Mx1 in Hematopoietic Cells Protects against Thogoto Virus Infection

This study examined the contribution of the interferon-induced restriction factor Mx1 in hematopoietic versus nonhematopoietic compartments during viral infection, with a particular focus on Thogoto virus (THOV). Using reciprocal bone marrow chimera mice carrying functional or nonfunctional Mx1 alleles, the authors compared outcomes following infection with influenza A virus (IAV) and THOV. While resistance to IAV infection depended exclusively on Mx1 expression in nonhematopoietic (stromal) cells, THOV infection revealed a distinct requirement for Mx1 in bone marrow-derived cells. Mice lacking stromal Mx1 but reconstituted with Mx1-competent bone marrow showed delayed morbidity, reduced liver pathology, and significantly lower viral dissemination to spleen, lung, and serum compared with mice receiving Mx1-deficient bone marrow. Histopathology, serum ALT/AST measurements, viral titration, and immunohistochemical analyses demonstrated that Mx1 expression in CD45⁺ hematopoietic cells, likely myeloid cells, restricted THOV replication and delayed liver necrosis, although it did not fully prevent hepatic infection in the absence of stromal Mx1. Collectively, the results establish that, unlike influenza A virus, effective control of THOV infection critically involves Mx1 expression in hematopoietic cells, highlighting virus- and cell type–specific roles of intrinsic antiviral immunity.
(TMR)