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时间依赖性促炎反应塑造了甲型流感病毒和乙型流感病毒共感染期间的病毒干扰。

Time-Dependent Proinflammatory Responses Shape Virus Interference during Coinfections of Influenza A Virus and Influenza D Virus.

机构信息

MU Center for Influenza and Emerging Infectious Diseases, University of Missouri, Columbia, MO 65211, USA.

Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65211, USA.

出版信息

Viruses. 2022 Jan 24;14(2):224. doi: 10.3390/v14020224.

Abstract

Both influenza A virus (IAV) and influenza D virus (IDV) are enzootic in pigs. IAV causes approximately 100% morbidity with low mortality, whereas IDV leads to only mild respiratory diseases in pigs. In this study, we performed a series of coinfection experiments in vitro and in vivo to understand how IAV and IDV interact and cause pathogenesis during coinfection. The results showed that IAV inhibited IDV replication when infecting swine tracheal epithelial cells (STECs) with IAV 24 or 48 h prior to IDV inoculation and that IDV suppressed IAV replication when IDV preceded IAV inoculation by 48 h. Virus interference was not identified during simultaneous IAV/IDV infections or with 6 h between the two viral infections, regardless of their order. The interference pattern at 24 and 48 h correlated with proinflammatory responses induced by the first infection, which, for IDV, was slower than for IAV by about 24 h. The viruses did not interfere with each other if both infected the cells before proinflammatory responses were induced. Coinfection in pigs further demonstrated that IAV interfered with both viral shedding and virus replication of IDV, especially in the upper respiratory tract. Clinically, coinfection of IDV and IAV did not show significant enhancement of disease pathogenesis, compared with the pigs infected with IAV alone. In summary, this study suggests that interference during coinfection of IAV and IDV is primarily due to the proinflammatory response; therefore, it is dependent on the time between infections and the order of infection. This study facilitates our understanding of virus epidemiology and pathogenesis associated with IAV and IDV coinfection.

摘要

甲型流感病毒(IAV)和乙型流感病毒(IDV)在猪中均为地方流行病毒。IAV 会导致约 100%的猪发病,但死亡率低,而 IDV 只会导致猪发生轻微的呼吸道疾病。在本研究中,我们进行了一系列的体外和体内共感染实验,以了解 IAV 和 IDV 在共感染时如何相互作用并引起发病机制。结果表明,IAV 在感染猪气管上皮细胞(STEC)时,先于 IDV 接种 24 或 48 小时,可以抑制 IDV 的复制,而 IDV 先于 IAV 接种 48 小时,可以抑制 IAV 的复制。无论是先接种 IAV 还是 IDV,同时感染 IAV/IDV 或两种病毒感染之间间隔 6 小时,都没有发现病毒干扰。24 小时和 48 小时的干扰模式与第一次感染诱导的促炎反应有关,对于 IDV 来说,大约比 IAV 慢 24 小时。如果两种病毒在诱导促炎反应之前都感染细胞,则它们不会相互干扰。在猪中的共感染进一步表明,IAV 干扰了 IDV 的病毒脱落和复制,尤其是在上呼吸道。临床上,与单独感染 IAV 的猪相比,IDV 和 IAV 的共感染并没有明显加重疾病的发病机制。综上所述,本研究表明,IAV 和 IDV 共感染时的干扰主要是由于促炎反应引起的,因此,它取决于感染之间的时间和感染的顺序。本研究有助于我们理解与 IAV 和 IDV 共感染相关的病毒流行病学和发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d05/8878573/db2e661dea59/viruses-14-00224-g001.jpg

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