Alveolar macrophages are early targets of mumps virus 2177

Abstract Description Mumps virus (MuV) remains active worldwide, despite high vaccine coverage. MuV is thought to infect the upper respiratory tract before disseminating to other organs; however, the early cellular targets of MuV in vivo are unknown. We generated a GFP-tagged vaccine strain (JL5) of MuV to infect leukocytic cell lines and found that replication was greatest in monocytes. Infection of PBMCs also showed that both JL5 and a circulating strain of MuV (Iowa 2006; genotype G), preferentially infected monocytes. Monocyte-derived macrophages showed high susceptibility to MuV, with genotype G infecting macrophages to a greater extent. While mice are generally resistant to MuV infection, we inoculated immunocompetent Rosa26-tdTomato mice intranasally with a GFP and Cre recombinase tagged MuV to determine whether monocytes/macrophages are important targets in vivo. We observed a small population of tdtomato+ cells within the lungs and found they were primarily alveolar macrophages (AMs). We validated these findings by infecting murine AMs isolated from Rosa26-tdTomato mice with MuV. While MuV could enter AMs (tdTomato+), only a small subset expressed GFP, suggesting that inhibition in murine cells occurs post-entry. We then isolated cells from human bronchioalveolar lavage fluid and infected them with MuV ex vivo, finding the majority of GFP+ cells were AMs. These findings highlight the high susceptibility of AMs and provide a basis for early MuV pathogenesis and subsequent dissemination. Funding Sources Supported by: U19AI171403, PR192188, R01AI188431, T32GM146636 Topic Categories Viral Immunology (VIR)