Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere1004649
JournalPLoS Pathogens
Volume11
Issue number2
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

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