The laboratory ferret (Mustela putorius furo) is not only susceptible to human isolates of seasonal, avian and pandemic influenza viruses, but pathogenesis and severity of the respective clinical manifestations

of these infections are to a large extent similar to those found in humans [18, 19]. Therefore, to address the hypothesis that humans at risk for vascular disease may develop clinically overt vascular thrombosis during or shortly after influenza virus infection [20], we collected plasma samples during a time course pathogenesis P5091 in vitro experiment in which ferrets were infected with seasonal-, avian- or pandemic influenza viruses [21]. Even though ferrets are not generally considered to represent the high risk patients for vascular thrombotic disease, buy SB-715992 they do offer a biologically variable and reliable animal model to address the activation of coagulation during influenza virus infection. Prothrombin time, activated partial thromboplastin time, von Willebrand factor

(VWF) activity, D-dimer levels, and thrombin-antithrombin complexes were measured in sequentially collected plasma samples. In addition fibrin staining was carried out on the lungs of infected animals upon euthanasia to address the coagulation status at the tissue level. All these parameters were evaluated in relation to virological parameters and data on disease severity. Results Clinical signs, pathology and virology of ferrets after infection with H3N2-, pH1N1- or highly pathogenic H5N1 Selleck SAR302503 avian – influenza viruses Clinical signs, pathological changes and virological parameters of this time course experiment in ferrets have been reported Monoiodotyrosine previously [21]. Data important for this study are summarized in Table 1. In

short, clinical signs varied greatly between the three influenza virus and mock infected groups. All animals infected with H3N2, pH1N1, or mock infection, survived the infections. H3N2 virus infected ferrets showed mild clinical signs; nasal discharge, sneezing, decreased tendency to eat, and bodyweight decrease by 11% (SD 8.5-13%) at 7 dpi. Detection of infectious virus was restricted to the nose and peaked at 1 dpi. Upon necropsy the lungs of the H3N2 infected ferrets showed up to 10% consolidation by gross pathology while the relative lung weights did not differ from the controls. Table 1 Overview of the clinical data (bodyweight decrease, relative lung weight, lung damage) and virological parameters (virus titers) partly adapted from Van den Brand et al. 2012 Plos One[21] Day   1 2 3 4 7 14 Bodyweight H3N2 -51 -100 -69 -124 -186 -205 (16–86) (9–190) (33–104) (117–130) (141–231) (101–309) pH1N1 -68 -169 -142 -250 -251 -193 (22–114) (161–176) (74–210) (185–315) (190–312) (19–368) H5N1 -70 -131 -170 -190 ┼ ┼ (35–105) (112–149) (142–198) (135–246)     Control -44 -20 +7 -34 -62 -46 (31–57) (+30 – -69) (+40- -25) (+19 – -88) (+10 – -134) (+30 – 123) Relative lung weight 10-2 gram H3N2 0.6 0.6 0.6 0.6 0.6 0.6 (0.5-0.7) (0.6-0.