Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, 27710, USA.
Department of Microbiology and Immunology, Center for Immunology University of Minnesota, Minneapolis, MN, 55455, USA.
Nat Commun. 2019 Feb 15;10(1):779. doi: 10.1038/s41467-019-08617-z.
Influenza B virus (IBV) is an acute, respiratory RNA virus that has been assumed to induce the eventual death of all infected cells. We and others have shown however, that infection with apparently cytopathic viruses does not necessarily lead to cell death; some cells can intrinsically clear the virus and persist in the host long-term. To determine if any cells can survive direct IBV infection, we here generate a recombinant IBV capable of activating a host-cell reporter to permanently label all infected cells. Using this system, we demonstrate that IBV infection leads to the formation of a survivor cell population in the proximal airways that are ciliated-like, but transcriptionally and phenotypically distinct from both actively infected and bystander ciliated cells. We also show that survivor cells are critical to maintain respiratory barrier function. These results highlight a host response pathway that preserves the epithelium to limit the severity of IBV disease.
乙型流感病毒（IBV）是一种急性呼吸道 RNA 病毒，据推测会导致所有感染细胞最终死亡。然而，我们和其他人已经表明，感染明显具有细胞病变的病毒并不一定会导致细胞死亡；一些细胞可以内在清除病毒并在宿主中长期存在。为了确定是否有任何细胞可以在直接 IBV 感染后存活，我们在此生成了一种能够激活宿主细胞报告基因的重组 IBV，以永久标记所有感染的细胞。使用该系统，我们证明 IBV 感染会导致近端气道中形成一个类似于纤毛的存活细胞群体，但在转录和表型上与活跃感染和旁观者纤毛细胞都不同。我们还表明，存活细胞对于维持呼吸屏障功能至关重要。这些结果突出了一种宿主反应途径，该途径可以保护上皮细胞，从而限制 IBV 疾病的严重程度。
