title: Role of pentraxin 3 in shaping arthritogenic alphaviral disease: from enhanced viral replication to immunomodulation.
abstract: The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV) and Ross River virus (RRV), and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3) was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/-)) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Australia.
authors.forename: Suan-Sin
authors.initials: SS
authors.lastname: Foo
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Australia.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Australia.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Sheng
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Australia.
authors.forename: Xing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Terk-Shin
authors.initials: TS
authors.lastname: Teng
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Blanchard
authors.affiliation: Humanitas Clinical and Research Center, Department of Inflammation and Immunology, Rozzano, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.affiliation: Humanitas Clinical and Research Center, Department of Inflammation and Immunology, Rozzano, Italy; Department of Biotechnology and Translational Medicine, University of Milan, Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Australia.
authors.forename: Lara J
authors.initials: LJ
authors.lastname: Herrero
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Australia.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mahalingam
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology*; D000818:Animals; D002097:C-Reactive Protein / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D000683:Serum Amyloid P-Component / Q000276:immunology*; D059467:Transcriptome; D014162:Transfection; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D000683:Serum Amyloid P-Component; D000099153:Pentraxins