Schwab Lara S U, Do Thi H T, Pilapitiya Devaki, Koutsakos Marios
Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
J Virol. 2024 Jun 13;98(6):e0160423. doi: 10.1128/jvi.01604-23. Epub 2024 May 23.
The global burden of disease caused by influenza B virus (IBV) is substantial; however, IBVs remain overlooked. Understanding host-pathogen interactions and establishing physiologically relevant models of infection are important for the development and assessment of therapeutics and vaccines against IBV. In this study, we assessed an upper respiratory tract (URT)-restricted model of mouse IBV infection, comparing it to the conventional administration of the virus to the total respiratory tract (TRT). We found that URT infections caused by different strains of IBV disseminate to the trachea but resulted in limited dissemination of IBV to the lungs. Infection of the URT did not result in weight loss or systemic inflammation even at high inoculum doses and despite robust viral replication in the nose. Dissemination of IBV to the lungs was enhanced in mice lacking functional type I IFN receptor (IFNAR2), but not IFNγ. Conversely, in mice expressing the IFN-inducible gene Mx1, we found reduced IBV replication in the lungs and reduced dissemination of IBV from the URT to the lungs. Inoculation of IBV in both the URT and TRT resulted in seroconversion against IBV. However, priming at the TRT conferred superior protection from a heterologous lethal IBV challenge compared to URT priming, as determined by improved survival rates and reduced viral replication throughout the respiratory tract. Overall, our study establishes a URT-restricted IBV infection model, highlights the critical role of IFNs in limiting dissemination of IBV to the lungs, and also demonstrates that the lack of viral replication in the lungs may impact protection from subsequent infections.
Our study investigated how influenza B virus (IBV) spreads from the nose to the lungs of mice and the impact this has on disease and protection from re-infection. We found that when applied to the nose only, IBV does not spread very efficiently to the lungs in a process controlled by the interferon response. Priming immunity at the nose only resulted in less protection from re-infection than priming immunity at both the nose and lungs. These insights can guide the development of potential therapies targeting the interferon response as well as of intranasal vaccines against IBV.
乙型流感病毒（IBV）造成的全球疾病负担相当大；然而，IBV仍然被忽视。了解宿主与病原体的相互作用并建立生理相关的感染模型对于开发和评估针对IBV的治疗方法和疫苗很重要。在本研究中，我们评估了小鼠IBV感染的上呼吸道（URT）受限模型，并将其与病毒常规接种至整个呼吸道（TRT）的情况进行比较。我们发现，由不同株IBV引起的URT感染会扩散至气管，但IBV扩散至肺部的程度有限。即使在高接种剂量下，且尽管鼻腔中有强劲的病毒复制，URT感染也不会导致体重减轻或全身炎症。在缺乏功能性I型干扰素受体（IFNAR2）而非IFNγ的小鼠中，IBV向肺部的扩散增强。相反，在表达干扰素诱导基因Mx1的小鼠中，我们发现肺部的IBV复制减少，且IBV从URT向肺部的扩散减少。在URT和TRT中接种IBV均导致针对IBV的血清转化。然而，如通过提高生存率和减少整个呼吸道中的病毒复制所确定的，与URT启动相比，TRT启动对异源致死性IBV攻击具有更好的保护作用。总体而言，我们的研究建立了一种URT受限的IBV感染模型，突出了干扰素在限制IBV扩散至肺部方面的关键作用，并且还证明肺部缺乏病毒复制可能会影响对后续感染的保护。
我们的研究调查了乙型流感病毒（IBV）如何从小鼠的鼻子传播至肺部，以及这对疾病和预防再次感染的影响。我们发现，仅应用于鼻子时，IBV在由干扰素反应控制的过程中向肺部的传播效率不高。仅在鼻子启动免疫所提供的对再次感染的保护比在鼻子和肺部同时启动免疫要少。这些见解可以指导针对干扰素反应的潜在治疗方法以及针对IBV的鼻内疫苗的开发。
