title: Clinical response to pandemic H1N1 influenza virus from a fatal and mild case in ferrets.
abstract: 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.
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. pamela.martinez@cresa.uab.cat.
authors.forename: Pamela
authors.initials: P
authors.lastname: Martínez-Orellana
authors.affiliation: Departament de Medicina i Cirurgia Animals, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. jaumeMiquel.Martorell@uab.cat.
authors.forename: Jaume
authors.initials: J
authors.lastname: Martorell
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. beatriz.vidana@cresa.uab.es.|Departament de Sanitat i Anatomia Animals, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. beatriz.vidana@cresa.uab.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Vidaña
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Natalia.Majo@cresa.uab.cat.|Departament de Sanitat i Anatomia Animals, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. Natalia.Majo@cresa.uab.cat.
authors.forename: Natalia
authors.initials: N
authors.lastname: Majó
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Jorge.Martinez.Martinez@uab.cat.|Departament de Sanitat i Anatomia Animals, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. Jorge.Martinez.Martinez@uab.cat.
authors.forename: Jorge
authors.initials: J
authors.lastname: Martínez
authors.affiliation: Centro Nacional de Biotecnología, CSIC. Campus de la Universidad Autónoma, Cantoblanco, Madrid, Spain. afalcon@cnb.csic.es.|CIBER de Enfermedades Respiratorias, Mallorca, Illes Baleares, Spain. afalcon@cnb.csic.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Falcón
authors.affiliation: Centro Nacional de Biotecnología, CSIC. Campus de la Universidad Autónoma, Cantoblanco, Madrid, Spain. arguez@cnb.csic.es.|CIBER de Enfermedades Respiratorias, Mallorca, Illes Baleares, Spain. arguez@cnb.csic.es.|Present address: Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA. arguez@cnb.csic.es.
authors.forename: Ariel
authors.initials: A
authors.lastname: Rodríguez-Frandsen
authors.affiliation: Centro Nacional de Microbiología, ISCIII, Majadahonda, Madrid, Spain. icasas@isciii.es.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Casas
authors.affiliation: Centro Nacional de Microbiología, ISCIII, Majadahonda, Madrid, Spain. pacopozo@isciii.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Pozo
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. lourdes.migura@cresa.uab.es.
authors.forename: Lourdes
authors.initials: L
authors.lastname: García-Migura
authors.affiliation: CIBER de Enfermedades Respiratorias, Mallorca, Illes Baleares, Spain. bgarcia@isciii.es.|Centro Nacional de Microbiología, ISCIII, Majadahonda, Madrid, Spain. bgarcia@isciii.es.
authors.forename: Blanca
authors.initials: B
authors.lastname: García-Barreno
authors.affiliation: CIBER de Enfermedades Respiratorias, Mallorca, Illes Baleares, Spain. jmelero@isciii.es.|Centro Nacional de Microbiología, ISCIII, Majadahonda, Madrid, Spain. jmelero@isciii.es.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Melero
authors.affiliation: Universitat de Lleida, Lleida, Spain. lorenzo.fraile@prodan.udl.cat.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fraile
authors.affiliation: Centro Nacional de Biotecnología, CSIC. Campus de la Universidad Autónoma, Cantoblanco, Madrid, Spain. anieto@cnb.csic.es.|CIBER de Enfermedades Respiratorias, Mallorca, Illes Baleares, Spain. anieto@cnb.csic.es.
authors.forename: Amelia
authors.initials: A
authors.lastname: Nieto
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. maria.montoya@pirbright.ac.uk.|Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Barcelona, Spain. maria.montoya@pirbright.ac.uk.|Present address: The Pirbright Institute, Ash Road, Woking, GU24 0NF, Pirbright, UK. maria.montoya@pirbright.ac.uk.
authors.forename: Maria
authors.initials: M
authors.lastname: Montoya
mesh_terms: D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets / Q000821:virology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D007251:Influenza, Human / Q000097:blood / Q000473:pathology / Q000821:virology*; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral