title: A protective role for complement C3 protein during pandemic 2009 H1N1 and H5N1 influenza A virus infection.
abstract: Highly pathogenic H5N1 influenza infections are associated with enhanced inflammatory and cytokine responses, severe lung damage, and an overall dysregulation of innate immunity. C3, a member of the complement system of serum proteins, is a major component of the innate immune and inflammatory responses. However, the role of this protein in the pathogenesis of H5N1 infection is unknown. Here we demonstrate that H5N1 influenza virus infected mice had increased levels of C5a and C3 activation byproducts as compared to mice infected with either seasonal or pandemic 2009 H1N1 influenza viruses. We hypothesized that the increased complement was associated with the enhanced disease associated with the H5N1 infection. However, studies in knockout mice demonstrated that C3 was required for protection from influenza infection, proper viral clearance, and associated with changes in cellular infiltration. These studies suggest that although the levels of complement activation may differ depending on the influenza virus subtype, complement is an important host defense mechanism.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: O'Brien
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Morrison
authors.forename: David Y
authors.initials: DY
authors.lastname: Dundore
authors.forename: Mark T
authors.initials: MT
authors.lastname: Heise
authors.forename: Stacey
authors.initials: S
authors.lastname: Schultz-Cherry
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000172:deficiency / Q000276:immunology*; D015936:Complement C5a / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000150:complications; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000150:complications / Q000453:epidemiology / Q000276:immunology* / Q000821:virology*; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology / Q000821:virology; D058873:Pandemics; D020011:Protective Agents / Q000378:metabolism*; D012621:Seasons
chemical_list: D003176:Complement C3; D020011:Protective Agents; D015936:Complement C5a