title: Antiviral activity of the long chain pentraxin PTX3 against influenza viruses.
abstract: Proteins of the innate immune system can act as natural inhibitors of influenza virus, limiting growth and spread of the virus in the early stages of infection before the induction of adaptive immune responses. In this study, we identify the long pentraxin PTX3 as a potent innate inhibitor of influenza viruses both in vitro and in vivo. Human and murine PTX3 bound to influenza virus and mediated a range of antiviral activities, including inhibition of hemagglutination, neutralization of virus infectivity and inhibition of viral neuraminidase. Antiviral activity was associated with binding of the viral hemagglutinin glycoprotein to sialylated ligands present on PTX3. Using a mouse model we found PTX3 to be rapidly induced following influenza infection and that PTX3-/- mice were more susceptible than wild-type mice to infection by PTX3-sensitive virus strains. Therapeutic treatment of mice with human PTX3 promoted survival and reduced viral load in the lungs following infection with PTX3-sensitive, but not PTX3-resistant, influenza viruses. Together, these studies describe a novel antiviral role for PTX3 in early host defense against influenza infections both in vitro and in vivo and describe the therapeutic potential of PTX3 in ameliorating disease during influenza infection.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia. preading@unimelb.edu.au
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
authors.forename: Silvia
authors.initials: S
authors.lastname: Bozza
authors.forename: Brad
authors.initials: B
authors.lastname: Gilbertson
authors.forename: Michelle
authors.initials: M
authors.lastname: Tate
authors.forename: Silvia
authors.initials: S
authors.lastname: Moretti
authors.forename: Emma R
authors.initials: ER
authors.lastname: Job
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Lorena E
authors.initials: LE
authors.lastname: Brown
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D000209:Acute-Phase Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002097:C-Reactive Protein / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D002645:Chickens; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D011485:Protein Binding / Q000276:immunology; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D013329:Structure-Activity Relationship; D000099153:Pentraxins
chemical_list: D000209:Acute-Phase Proteins; D000998:Antiviral Agents; D002097:C-Reactive Protein; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D019158:N-Acetylneuraminic Acid; D009419:Nerve Tissue Proteins; D009439:Neuraminidase; D037663:Pulmonary Surfactant-Associated Protein D; D000683:Serum Amyloid P-Component; D000099153:Pentraxins