Introduction

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. Herein, the role of pentraxin 3 (PTX3), an acute phase innate immune protein, in facilitating alphaviral disease progression was characterised.

Methods

PTX3 expressions in PBMC and serum specimens of CHIKV-/RRV-infected patients were determined using qRT-PCR and ELISA, respectively. PTX3-deficient (PTX3-/-)/wildtype (WT) C57BL/6 mice were infected with RRV and monitored for disease. Profiles of immune mediators were determined using qRT-PCR. HEK293T cells were transiently transfected with PTX3 plasmids prior to RRV/CHIKV infection. Virus burden were determined using plaque assay and viral load qRT-PCR. 

Results

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. RRV-infected PTX3-/- mice exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Transient overexpression of PTX3 in HEK293T cells resulted in enhanced viral entry and replication during RRV/CHIKV infection, leading to high viral burden. N-terminus of PTX3 was identified to be the functional domain modulating alphaviral infection.

Conclusion 

This study demonstrates a previously undescribed pivotal role of PTX3 in shaping alphaviral disease progression through immunomodulation and facilitating viral infection and replication processes during the acute infection. Understanding the complex immune responses elicited during alphaviral infection will be integral for future development of therapeutic interventions.