自1990年代以来,北美地方性猪甲型流感病毒(swFLUAVs)含有一个内部基因片段星座,三重重排内部基因(TRIG)盒。2009年,H1N1大流行(pdmH1N1)病毒又蔓延到猪体内,但并未成为地方性流行。然而,pdmH1N1将基质基因(pdmM)贡献给猪群体中循环的swFLUAVs,它取代了TRIG盒中发现的经典猪基质基因(swM),表明pdmM具有健身益处。其他人已经表明,与含有swM基因区段的病毒相比,含有pdmM的swFLUAV具有更大的传播效率。我们假设矩阵(M)基因也可能影响疾病,并利用两个感染模型,抗性BALB/c和易感DBA/2小鼠,评估致病性。我们用含有swM或pdmM的H1和H3swFLUAVs感染BALB/c和DBA/2小鼠,并测量肺病毒滴度,发病率,死亡率,和肺组织病理学。含有pdmM基因的H1流感毒株在耐药和易感鼠株中引起更高的发病率和死亡率,而H3swFLUAVs没有引起临床疾病。然而,含有pdmM的H1和H3swFLUAVs在肺中都复制了更高的病毒滴度,与swMH1病毒相比,含有pdmM的H1病毒诱导了更大的组织学变化。虽然表面糖蛋白和其他基因片段可能有助于swFLUAV在小鼠中的致病性,这些数据表明,基质基因的起源也有助于swFLUAV在小鼠中的致病性,尽管我们在将这些结论转化为自然宿主时必须谨慎,猪。重要性2009年大流行的H1N1病毒迅速蔓延到北美猪,与已经遗传多样的swfluav进行重组。值得注意的是,M基因片段很快取代了经典的M基因片段,建议健身的好处。这里,使用两种小鼠感染模型,我们证明,与含有经典猪M基因的分离株相比,含有大流行H1N1起源M基因的swFLUAV分离株引起的疾病增加。这些结果表明,除了其他流感病毒基因片段,swFLUAVM基因片段有助于哺乳动物的发病机理。
Since the 1990s, endemic North American swine influenza A viruses (swFLUAVs) contained an internal gene segment constellation, the triple reassortment internal gene (TRIG) cassette. In 2009, the H1N1 pandemic (pdmH1N1) virus spilled back into swine but did not become endemic. However, the pdmH1N1 contributed the matrix gene (pdmM) to the swFLUAVs circulating in the pig population, which replaced the classical swine matrix gene (swM) found in the TRIG cassette, suggesting the pdmM has a fitness benefit. Others have shown that swFLUAVs containing the pdmM have greater transmission efficiency compared to viruses containing the swM gene segment. We hypothesized that the matrix (M) gene could also affect disease and utilized two infection models, resistant BALB/c and susceptible DBA/2 mice, to assess pathogenicity. We infected BALB/c and DBA/2 mice with H1 and H3 swFLUAVs containing the swM or pdmM and measured lung virus titers, morbidity, mortality, and lung histopathology. H1 influenza strains containing the pdmM gene caused greater morbidity and mortality in resistant and susceptible murine strains, while H3 swFLUAVs caused no clinical disease. However, both H1 and H3 swFLUAVs containing the pdmM replicated to higher viral titers in the lungs and pdmM containing H1 viruses induced greater histological changes compared to swM H1 viruses. While the surface glycoproteins and other gene segments may contribute to swFLUAV pathogenicity in mice, these data suggest that the origin of the matrix gene also contributes to pathogenicity of swFLUAV in mice, although we must be cautious in translating these conclusions to their natural host, swine.
OBJECTIVE: The 2009 pandemic H1N1 virus rapidly spilled back into North American swine, reassorting with the already genetically diverse swFLUAVs. Notably, the M gene segment quickly replaced the classical M gene segment, suggesting a fitness benefit. Here, using two murine models of infection, we demonstrate that swFLUAV isolates containing the pandemic H1N1 origin M gene caused increased disease compared to isolates containing the classical swine M gene. These results suggest that, in addition to other influenza virus gene segments, the swFLUAV M gene segment contributes to pathogenesis in mammals.