Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation
Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by Aspergillus species (spp). Antimicrobial polypeptides, including defensins and mannan-binding lect...
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Published in | Blood Vol. 108; no. 10; pp. 3387 - 3396 |
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Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Washington, DC
Elsevier Inc
15.11.2006
The Americain Society of Hematology |
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Abstract | Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by Aspergillus species (spp). Antimicrobial polypeptides, including defensins and mannan-binding lectin, are known to block viral fusion by cross-linking sugars on cell surface. Pentraxin 3 (PTX3), a member of the long pentraxin family, successfully restored antifungal immunity in experimental hematopoietic transplantation. We assessed here whether PTX3 binds HCMV and murine virus (MCMV) and the impact on viral infectivity and superinfection in vivo. We found that PTX3 bound both viruses, reduced viral entry and infectivity in vitro, and protected from MCMV primary infection and reactivation as well as Aspergillus superinfection. This occurred through the activation of interferon (IFN) regulatory factor 3 (IRF3) in dendritic cells via the TLR9/MyD88-independent viral recognition sensing and the promotion of the interleukin-12 (IL-12)/IFN-γ–dependent effector pathway. |
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AbstractList | Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by Aspergillus species (spp). Antimicrobial polypeptides, including defensins and mannan-binding lectin, are known to block viral fusion by cross-linking sugars on cell surface. Pentraxin 3 (PTX3), a member of the long pentraxin family, successfully restored antifungal immunity in experimental hematopoietic transplantation. We assessed here whether PTX3 binds HCMV and murine virus (MCMV) and the impact on viral infectivity and superinfection in vivo. We found that PTX3 bound both viruses, reduced viral entry and infectivity in vitro, and protected from MCMV primary infection and reactivation as well as Aspergillus superinfection. This occurred through the activation of interferon (IFN) regulatory factor 3 (IRF3) in dendritic cells via the TLR9/MyD88-independent viral recognition sensing and the promotion of the interleukin-12 (IL-12)/IFN-γ–dependent effector pathway. Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by Aspergillus species (spp). Antimicrobial polypeptides, including defensins and mannan-binding lectin, are known to block viral fusion by cross-linking sugars on cell surface. Pentraxin 3 (PTX3), a member of the long pentraxin family, successfully restored antifungal immunity in experimental hematopoietic transplantation. We assessed here whether PTX3 binds HCMV and murine virus (MCMV) and the impact on viral infectivity and superinfection in vivo. We found that PTX3 bound both viruses, reduced viral entry and infectivity in vitro, and protected from MCMV primary infection and reactivation as well as Aspergillus superinfection. This occurred through the activation of interferon (IFN) regulatory factor 3 (IRF3) in dendritic cells via the TLR9/MyD88-independent viral recognition sensing and the promotion of the interleukin-12 (IL-12)/IFN-gamma-dependent effector pathway. Abstract Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by Aspergillus species (spp). Antimicrobial polypeptides, including defensins and mannan-binding lectin, are known to block viral fusion by cross-linking sugars on cell surface. Pentraxin 3 (PTX3), a member of the long pentraxin family, successfully restored antifungal immunity in experimental hematopoietic transplantation. We assessed here whether PTX3 binds HCMV and murine virus (MCMV) and the impact on viral infectivity and superinfection in vivo. We found that PTX3 bound both viruses, reduced viral entry and infectivity in vitro, and protected from MCMV primary infection and reactivation as well as Aspergillus superinfection. This occurred through the activation of interferon (IFN) regulatory factor 3 (IRF3) in dendritic cells via the TLR9/MyD88-independent viral recognition sensing and the promotion of the interleukin-12 (IL-12)/IFN-γ–dependent effector pathway. |
Author | Iorio, Anna Maria Calvitti, Mario Romani, Luigina Perruccio, Katia Gaziano, Roberta Mantovani, Alberto Salvatori, Giovanni Doni, Andrea Bozza, Silvia Bistoni, Francesco Bonifazi, Pierluigi De Santis, Rita Neri, Mariella Zelante, Teresa Pitzurra, Lucia Bellocchio, Silvia Garlanda, Cecilia |
Author_xml | – sequence: 1 givenname: Silvia surname: Bozza fullname: Bozza, Silvia – sequence: 2 givenname: Francesco surname: Bistoni fullname: Bistoni, Francesco – sequence: 3 givenname: Roberta surname: Gaziano fullname: Gaziano, Roberta – sequence: 4 givenname: Lucia surname: Pitzurra fullname: Pitzurra, Lucia – sequence: 5 givenname: Teresa surname: Zelante fullname: Zelante, Teresa – sequence: 6 givenname: Pierluigi surname: Bonifazi fullname: Bonifazi, Pierluigi – sequence: 7 givenname: Katia surname: Perruccio fullname: Perruccio, Katia – sequence: 8 givenname: Silvia surname: Bellocchio fullname: Bellocchio, Silvia – sequence: 9 givenname: Mariella surname: Neri fullname: Neri, Mariella – sequence: 10 givenname: Anna Maria surname: Iorio fullname: Iorio, Anna Maria – sequence: 11 givenname: Giovanni surname: Salvatori fullname: Salvatori, Giovanni – sequence: 12 givenname: Rita surname: De Santis fullname: De Santis, Rita – sequence: 13 givenname: Mario surname: Calvitti fullname: Calvitti, Mario – sequence: 14 givenname: Andrea surname: Doni fullname: Doni, Andrea – sequence: 15 givenname: Cecilia surname: Garlanda fullname: Garlanda, Cecilia – sequence: 16 givenname: Alberto surname: Mantovani fullname: Mantovani, Alberto – sequence: 17 givenname: Luigina surname: Romani fullname: Romani, Luigina email: lromani@unipg.it |
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Keywords | Murine cytomegalovirus Herpesviridae Rodentia Pentraxine PTX3 Betaherpesvirinae Biological activity Toll like receptor 9 Human cytomegalovirus Fungi Virus Infection Aspergillus Vertebrata Mammalia Mouse Interferon regulatory factor 3 Animal Antiviral Fungi Imperfecti Thallophyta |
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Snippet | Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe... Abstract Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes... |
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SubjectTerms | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences C-Reactive Protein - immunology C-Reactive Protein - physiology Cytomegalovirus - metabolism Cytomegalovirus - pathogenicity Dendritic Cells Herpesviridae Infections Human viral diseases Infectious diseases Interferon Regulatory Factor-3 - metabolism Interferon-gamma Interleukin-12 Medical sciences Mice Mice, Knockout Muromegalovirus - metabolism Muromegalovirus - pathogenicity Myeloid Differentiation Factor 88 Nerve Tissue Proteins - immunology Nerve Tissue Proteins - physiology Pharmacology. Drug treatments Serum Amyloid P-Component - immunology Serum Amyloid P-Component - physiology Signal Transduction Toll-Like Receptor 9 - metabolism Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Virus Activation |
Title | Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation |
URI | https://dx.doi.org/10.1182/blood-2006-03-009266 https://www.ncbi.nlm.nih.gov/pubmed/16840729 https://search.proquest.com/docview/68113506 |
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