10.1371/journal.ppat.1004649PLoS Pathogens11

Blanchard, Helen

Chen, Weiqiang

Foo, Suan-Sin

Garlanda, Cecilia

Herrero, Lara J.

Mahalingam, Suresh

Mantovani, Alberto

Ng, Fong Poh Lisa

Reading, Patrick C.

Sheng, Kuo-Ching

Taylor, Adam

Teng, Terk- Shin

Yu, Xing

PLoS Pathogens

PubMed

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

Crossref

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

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.Office of the Snr Dep Vice Chancellor, Institute for GlycomicsFull Tex

Foo, Jolin

Chen, Javier

Teng, Terk-Shin

Ng, Lisa F. P.

Herrero, Lara

Griffith Research Online

Reading, Patrick C

Ng, Lisa FP

Herrero, Lara J

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

Foo, SS

Chen, W

Taylor, A

Sheng, KC

Yu, X

Teng, TS

Reading, PC

Blanchard, H

Garlanda, C

Mantovani, A

Ng, LFP

Herrero, LJ

Mahalingam, S

University of Melbourne Institutional Repository

<div><p>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<sup>-/-</sup>) 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.</p></div

Suan-Sin Foo (693879)

Weiqiang Chen (164339)

Adam Taylor (242384)

Kuo-Ching Sheng (444505)

Xing Yu (693880)

Terk-Shin Teng (693881)

Patrick C. Reading (354655)

Helen Blanchard (693882)

Cecilia Garlanda (291677)

Alberto Mantovani (287283)

Lisa F. P. Ng (252501)

Lara J. Herrero (176060)

Suresh Mahalingam (176075)

The Francis Crick Institute

Patrick C Reading

Lisa F P Ng

Lara J Herrero

Directory of Open Access Journals

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

http://dx.doi.org/10.1371/journal.ppat.1004649

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

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Crossref

Griffith Research Online

Griffith Research Online

University of Melbourne Institutional Repository

The Francis Crick Institute

Directory of Open Access Journals