Praneechit H.Thiemmeca S.Prayongkul D.Kongmanas K.Mairiang D.Punyadee N.Songjaeng A.Tangthawornchaikul N.Angkasekwinai N.Sriruksa K.Suputtamongkol Y.Limpitikul W.Atkinson J.P.Avirutnan P.Mahidol University2024-12-202024-12-202024-12-01mBio Vol.15 No.12 (2024)21612129https://repository.li.mahidol.ac.th/handle/20.500.14594/102448Dengue virus (DENV) infection poses a significant global health threat, yet our understanding of its immunopathogenesis remains incomplete due to limitations of existing models. Here, we establish an in vitro whole-blood model using hirudin, an anticoagulant that preserves complement activity and cellular interactions, to study DENV infection. Our model reveals the susceptibility of all major leukocyte populations to DENV infection, with monocytes and granulocytes demonstrating high permissiveness and production of infectious virus progeny. Notably, granulocytes emerge as previously unrecognized targets of DENV infection, highlighting the importance of studying viral tropism within a physiologically relevant context. We also observed efficient DENV binding to B cells, but limited production of infectious virus, suggesting a potential role in viral sequestration or immune dysregulation. Interestingly, both NK and T cells, while less permissive, were also found to be susceptible to DENV infection. Our ex vivo analysis of whole blood from DENV-infected patients confirms the susceptibility of granulocytes, monocytes, B cells, natural killer cells, and T cells to infection, further validating the clinical relevance of our model. Additionally, we observed dynamic changes in circulating blood cell populations during acute dengue, potentially reflecting both direct virus-mediated effects and immune responses. This whole-blood model offers a valuable tool for investigating the complex interplay between DENV and host factors, facilitating a deeper understanding of dengue pathogenesis and ultimately contributing to the development of novel therapeutic strategies.Immunology and MicrobiologyArticleSCOPUS10.1128/mbio.01505-242-s2.0-852119905182150751139540772