Toledo-Teixeira 2020

Oropouche orthobunyavirus (OROV) is an insect-transmitted bunyavirus that causes neurological disease in humans and is at high risk for emergence beyond its historical borders in Brazil. The pathogenic determinants associated with neurological involvement and pathogenesis of OROV are not fully understood. We demonstrate that B cells, but not T cells, control viral replication and dissemination to the central nervous system. Consistent with a protective role of B cells, wild-type (WT) mice efficiently produce antibodies within six days of infection, and transfer of serum antibodies containing IgM to Rag1–/– mice lacking B and T cells can prevent neurological disease. CD19-Cre+ MyD88fl mice are vulnerable and produce less and lower avidity IgM and IgG, and diminished OROV-neutralizing antibody responses than WT and Cre– MyD88fl mice. These results suggest that early MyD88-dependent immune responses in B cells are essential for generating adaptive responses that restrict OROV replication and prevent neurological disease in mice.