Although numerous studies have clarified the synergistic pathogenesis in mouse models of influenza A virus (IAV)-associated dual infections, fewer studies have investigated the influence of intranasal liquid administration on the disease. This study explored the effects of intranasal PBS administration in mouse models of mimic IAV dual infection and the infectious dose of IAV that caused equivalent pathogenesis in different dual infection models. Weights, survival rates, virus loads, lung indexes and lung pathology were compared. We demonstrated that intranasal PBS administration following H1N1 or H3N2 infection increased weight loss, mortality, virus replication and lung damage. No difference was observed if the order was reversed or PBS was given simultaneously with IAV. To induce equivalent virulence, a 20-fold difference in the infectious dose was needed when the H3N2–PBS superinfection and H3N2–PBS coinfection or PBS–H3N2 superinfection groups were compared. Our study demonstrated that the unfavourable effect of intranasal liquid administration should not be neglected and that both the strain and infectious dose of IAV should be considered to avoid an illusion of synergistic pathogenicity when establishing IAV-associated dual infection model. A 20-fold lower dose than that of coinfection may be a better choice for secondary infection following IAV.

中文翻译：

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在小鼠中感染流感病毒后，通过鼻腔内液体给药加剧疾病。

尽管许多研究已经阐明了与A型流感病毒（IAV）相关的双重感染的小鼠模型中的协同发病机理，但很少有研究研究了鼻内给药对疾病的影响。这项研究探讨了在模拟IAV双重感染的小鼠模型中鼻腔内PBS给药的效果以及在不同的双重感染模型中引起等效发病机理的IAV的感染剂量。比较体重，存活率，病毒载量，肺指数和肺病理。我们证明，H1N1或H3N2感染后鼻内PBS给药会增加体重减轻，死亡率，病毒复制和肺损伤。如果顺序相反或与IAV同时给予PBS，则没有观察到差异。为了诱发同等毒力，当比较H3N2-PBS重叠感染和H3N2-PBS合并感染或PBS-H3N2重叠感染组时，感染剂量需要相差20倍。我们的研究表明，鼻内液体给药的不利影响不容忽视，建立IAV相关的双重感染模型时，应同时考虑IAV的毒株和感染剂量，以避免产生协同致病性的假象。比合并感染低20倍的剂量可能是IAV继发感染的更好选择。我们的研究表明，鼻内液体给药的不利影响不容忽视，建立IAV相关的双重感染模型时，应同时考虑IAV的毒株和感染剂量，以避免产生协同致病性的假象。比合并感染低20倍的剂量可能是IAV继发感染的更好选择。我们的研究表明，鼻内输液的不利影响不容忽视，建立IAV相关双重感染模型时，应同时考虑IAV的毒株和感染剂量，以避免产生协同致病性的假象。比合并感染低20倍的剂量可能是IAV继发感染的更好选择。