ArticleBlood2019
Human megakaryocytes possess intrinsic antiviral immunity through regulated induction of IFITM3.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 184 citations in OpenAlex.
- Apoptosis-resistant megakaryocytes produce large and hyperreactive platelets in response to radiation injury.Military Medical Research · 2023Trial
- P2Y12-P-selectin-mediated platelet activation in a murine model of dengue-associated thrombocytopenia.EBioMedicine · 2026Article
- Megakaryocytes Internalize and Are Activated by Immune Complexes.Circulation research · 2026Article
- Immunomodulatory role of megakaryocytes in the hematopoietic niche of myeloproliferative neoplasms.Haematologica · 2026Article
- Beyond Hemostasis: Platelet Biomarkers and Vascular-Immune Crosstalk in Dengue.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Viral subversion of megakaryopoiesis: reshaping the landscapes of immune regulation.Infection · 2026Review
- Construction of a risk prediction model for multiple bronchoalveolar lavages in children with necrotizing pneumonia based on LASSO regression.Pediatric research · 2026Article
- Evaluating antiviral candidates for dengue virus infection: A review.Parasite epidemiology and control · 2026Review
- Clinical characteristics of thrombocytopenia in tropical diseases and management in resource-limited settings.Research and practice in thrombosis and haemostasis · 2026Review
- Megakaryocyte phenotyping in response to SARS-CoV-2 variants.Platelets · 2025Article
- Megakaryocytic Differentiation Regulates the Permissiveness and Antiviral Response of the Megakaryocytic Erythroid Progenitor to Dengue Virus.International journal of molecular sciences · 2025Article
- Single-Cell transcriptomic profiles of peripheral blood immune cells reveal early monocyte and platelet activation in the transition from high-risk states to clinical sepsis.Scientific reports · 2025Article
- Review
- Localized Inflammation in Dengue Vaccine-Induced Skin Rash Is Not Associated with Continuous Presence of Dengue Virus Genome.The Journal of investigative dermatology · 2025Article
- Periodontitis-induced neuroinflammation triggers IFITM3-Aβ axis to cause alzheimer's disease-like pathology and cognitive decline.Alzheimer's research & therapy · 2025Article
- Mature megakaryocytes acquire immune characteristics in a mouse model of aplastic anemia.Blood advances · 2025Article
- New insights into the generation and function of megakaryocytes in health and disease.Haematologica · 2025Review
- Elevated interferon-induced transmembrane protein 3 in platelets and megakaryocytes suppresses Crimean-Congo hemorrhagic fever viral infection by interacting with glycoprotein Gc.Virologica Sinica · 2025Article
- Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome.Acta biochimica et biophysica Sinica · 2025Article
- Adenovirus vectors can infect mouse megakaryocytes - implications for vaccine-induced thrombosis/thrombocytopenia.Research and practice in thrombosis and haemostasis · 2025Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 6 institutions in 3 countries.
Funding
Abstract
Evolving evidence indicates that platelets and megakaryocytes (MKs) have unexpected activities in inflammation and infection; whether viral infections upregulate biologically active, antiviral immune genes in platelets and MKs is unknown, however. We examined antiviral immune genes in these cells in dengue and influenza infections, viruses that are global public health threats. Using complementary biochemical, pharmacological, and genetic approaches, we examined the regulation and function of interferon-induced transmembrane protein 3 (IFITM3), an antiviral immune effector gene not previously studied in human platelets and MKs. IFITM3 was markedly upregulated in platelets isolated from patients during clinical influenza and dengue virus (DENV) infections. Lower IFITM3 expression in platelets correlated with increased illness severity and mortality in patients. Administering a live, attenuated DENV vaccine to healthy subjects significantly increased platelet IFITM3 expression. Infecting human MKs with DENV selectively increased type I interferons and IFITM3. Overexpression of IFITM3 in MKs was sufficient to prevent DENV infection. In naturally occurring, genetic loss-of-function studies, MKs from healthy subjects harboring a homozygous mutation in IFITM3 (rs12252-C, a common single-nucleotide polymorphism in areas of the world where DENV is endemic) were significantly more susceptible to DENV infection. DENV-induced MK secretion of interferons prevented infection of bystander MKs and hematopoietic stem cells. Thus, viral infections upregulate IFITM3 in human platelets and MKs, and IFITM3 expression is associated with adverse clinical outcomes. These observations establish, for the first time, that human MKs possess antiviral functions, preventing DENV infection of MKs and hematopoietic stem cells after local immune signaling.
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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.