Chikungunya virus (CHIKV) is a recently re-emerged public health problem in many countries bordering the Indian Ocean and elsewhere. Chikungunya fever is a relatively self limiting febrile disease, but the consequences of chikungunya fever can include a long lasting, debilitating arthralgia, and occasional neurological involvement has been reported. Macrophages have been implicated as an important cell target of CHIKV with regards to both their role as an immune mediator, as well evidence pointing to long term viral persistence in these cells. Microglial cells are the resident brain macrophages, and so this study sought to define the proteomic changes in a human microglial cell line (CHME-5) in response to CHIKV infection. GeLC-MS/MS analysis of CHIKV infected and mock infected cells identified some 1455 individual proteins, of which 90 proteins, belonging to diverse cellular pathways, were significantly down regulated at a significance level of p<0.01. Analysis of the protein profile in response to infection did not support a global inhibition of either normal or IRES-mediated translation, but was consistent with the targeting of specific cellular pathways including those regulating innate antiviral mechanisms.

Andrographolide is a major bioactive constituent of Andrographis paniculata that has been shown in vitro to have antiviral activity against a number of viruses, including the mosquito transmitted dengue virus (DENV). However, how andrographolide exerts an anti-DENV effect remains unclear. This study therefore sought to further understand the mechanism of action of andrographolide in inhibiting DENV infection of liver cells using a proteomic based approach. Both 1 dimension (D) and 2D proteome systems were used. Initial data was generated through andrographolide treatment of HepG2 cells without DENV infection (1D analysis), while subsequent data was generated through a combination of andrographolide treatment and DENV infection (2D analysis). A total of 17 (1D) and 18 (2D) proteins were identified as differentially regulated. The analyses identified proteins involved in chaperone activities, as well as energy production. In particular evidence suggested an important role for GRP78 and the unfolded protein response in mediating the anti-DENV activity of andrographolide, which might, in part, explain the broad antiviral activity of andrographolide.