Comparative Pathology of Select Agent Influenza A Virus Infections

Abstract

Influenza A virus infections may spread rapidly in human populations and cause variable mortality. Two of these influenza viruses have been designated as select agents: 1918 H1N1 virus and highly pathogenic avian influenza (HPAI) virus. Knowledge of the pathology of these virus infections in humans, other naturally infected species, and experimental animals is important to understand the pathogenesis of influenza, to design appropriate models for evaluation of medical countermeasures, and to make correct diagnoses. The most important complication of influenza in humans is viral pneumonia, which often occurs with or is followed by bacterial pneumonia. Viremia and extrarespiratory disease are uncommon. HPAI viruses, including HPAI H5N1 virus, cause severe systemic disease in galliform species as well as in anseriform species and bird species of other orders. HPAI H5N1 virus infection also causes severe disease in humans and several species of carnivores. Experimental animals are used to model different aspects of influenza in humans, including uncomplicated influenza, pneumonia, and virus transmission. The most commonly used experimental animal species are laboratory mouse, domestic ferret, and cynomolgus macaque. Experimental influenza virus infections are performed in various other species, including domestic pig, guinea pig, and domestic cat. Each of these species has advantages and disadvantages that need to be assessed before choosing the most appropriate model to reach a particular goal. Such animal models may be applied for the development of more effective antiviral drugs and vaccines to protect humans from the threat of these virus infections.

Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic avian influenza H5N1 Virus Infections in Ferrets

“…In negative control animals (non-inoculated) the median number (range) of mononuclear cells is 0. 30 10 9 /L (0.13-0.37) in the blood and 17 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) in the alveolar lumina, for neutrophils 4.33 (3.07-7.28) in the blood and 0.5 (0-2) in the alveolar lumina. doi:10.1371/journal.pone.0042343.g009 Table 5.…”

“…In the lungs, there was a mild multifocal bronchitis and bronchiolitis with intra-epithelial neutrophils, mild peribronchiolar and perivascular cuffing, mild broncho-adenitis, and mild multifocal alveolitis with mild intra-epithelial infiltration of neutrophils with mild epithelial necrosis and mild edema in the alveolar lumina. By immunohistochemistry, influenza virus antigen expression was visible as diffuse to granular red staining, which usually was stronger in the nucleus than in the cytoplasm (Figures 3,4,5,6,7,8). Antigen expression in the nose was present from 0.5 to 4 dpi, while no antigen expression was seen in the tracheal, bronchial, bronchiolar, and tracheo-bronchial glandular epithelium at any time point, and little antigen expression in few type II pneumocytes in the alveoli.…”

“…By histopathology, there was a mild to moderate multifocal rhinitis with necrosis of the epithelium and mild multifocal tracheitis. In the lungs, there was a moderate multifocal bronchitis and bronchiolitis, with intra-epithelial and intraluminal neutrophils, mild to moderate epithelial necrosis, and mild peribronchiolar and perivascular cuffing; a mild to severe broncho-adenitis; and a severe multifocal to diffuse alveolitis, with severe epithelial necrosis, intra-epithelial and intraluminal infiltration of neutrophils, severe intraluminal edema, and hypertrophy and hyperplasia of epithelial cells (Figures 4,5,6,7,8). The tracheo-bronchial lymph nodes and tonsils demonstrated lymphadenopathy.…”

Patho-Morphological And Clinical Examinations In Experimental Infection Of Guinea Fowl (Numida Meleagris) With Lpaiv H6n2

“…The high extent of spread of HPAIV H5N1 among birds has led to establishing infection in guinea fowl as well (3). In Kenya, guinea fowl isolates are available in H5N1 outbreaks (4).…”

Early host response and immune signaling to 2009 pandemic influenza A (H1N1) viruses in primary cell culture models.

“…Immunopathology at the site of influenza infection suggests a role for immune cells infiltrates in severe influenza infection [308,309]. Production of proinflammatory cytokines by virus-infected monocyte/macrophages can potentially 2) To compare infection and dynamics of the host response to genetically similar H1N1pdm IAV isolates in human monocyte-derived macrophages (MDM).…”