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

• Main Authors: Suan-Sin Foo, Weiqiang Chen, Adam Taylor, Kuo-Ching Sheng, Xing Yu, Terk-Shin Teng, Patrick C Reading, Helen Blanchard, Cecilia Garlanda, Alberto Mantovani, Lisa F P Ng, Lara J Herrero, Suresh Mahalingam
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2015-02-01
• Series: PLoS Pathogens
• Online Access: https://doi.org/10.1371/journal.ppat.1004649
• ISSN: 1553-7366; 1553-7374

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.