title: Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation.
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-gamma-dependent effector pathway.
authors.affiliation: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bozza
authors.forename: Francesco
authors.initials: F
authors.lastname: Bistoni
authors.forename: Roberta
authors.initials: R
authors.lastname: Gaziano
authors.forename: Lucia
authors.initials: L
authors.lastname: Pitzurra
authors.forename: Teresa
authors.initials: T
authors.lastname: Zelante
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Bonifazi
authors.forename: Katia
authors.initials: K
authors.lastname: Perruccio
authors.forename: Silvia
authors.initials: S
authors.lastname: Bellocchio
authors.forename: Mariella
authors.initials: M
authors.lastname: Neri
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Iorio
authors.forename: Giovanni
authors.initials: G
authors.lastname: Salvatori
authors.forename: Rita
authors.initials: R
authors.lastname: De Santis
authors.forename: Mario
authors.initials: M
authors.lastname: Calvitti
authors.forename: Andrea
authors.initials: A
authors.lastname: Doni
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000276:immunology / Q000502:physiology*; D003587:Cytomegalovirus / Q000378:metabolism / Q000472:pathogenicity; D003713:Dendritic Cells; D006566:Herpesviridae Infections; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D007371:Interferon-gamma; D018664:Interleukin-12; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000378:metabolism / Q000472:pathogenicity*; D053594:Myeloid Differentiation Factor 88; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000502:physiology*; D000683:Serum Amyloid P-Component / Q000276:immunology / Q000502:physiology; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014775:Virus Activation; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D050838:Interferon Regulatory Factor-3; D007371:Interferon-gamma; D018664:Interleukin-12; D053594:Myeloid Differentiation Factor 88; D009419:Nerve Tissue Proteins; D000683:Serum Amyloid P-Component; D051217:Toll-Like Receptor 9; D000099153:Pentraxins; C494233:Irf3 protein, mouse; C507780:Myd88 protein, mouse