| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia;
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia and Fondazione "Istituto di Ricovero e Cura per le Biotecnologie Trapiantologiche," Perugia;
Instituto Clinico Humanitas, Istituto Di Ricovero e Cura a Carattere Scientifico;
State University of Milan, Milan, Italy; and
¶ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Project Grant 400226 and a Programme Grant from The National Health and Medical Research Council of Australia, and by Research Grant RIGP/05/CR90 from Tecnogen Società Per Azioni Italy (to L.R.). E.C.C. was supported by Grants HL44015 and HL29594 from the National Institutes of Health. A.M. was supported by Cariplo Foundation (Project Next Generation Optical Network for Broadband European Leadership), Telethon, Project Fluinnate, and Mugen from the European Commission. P.C.R. is a National Health and Medical Research Council R. D. Wright Research Fellow.
2 Address correspondence and reprint requests to Dr. Patrick C. Reading, Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia. E-mail address: preading{at}unimelb.edu.au
3 L.R. and A.M. contributed equally to this study.
4 Abbreviations used in this paper: SP-D, surfactant protein D; SP-A, surfactant protein A; HA, hemagglutinin; NA, neuraminidase; CHO, Chinese hamster ovary; HAU, hemagglutinating unit; MDCK, Madin-Darby canine kidney; BAL, bronchoalveolar lavage; HI, hemagglutination inhibition; SA, sialic acid.
This article has been cited by other articles:
|
|
 |
|
  L. May, M. Kuningas, D. v. Bodegom, H. J. Meij, M. Frolich, P. E. Slagboom, A. Mantovani, and R. G.J. Westendorp Genetic Variation in Pentraxin (PTX) 3 Gene Associates with PTX3 Production and Fertility in Women Biol Reprod, February 1, 2010; 82(2): 299 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Tate, Y.-M. Deng, J. E. Jones, G. P. Anderson, A. G. Brooks, and P. C. Reading Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection J. Immunol., December 1, 2009; 183(11): 7441 - 7450. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
