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

Journal Article


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.

UOW Authors


  •   Blanchard, Helen (external author)

Publication Date


  • 2015

Citation


  • Foo, S. S., Chen, W., Taylor, A., Sheng, K. C., Yu, X., Teng, T. S., . . . Mahalingam, S. (2015). Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation. PLoS Pathogens, 11(2). doi:10.1371/journal.ppat.1004649

Scopus Eid


  • 2-s2.0-84924347577

Volume


  • 11

Issue


  • 2

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.

UOW Authors


  •   Blanchard, Helen (external author)

Publication Date


  • 2015

Citation


  • Foo, S. S., Chen, W., Taylor, A., Sheng, K. C., Yu, X., Teng, T. S., . . . Mahalingam, S. (2015). Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation. PLoS Pathogens, 11(2). doi:10.1371/journal.ppat.1004649

Scopus Eid


  • 2-s2.0-84924347577

Volume


  • 11

Issue


  • 2