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PLoS Pathog. 2015 Feb 19;11(2):e1004649. doi: 10.1371/journal.ppat.1004649. eCollection 2015 Feb.

Role of pentraxin 3 in shaping arthritogenic alphaviral disease: from enhanced viral replication to immunomodulation.

Author information

1
Institute for Glycomics, Griffith University, Gold Coast, Australia.
2
Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
3
WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
4
Humanitas Clinical and Research Center, Department of Inflammation and Immunology, Rozzano, Italy.
5
Humanitas Clinical and Research Center, Department of Inflammation and Immunology, Rozzano, Italy; Department of Biotechnology and Translational Medicine, University of Milan, Milano, Italy.
6
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.

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.

PMID:
25695775
PMCID:
PMC4335073
DOI:
10.1371/journal.ppat.1004649
[Indexed for MEDLINE]
Free PMC Article

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