Neutralizing inhibitors in the airways of naïve ferrets do not play a major role in modulating the virulence of H3 subtype influenza A viruses.
Many insights regarding the pathogenesis of human influenza A virus (IAV) infections have come from studies in mice and ferrets. Surfactant protein (SP)-D is the major neutralizing inhibitor of IAV in mouse airway fluids and SP-D-resistant IAV mutants show enhanced virus replication and virulence in mice. Herein, we demonstrate that sialylated glycoproteins, rather than SP-D, represent the major neutralizing inhibitors against H3 subtype viruses in airway fluids from naïve ferrets. Moreover, while resistance to neutralizing inhibitors is a critical factor in modulating virus replication and disease in the mouse model, it does not appear to be so in the ferret model, as H3 mutants resistant to either SP-D or sialylated glycoproteins in ferret airway fluids did not show enhanced virulence in ferrets. These data have important implications for our understanding of pathogenesis and immunity to human IAV infections in these two widely used animal models of infection.
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
Emma R
ER
Job
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
Angela
A
Pizzolla
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Thomas
T
Nebl
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
Kirsty R
KR
Short
WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
Yi-Mo
YM
Deng
WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
Louise
L
Carolan
WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
Karen L
KL
Laurie
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
Andrew G
AG
Brooks
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia. Electronic address: preading@unimelb.edu.au.
Patrick C
PC
Reading
D000818:Animals; D005260:Female; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D009980:Influenza A virus / Q000145:classification / Q000472:pathogenicity / Q000502:physiology*; D008297:Male; D051379:Mice; D009154:Mutation; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014774:Virulence / Q000235:genetics
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037663:Pulmonary Surfactant-Associated Protein D
Animal model; Influenza; Innate; Lectin; Surfactant; Virulence