Gonzalez Victoria, Word Cierra, Guerra-Pilaquinga Nahomi, Mazinani Mitra, Fawcett Stephen, Portfors Christine, Falzarano Darryl, Kell Alison M, Jangra Rohit K, Banerjee Arinjay, Seifert Stephanie N, Letko Michael
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Canada.
Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, Canada.
PLoS Biol. 2025 Apr 15;23(4):e3003098. doi: 10.1371/journal.pbio.3003098. eCollection 2025 Apr.
Multiple viruses that are highly pathogenic in humans are known to have evolved in bats. How bats tolerate infection with these viruses, however, is poorly understood. As viruses engage in a wide range of interactions with their hosts, it is essential to study bat viruses in a system that resembles their natural environment like bat-derived in vitro cellular models. However, stable and accessible bat cell lines are not widely available for the broader scientific community. Here, we generated in vitro reagents for the Seba's short-tailed bat (Carollia perspicillata), tested multiple methods of immortalization, and characterized their susceptibility to virus infection and response to immune stimulation. Using pseudotyped virus library and authentic virus infections, we show that these C. perspicillata cell lines derived from a diverse array of tissues are susceptible to viruses bearing the glycoprotein of numerous orthohantaviruses, including Andes and Hantaan virus and are also susceptible to live hantavirus infection. Furthermore, stimulation with synthetic double-stranded RNA prior to infection with vesicular stomatitis virus and Middle Eastern respiratory syndrome coronavirus induced a protective antiviral response, demonstrating the suitability of our cell lines to study the bat antiviral immune response. Taken together, the approaches outlined here will inform future efforts to develop in vitro tools for virology from non-model organisms and these C. perspicillata cell lines will enable studies on virus-host interactions in these bats.
已知多种对人类具有高致病性的病毒是在蝙蝠体内进化而来的。然而，蝙蝠如何耐受这些病毒的感染却鲜为人知。由于病毒与其宿主之间存在广泛的相互作用，因此在类似于其天然环境的系统（如源自蝙蝠的体外细胞模型）中研究蝙蝠病毒至关重要。然而，稳定且易于获取的蝙蝠细胞系并未广泛提供给更广泛的科学界。在这里，我们为白氏短尾蝠（Carollia perspicillata）生成了体外试剂，测试了多种永生化方法，并表征了它们对病毒感染的易感性以及对免疫刺激的反应。使用假型病毒库和真实病毒感染，我们表明这些源自多种组织的白氏短尾蝠细胞系对携带多种正汉坦病毒糖蛋白的病毒敏感，包括安第斯病毒和汉滩病毒，并且也易受活汉坦病毒感染。此外，在用水疱性口炎病毒和中东呼吸综合征冠状病毒感染之前用合成双链RNA刺激可诱导保护性抗病毒反应，这表明我们的细胞系适合研究蝙蝠抗病毒免疫反应。综上所述，本文概述的方法将为未来开发非模式生物病毒学体外工具的努力提供信息，并且这些白氏短尾蝠细胞系将有助于研究这些蝙蝠中的病毒-宿主相互作用。
