Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands.
PLoS One. 2012;7(8):e42343. doi: 10.1371/journal.pone.0042343. Epub 2012 Aug 8.
Humans may be infected by different influenza A viruses--seasonal, pandemic, and zoonotic--which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues--including the central nervous system--for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets.
人类可能会感染不同的甲型流感病毒——季节性、大流行和人畜共患病——这些病毒的表现从轻度上呼吸道疾病到严重且有时致命的肺炎伴呼吸道外播散有所不同。这些感染在时空动态方面的差异尚未得到充分理解。因此，我们用季节性 H3N2、大流行 H1N1（pH1N1）和高致病性禽流感 H5N1 流感病毒感染雪貂，并在接种后 0.5 至 14 天（dpi）的时间点进行了详细的病毒学和病理学分析，同时还描述了临床症状和血液学参数。H3N2 感染局限于鼻腔，在 1dpi 时达到高峰。pH1N1 感染也在 1dpi 时达到高峰，但在整个呼吸道中水平相似。H5N1 感染主要发生在肺泡中，其高峰期持续时间更长，为 1 至 3dpi。相关病变的空间分布与病毒感染相同，但在 1 至 6 天后达到严重程度的峰值。外周血中性粒细胞和单核细胞计数与肺泡中炎症细胞的涌入相关。在用于测量下呼吸道疾病的不同参数中，相对肺重和受影响的肺组织允许在病毒组之间进行最佳的定量区分。与 pH1N1 感染相比，H5N1 感染向更多组织（包括中枢神经系统）发生了呼吸道外播散，而 H3N2 感染则没有。这项研究表明，季节性、大流行和人畜共患病流感病毒在雪貂呼吸道和呼吸道外组织中的感染时空动态方面存在很大差异。
