Perturbation of bone marrow microniche as mechanism of measles virus-induced long-term immune memory loss 9161

Abstract Description Measles-associated deaths are primarily attributed to secondary infections that can arise due to immunosuppression such as loss of pre-existing antibody repertoires. Yet the determinants of this humoral immunosuppression are not fully understood. This study explored the impact of measles virus (MeV) infection on the bone marrow (BM), a major reservoir for long-lived plasma cells. Infection of rhesus macaques with WT MeV (n = 3) or live-attenuated measles vaccine (LAMV; n = 3) led to the detection of live WT MeV but not LAMV in peripheral blood and BM aspirates during acute infection. Bone marrow-derived mesenchymal stromal cells (BM-MSCs), which are crucial support cells for immune memory cells in the BM, were also isolated from MeV-naïve rhesus macaques and subjected to ex-vivo infections. BM-MSCs were susceptible to infection with both WT MeV and LAMV that induced significant cytotoxicity and reduced adhesion to BM mononuclear cells. Proteomic approaches using LC-MS revealed that WT MeV and LAMV infections commonly downregulated extracellular matrix proteins, such as collagen, fibronectin and heparin sulfate proteoglycans which implied both viruses could disrupt the bone marrow microniche. Our data suggests that MeV may alter the BM environment through direct infection, thereby contributing to the long-term loss of immune cell memory. While LAMV can infect BM cells ex-vivo, the virus does not reach the BM in-vivo and has no opportunity to affect it. Funding Sources NIH AI153140, AI182066, and JHSPH Frederick B. Bang Award Topic Categories Viral Immunology (VIR)