barrier during brain pathology.Frontiers in cellular neuroscience · 2023Review
- Chemokine PF4 Inhibits EV71 and CA16 Infections at the Entry Stage.Journal of virology · 2022Article
- Article
- Platelet-Released Factors: Their Role in Viral Disease and Applications for Extracellular Vesicle (EV) Therapy.International journal of molecular sciences · 2022Review
- Receptors for Respiratory Syncytial Virus Infection and Host Factors Regulating the Life Cycle of Respiratory Syncytial Virus.Frontiers in cellular and infection microbiology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivated platelets release cytokines/proteins including CXCL4 (PF4), CCL5 and fibrinopeptides, which regulate infection of several pathogenic viruses such as HIV, H1N1 and HCV in human. Since platelet activation is the hallmark of Dengue virus (DV) infection, we investigated the role of platelets in DV replication and also in a closely related Japanese Encephalitis virus (JEV). METHODS AND
findingsMicroscopy and PCR analysis revealed a 4-fold increase in DV replication in primary monocytes or monocytic THP-1 cells in vitro upon incubation with either DV-activated platelets or supernatant from DV-activated platelets. The mass spectrometry based proteomic data from extra-nuclear fraction of above THP-1 lysate showed the crucial association of PF4 with enhanced DV replication. Our cytokine analysis and immunoblot assay showed significant inhibition of IFN-α production in monocytes via p38MAPK-STAT2-IRF9 axis. Blocking PF4 through antibodies or its receptor CXCR3 through inhibitor i.e. AMG487, significantly rescued production of IFN-α resulting in potent inhibition of DV replication in monocytes. Further, flow cytometry and ELISA data showed the direct correlation between elevated plasma PF4 with increased viral NS1 in circulating monocytes in febrile DV patients at day-3 of fever than day-9. Similarly, PF4 also showed direct effects in promoting the JEV replication in monocytes and microglia cells in vitro. The in vitro results were also validated in mice, where AMG487 treatment significantly improved the survival of JEV infected animals.
interpretationOur study suggests that PF4-CXCR3-IFN axis is a potential target for developing treatment regimen against viral infections including JEV and DV.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.