Baid Kaushal, Shrivastava Sauhard, Luc Jessica, Richard Daniel, Aguiar Jennifer A, Machado Yoan, Aicher Sophie-Marie, Siwak Kimberley C, LeBlanc Emmanuelle V, Khatooni Zahed, Lokugamage Kumari G, Vu Michelle N, Morgan Angelica, Bhuinya Arkadeb, Chiok Kim R, Nguyen Hai T, Stacey Hannah D, Scruten Erin, Prysliak Tracy, Yim Winfield, McArthur Andrew G, Miller Matthew S, Wilson Heather L, Capellini Terence, Faure Paul A, Liu Qiang, Mubareka Samira, Menachery Vineet D, Mossman Karen, Müller Marcel A, Drosten Christian, Colpitts Che C, Jouvenet Nolwenn, Overall Christopher M, Doxey Andrew C, Banerjee Arinjay
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada.
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Cell Rep. 2025 Jul 22;44(7):115929. doi: 10.1016/j.celrep.2025.115929. Epub 2025 Jul 1.
SARS-CoV-2 has caused the largest known coronavirus pandemic and is believed to have emerged from insectivorous bats. Little is known about the evolution of these viruses in their reservoir bat species. In this study, we investigate the SARS-CoV-2-host interaction using human and bat cells. Bat cells mount a robust and early antiviral response but elicit a dampened proinflammatory response upon SARS-CoV-2 infection compared to human cells. Furthermore, an inactivating R685P mutation within the furin cleavage site (FCS) of the SARS-CoV-2 spike protein is naturally selected for in infected bat cells. Taken together, our data demonstrate that insectivorous Eptesicus fuscus bat cells have evolved a differential antiviral immune response against SARS-CoV-2 infection, likely contributing to their disease tolerance ability. Our study sheds light on the evolution of sarbecoviruses in bats and extends molecular evidence to data from field studies that have demonstrated that SARS-CoV-2-related viruses in wild-caught bats lack an intact FCS.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引发了已知规模最大的冠状病毒大流行，据信它起源于食虫蝙蝠。对于这些病毒在其宿主蝙蝠物种中的进化情况，人们知之甚少。在本研究中，我们使用人类细胞和蝙蝠细胞来研究SARS-CoV-2与宿主的相互作用。与人类细胞相比，蝙蝠细胞会产生强烈且早期的抗病毒反应，但在感染SARS-CoV-2后引发的促炎反应会减弱。此外，在感染的蝙蝠细胞中，SARS-CoV-2刺突蛋白的弗林蛋白酶切割位点（FCS）内的失活R685P突变会被自然选择。综合来看，我们的数据表明，食虫棕蝠细胞已经进化出针对SARS-CoV-2感染的不同抗病毒免疫反应，这可能有助于它们的疾病耐受能力。我们的研究揭示了蝙蝠中沙贝病毒的进化，并将分子证据扩展到了野外研究的数据，这些数据表明，野生捕获蝙蝠中的SARS-CoV-2相关病毒缺乏完整的FCS。
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