Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, AL, 36688, USA.
Center for Lung Biology, College of Medicine, University of South Alabama, Mobile, AL, 36688, USA.
Sci Rep. 2022 Feb 24;12(1):3152. doi: 10.1038/s41598-022-06667-w.
Despite the availability of vaccines and antiviral therapies, seasonal influenza infections cause 400,000 human deaths on average per year. Low vaccine coverage and the occurrence of drug-resistant viral strains highlight the need for new and improved countermeasures. While influenza A virus (IAV) engineered to express a reporter gene may serve as a valuable tool for real-time tracking of viral infection, reporter gene insertion into IAV typically attenuates viral pathogenicity, hindering its application to research. Here, we demonstrate that lethal or even sublethal doses of bioluminescent IAV carrying the NanoLuc gene in the C-terminus of PB2 can be tracked in real-time in live mice without compromising pathogenicity. Real-time tracking of this bioluminescent IAV enables spatiotemporal viral replication tracking in animals that will facilitate the development of countermeasures by enhancing the interpretation of clinical signs and prognosis while also allowing less animal usage.
尽管有疫苗和抗病毒疗法可用，但季节性流感感染平均每年导致 40 万人死亡。疫苗接种率低和耐药病毒株的出现突出表明需要新的和改进的对策。虽然表达报告基因的工程改造流感病毒 (IAV) 可作为实时跟踪病毒感染的有价值工具，但报告基因插入 IAV 通常会削弱病毒的致病性，从而阻碍其在研究中的应用。在这里，我们证明，带有 NanoLuc 基因的生物发光 IAV 的致死甚至亚致死剂量可以在不影响致病性的情况下实时追踪活小鼠中的感染。这种生物发光 IAV 的实时追踪可以在动物中进行时空病毒复制追踪，这将通过增强对临床症状和预后的解释来促进对策的制定，同时也允许减少动物使用。
