Clinical response to pandemic h1n1 influenza virus from a fatal and mild case in ferrets

Virology Journal, Mar 2015

Background The majority of pandemic 2009 H1N1 (A(H1N1)pdm09) influenza virus (IV) caused mild symptoms in most infected patients, however, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. The purpose of this work was to study in ferrets the dynamics of infection of two contemporary strains of human A(H1N1)pdm09 IV, one isolated from a patient showing mild disease and the other one from a fatal case. Methods Viral strains isolated from a patient showing mild disease-M (A/CastillaLaMancha/RR5661/2009) or from a fatal case-F (A/CastillaLaMancha/RR5911/2009), both without known comorbid conditions, were inoculated in two groups of ferrets and clinical and pathological conditions were analysed. Results Mild to severe clinical symptoms were observed in animals from both groups. A clinical score distribution was applied in which ferrets with mild clinical signs were distributed on a non-severe group (NS) and ferrets with severe clinical signs on a severe group (S), regardless of the virus used in the infection. Animals on S showed a significant decrease in body weight compared to animals on NS at 4 to 7 days post-infection (dpi). Clinical progress correlated with histopathological findings. Concentrations of haptoglobin (Hp) and serum amyloid A (SAA) increased on both groups after 2 dpi. Clinically severe infected ferrets showed a stronger antibody response and higher viral titres after infection (p = 0.001). Conclusions The severity in the progress of infection was independent from the virus used for infection suggesting that the host immune response was determinant in the outcome of the infection. The diversity observed in ferrets mimicked the variability found in the human population.

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Clinical response to pandemic h1n1 influenza virus from a fatal and mild case in ferrets

Martnez-Orellana et al. Virology Journal Clinical response to pandemic h1n1 influenza virus from a fatal and mild case in ferrets Pamela Martnez-Orellana 0 5 Jaume Martorell 3 Beatriz Vidaa 0 2 5 Natalia Maj 0 2 5 Jorge Martnez 0 2 5 Ana Falcn 8 9 Ariel Rodrguez-Frandsen 4 8 9 Inmaculada Casas 7 Francisco Pozo 7 Lourdes Garca-Migura 0 5 Blanca Garca-Barreno 7 8 Jose A Melero 7 8 Lorenzo Fraile 6 Amelia Nieto 8 9 Maria Montoya 0 1 5 10 11 0 Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autonoma de Barcelona , Bellaterra, Barcelona , Spain 1 Institut de Recerca i Tecnologia Agroalimentaries (IRTA) , Barcelona , Spain 2 Departament de Sanitat i Anatomia Animals, Universitat Autonoma de Barcelona (UAB) , Barcelona , Spain 3 Departament de Medicina i Cirurgia Animals, Universitat Autonoma de Barcelona (UAB) , Barcelona , Spain 4 Present address: Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute , La Jolla, CA , USA 5 Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autonoma de Barcelona , Bellaterra, Barcelona , Spain 6 Universitat de Lleida , Lleida , Spain 7 Centro Nacional de Microbiologia, ISCIII , Majadahonda, Madrid , Spain 8 CIBER de Enfermedades Respiratorias , Mallorca, Illes Baleares , Spain 9 Centro Nacional de Biotecnologia, CSIC. Campus de la Universidad Autonoma , Cantoblanco, Madrid , Spain 10 Present address: The Pirbright Institute , Ash Road, Woking, GU24 0NF, Pirbright , UK 11 Institut de Recerca i Tecnologia Agroalimentaries (IRTA) , Barcelona , Spain Background: The majority of pandemic 2009 H1N1 (A(H1N1)pdm09) influenza virus (IV) caused mild symptoms in most infected patients, however, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. The purpose of this work was to study in ferrets the dynamics of infection of two contemporary strains of human A(H1N1)pdm09 IV, one isolated from a patient showing mild disease and the other one from a fatal case. Methods: Viral strains isolated from a patient showing mild disease-M (A/CastillaLaMancha/RR5661/2009) or from a fatal case-F (A/CastillaLaMancha/RR5911/2009), both without known comorbid conditions, were inoculated in two groups of ferrets and clinical and pathological conditions were analysed. Results: Mild to severe clinical symptoms were observed in animals from both groups. A clinical score distribution was applied in which ferrets with mild clinical signs were distributed on a non-severe group (NS) and ferrets with severe clinical signs on a severe group (S), regardless of the virus used in the infection. Animals on S showed a significant decrease in body weight compared to animals on NS at 4 to 7 days post-infection (dpi). Clinical progress correlated with histopathological findings. Concentrations of haptoglobin (Hp) and serum amyloid A (SAA) increased on both groups after 2 dpi. Clinically severe infected ferrets showed a stronger antibody response and higher viral titres after infection (p = 0.001). Conclusions: The severity in the progress of infection was independent from the virus used for infection suggesting that the host immune response was determinant in the outcome of the infection. The diversity observed in ferrets mimicked the variability found in the human population. Pandemic A(H1N1)pdm09; Clinical response; Ferrets - Introduction Influenza A viruses are classified as members of the family Orthomyxoviridae. They are classified according their haemagglutinin (HA) and neuraminidase (NA) molecules, which are the basis of the antigenicity [1]. They can produce significant respiratory disease in humans and in a whole range of avian and mammals species. In some occasions, simultaneous infection in a susceptible species by more than one influenza A viruses can lead to gene mixing, or reassortment. These processes can originate a novel influenza virus strain, against which human population would have few or no existing immunity [2]. A new influenza A virus from H1N1 subtype, possessing high transmissibility but relatively low virulence, emerged in 2009 (A(H1N1)pdm09) rapidly spreading across the entire globe and causing the first pandemic of the 21st century. It carried genes of avian, swine and human IV [3,4]. Nowadays, A(H1N1)pdm09 still remain being an important issue of public health, and in general terms, A(H1N1)pdm09 infection can cause mild and self-limiting symptoms [5]. However, in some cases the disease progresses towards severity, exhibiting symptoms that have been characterized by severe or complicated illness, often requiring hospitalization and mortality [6-8]. Previous studies in our group indicated that the virus isolated from the fatal case replicates faster, induces higher levels of cytokines in human alveolar lung epithelial cells and is more pathogenic in a murine model in vivo, compared with the virus obtained from the patient with mild disease (...truncated)


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Pamela Martínez-Orellana, Jaume Martorell, Beatriz Vidaña, Natalia Majó, Jorge Martínez, Ana Falcón, Ariel Rodríguez-Frandsen, Inmaculada Casas, Francisco Pozo, Lourdes García-Migura, Blanca García-Barreno, Jose A Melero, Lorenzo Fraile, Amelia Nieto, Maria Montoya. Clinical response to pandemic h1n1 influenza virus from a fatal and mild case in ferrets, Virology Journal, 2015, pp. 48, 12, DOI: 10.1186/s12985-015-0272-x