Major Disruption of Bone Marrow Stromal Cell Networks and Persistent Loss of Hematopoietic Stem Cell Function upon Chronic Viral Infection

Finely tuned, demand adapted hematopoiesis relies on the exchange of complex regulatory signals between hematopoietic and stromal cells of the bone marrow (BM) microenvironment. For instance, hematopoietic stem and progenitor cells (HSPCs) are maintained by mesenchymal, vascular and neural cells in defined BM niches. Viral infections and ensuing inflammatory responses are known to induce massive changes in the hematopoietic output. Nonetheless, little is known about the alterations elicited on the composition, structure and function of BM stromal cells and their regulatory crosstalk with HSCs after chronic viral challenge. We used a combination of conventional in vitro and in vivo assays, RNA-seq and 3D confocal quantitative imaging to address these questions in a model of chronic Lymphocytic Choriomeningitis Virus (LCMV) infection.