Megakaryocytic Differentiation Regulates the Permissiveness and Antiviral Response of the Megakaryocytic Erythroid Progenitor to Dengue Virus

Dengue virus (DENV) affects not only peripheral immune cells but also hematopoietic progenitors in the bone marrow, particularly megakaryocytic precursors, which contribute to the thrombocytopenia characteristic of the disease. In this study, we evaluated the relationship between the differentiation status of the megakaryocytic lineage and its permissiveness and antiviral response to DENV. Our results demonstrate that the erythroid–megakaryocytic precursor (K562 cells) was more permissive to DENV infection than megakaryoblasts, as evidenced by immunofluorescence, flow cytometry, and quantification of viral particles. The antiviral response in K562 cells peaked at three days post-infection, with maximal expression of genes associated with the type I interferon (IFN-I) pathway. In vitro-induced differentiation of K562 cells reduced the initial susceptibility to DENV and enhanced the expression of Toll-like receptor 3 (TLR3) and the type I interferon receptor (IFNAR1), accelerating and intensifying IFN-β secretion, and increasing the expression of OAS2 and IRF3. Furthermore, pretreatment of K562 cells with recombinant IFN-β significantly reduced viral replication from the first day post-infection. Collectively, these findings demonstrate for the first time that the differentiation status of erythroid–megakaryocytic progenitor critically shapes their antiviral response and underscore the central role of IFN-β in the early restriction of DENV infection.

• Publication year

  2025

• Venue

  International Journal of Molecular Sciences

• Publication date

  2025-11-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/ijms262211081PMID 41303574PMCID 12652983
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Population at risk of dengue virus transmission has increased due to coupled climate factors and population growth

  2024cited by this paper
• Renaming of the genus Flavivirus to Orthoflavivirus and extension of binomial species names within the family Flaviviridae

  2023cited by this paper
• Dengue and Zika virus differential infection of human megakaryoblast MEG-01 reveals unique cellular markers.

  2022cited by this paper
• Influenza A virus infection instructs hematopoiesis to megakaryocyte-lineage output.

  2022cited by this paper
• Replication of Dengue Virus in K562-Megakaryocytes Induces Suppression in the Accumulation of Reactive Oxygen Species

  2022influential reference
• Global burden for dengue and the evolving pattern in the past 30 years.

  2021cited by this paper
• Dengue virus induces Interferon-β by activating RNA sensing pathways in megakaryocytes.

  2021influential reference
• Dengue virus infection impedes megakaryopoiesis in MEG-01 cells where the virus envelope protein interacts with the transcription factor TAL-1

  2020cited by this paper
• Megakaryopoiesis.

  2020cited by this paper
• TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons.

  2020cited by this paper
• Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells

  2019cited by this paper
• Dengue viruses infect human megakaryocytes, with probable clinical consequences

  2019cited by this paper
• Human megakaryocytes possess intrinsic antiviral immunity through regulated induction of IFITM3.

  2019cited by this paper
• Characterization of dengue virus 2 growth in megakaryocyte-erythrocyte progenitor cells.

  2016influential reference
• Dengue infection

  2016cited by this paper
• Antibody-dependent enhancement of dengue virus infection inhibits RLR-mediated Type-I IFN-independent signalling through upregulation of cellular autophagy

  2016cited by this paper
• Dengue Virus NS Proteins Inhibit RIG-I/MAVS Signaling by Blocking TBK1/IRF3 Phosphorylation: Dengue Virus Serotype 1 NS4A Is a Unique Interferon-Regulating Virulence Determinant

  2015cited by this paper
• Dengue Virus Control of Type I IFN Responses: A History of Manipulation and Control

  2015cited by this paper
• Expression and functionality of Toll‐like receptor 3 in the megakaryocytic lineage

  2015cited by this paper
• Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC‐SIGN and caspases

  2013cited by this paper
• The importance of hematopoietic progenitor cells in dengue

  2012cited by this paper
• Multiploid CD61+ Cells Are the Pre-Dominant Cell Lineage Infected during Acute Dengue Virus Infection in Bone Marrow

  2012cited by this paper
• Expression and functionality of type I interferon receptor in the megakaryocytic lineage

  2011cited by this paper
• The Oligoadenylate Synthetase Family: An Ancient Protein Family with Multiple Antiviral Activities

  2011cited by this paper
• Poly(I:C) Enhances the Susceptibility of Leukemic Cells to NK Cell Cytotoxicity and Phagocytosis by DC

  2011cited by this paper
• USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon α Response

  2011cited by this paper
• RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection

  2011cited by this paper
• Dengue 2 virus inhibits in vitro megakaryocytic colony formation and induces apoptosis in thrombopoietin-inducible megakaryocytic differentiation from cord blood CD34+ cells.

  2008cited by this paper
• Distinct RIG-I and MDA5 Signaling by RNA Viruses in Innate Immunity

  2007cited by this paper
• IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors

  2006cited by this paper
• Dengue-2 virus infection of human mononuclear cell lines and establishment of persistent infections

  2005cited by this paper
• Infection of Human Cells by Dengue Virus Is Modulated by Different Cell Types and Viral Strains

  2000cited by this paper
• Modulation of Dengue Virus Infection in Human Cells by Alpha, Beta, and Gamma Interferons

  2000cited by this paper
• Dengue virus, a flavivirus, propagates in human bone marrow progenitors and hematopoietic cell lines [see comments]

  1989cited by this paper
• Dengue virus, a flavivirus, propagates in human bone marrow progenitors and hematopoietic cell lines.

  1989cited by this paper
• DENGUE FEVER: A THROMBOCYTOPENIC DISEASE?

  1964cited by this paper

• No citing papers are available for this paper.