a protective role for complement c3 protein during pandemic 2009 h1n1 and h5n1 influenza a virus infection补体c3蛋白质的保护作用在2009年流感大流行的h1n1病毒和h5n1流感病毒的感染.pdfVIP

A Protective Role for Complement C3 Protein during Pandemic 2009 H1N1 and H5N1 Influenza A Virus Infection 1,2 3 1 4,5,6 2 Kevin B. O’Brien , Thomas E. Morrison , David Y. Dundore , Mark T. Heise , Stacey Schultz-Cherry * 1 Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, United States of America, 2 Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America, 3 Department of Microbiology, University of Colorado–Denver, Aurora, Colorado, United States of America, 4 Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America, 5 Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America, 6 Carolina Vaccine Institute, University of North Carolina, Chapel Hill, North Carolina, United States of America 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, stud