Compared with other mammals, bats harbor more zoonotic viruses per species and do not demonstrate signs of disease on infection with these viruses. To counteract infections with viruses, bats have evolved enhanced mechanisms to limit virus replication and immunopathology. However, molecular and cellular drivers of antiviral responses in bats largely remain an enigma. In this study, we demonstrate that a serine residue in IRF3 is positively selected for in multiple bat species. IRF3 is a central regulator of innate antiviral responses in mammals. Replacing the serine residue in bat IRF3 with the human leucine residue decreased antiviral protection in bat cells, whereas the addition of this serine residue in human IRF3 significantly enhanced antiviral protection in human cells. Our study provides genetic and functional evidence for enhanced IRF3-mediated antiviral responses in bats and adds support to speculations that bats have positively selected for multiple adaptations in their antiviral immune responses.

与其他哺乳动物相比，蝙蝠在每个物种中携带更多的人畜共患病毒，并且在感染这些病毒时不会表现出疾病迹象。为了抵抗病毒感染，蝙蝠进化出了增强的机制来限制病毒复制和免疫病理学。然而，蝙蝠抗病毒反应的分子和细胞驱动因素在很大程度上仍然是个谜。在这项研究中，我们证明 IRF3 中的丝氨酸残基在多个蝙蝠物种中被正向选择。 IRF3 是哺乳动物先天抗病毒反应的中心调节因子。用人亮氨酸残基替换蝙蝠IRF3中的丝氨酸残基会降低蝙蝠细胞中的抗病毒保护作用，而在人IRF3中添加该丝氨酸残基则显着增强了人细胞中的抗病毒保护作用。我们的研究为蝙蝠中 IRF3 介导的抗病毒反应增强提供了遗传和功能证据，并为蝙蝠在其抗病毒免疫反应中积极选择多种适应的推测提供了支持。