comparison of temporal and spatial dynamics of seasonal h3n2, pandemic h1n1 and highly pathogenic avian influenza h5n1 virus infections in ferrets比较的时空动力学季节性h3n2,h1n1大流行性流感和高致病性禽流感h5n1病毒感染雪貂.pdfVIP

Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets 1 2 1 1 Judith M. A. van den Brand , Koert J. Stittelaar , Geert van Amerongen , Leslie Reperant , Leon de 2 1,2 1 Waal , Albert D. M. E. Osterhaus , Thijs Kuiken * 1 Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands, 2 Viroclinics Biosciences B.V., Rotterdam, The Netherlands Abstract 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