Open AccessRole of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation
Author(s) -
Suan Sin Foo,
Weiqiang Chen,
Adam Taylor,
Kuo Ching Sheng,
Xing Yu,
Terk Shin Teng,
Patrick C. Reading,
Helen Blanchard,
Cecília Garlanda,
Alberto Mantovani,
Lisa F. P. Ng,
Lara J. Herrero,
Suresh Mahalingam
Publication year - 2015
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1004649
Subject(s) - alphavirus , alphavirus infection , virology , viral replication , chikungunya , virus , sindbis virus , ptx3 , biology , immunology , pathogenesis , ross river virus , immune system , togaviridae , viral load , disease , inflammation , medicine , gene , rna , genetics
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.