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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alphavirus Infections / immunology*
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Animals
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C-Reactive Protein / immunology*
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Cells, Cultured
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Enzyme-Linked Immunosorbent Assay
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Female
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Flow Cytometry
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Fluorescent Antibody Technique
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nerve Tissue Proteins / immunology*
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Real-Time Polymerase Chain Reaction
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Serum Amyloid P-Component / immunology*
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Transcriptome
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Transfection
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Viral Load / immunology
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Virus Replication / immunology*
Substances
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Nerve Tissue Proteins
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Serum Amyloid P-Component
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neuronal pentraxin
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PTX3 protein
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C-Reactive Protein
Grants and funding
This project was supported by funding from the Australian National Health and Medical Research Council grant to SM (grant ID 1012292). SM is the recipient of an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship (APP1059167). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.