Adenovirus vectors can infect mouse megakaryocytes - implications for vaccine-induced thrombosis/thrombocytopenia

Collett, S; Earnest, L; Edeling, MA; Yap, AHY; Carrera Montoya, J; Attard, C; Di Rago, L; Farley, A; Ng, AP; Monagle, P; Torresi, J

Author(s): Collett, S; Earnest, L; Edeling, MA; Yap, AHY; Carrera Montoya, J; Attard, C; Di Rago, L; Farley, A; Ng, AP; Monagle, P; Torresi, J;
Details: Publication Year 2025-05,Volume 9,Issue #4,Page e102909
Journal Title: Research and Practice in Thrombosis and Haemostasis
Publication Type: Research article
Abstract: BACKGROUND: Adenoviruses, adenoviral vector vaccines, and gene delivery systems have been implicated in thrombosis/thrombocytopenia syndrome. The underlying cause remains unknown. We have previously hypothesized that infection of megakaryocytes (MKs), the progenitor cells of platelets, plays a central role in adenovirus- or adenoviral vector-induced thrombosis/thrombocytopenia. Further, recent work has highlighted that the MK population comprises multiple subsets, including cells with immune function, and we propose that this MK subset is involved in adenoviral infection and the subsequent response. OBJECTIVES: To determine whether MKs are permissive to infection by recombinant adenovirus encoding the SARS-CoV-2 spike protein, and whether infection is associated with phenotypic changes. METHODS: In this work, we generated adenovirus vectors based on the adenovirus 5 strain, with a green fluorescence protein reporter gene and encoding or not the SARS-CoV-2 Spike protein. Megakaryoblastic cell lines and MKs derived from mouse bone marrow and differentiated with thrombopoietin were exposed to adenoviral vectors, and infection was analyzed using flow cytometry and fluorescence microscopy. RESULTS: The primary finding of this study is that MKs were permissive to infection by recombinant adenoviruses carrying the Spike gene of ß-SARS-CoV-2, with higher rates of infection in mature MKs. Furthermore, the effect of adenoviral infection on the cell surface proteins CD41, CD42, and CXCR4 was investigated. Cell cultures stimulated with bacterial lipopolysaccharide, with and without concurrent adenoviral infection, demonstrated that lipopolysaccharide stimulation and adenoviral infection at moderate multiplicity of infection drove increased surface expression of the α chemokine receptor CXCR4, whereas adenoviral infection at a high multiplicity of infection reduced CXCR4 expression. CONCLUSION: We found that adenoviral infection was higher in higher-ploidy CD41(+)CD42(+) and CXCR4(hi) MKs, implicating these receptors in the MK response to adenoviral infection.
Publisher: Elsevier
Keywords: Adenoviridae; hemostasis; megakaryocyte; thrombocytopenia; thrombosis
Department(s): Haematology
Publisher's Version: https://doi.org/10.1016/j.rpth.2025.102909
Open Access at Publisher's Site: https://doi.org/10.1016/j.rpth.2025.102909
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-07-22 06:23:44

Last Modified: 2025-07-22 06:25:04