Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation

• Published in: Blood Vol. 108; no. 10; pp. 3387 - 3396
• Main Authors: Bozza, Silvia, Bistoni, Francesco, Gaziano, Roberta, Pitzurra, Lucia, Zelante, Teresa, Bonifazi, Pierluigi, Perruccio, Katia, Bellocchio, Silvia, Neri, Mariella, Iorio, Anna Maria, Salvatori, Giovanni, De Santis, Rita, Calvitti, Mario, Doni, Andrea, Garlanda, Cecilia, Mantovani, Alberto, Romani, Luigina
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.11.2006; The Americain Society of Hematology
• Subjects: 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; 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
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-03-009266

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.