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.奥罗普切正布尼亚病毒（Oropouche orthobunyavirus, OROV）是一种经昆虫传播的布尼亚病毒（bunyavirus），可引发人类神经系统疾病，且存在突破巴西既往流行范围、实现跨境传播的高风险。目前，与该病毒引发神经系统受累及致病机制相关的致病决定因素尚未完全阐明。本研究证实，B细胞（B cell）而非T细胞（T cell）可调控病毒复制，并抑制其向中枢神经系统（central nervous system, CNS）的播散。与B细胞的保护性作用相符，野生型（wild-type, WT）小鼠在感染后6天内即可高效产生抗体；将含有免疫球蛋白M（Immunoglobulin M, IgM）的血清抗体转移至缺乏B、T细胞的Rag1–/–小鼠体内，可有效预防其发生神经系统疾病。相较于WT小鼠与Cre– MyD88fl小鼠，CD19-Cre+ MyD88fl小鼠更易感染该病毒，其产生的IgM、免疫球蛋白G（Immunoglobulin G, IgG）滴度更低、亲和力更弱，且中和奥罗普切正布尼亚病毒的抗体应答水平显著减弱。上述结果表明，B细胞中早期MyD88依赖性免疫应答，对于生成可限制奥罗普切正布尼亚病毒复制、并预防小鼠罹患神经系统疾病的适应性免疫应答至关重要。