In brief

The symptoms of chikungunya virus infection, such as joint swelling, are the result of dynamic interactions between the virus and the host immune system.

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Revisiting the antiviral role of Viperin

19 Aug 2019

The antiviral protein Viperin keeps immune cells in check to prevent joint swelling during chikungunya virus infection.

Since the chikungunya virus (CHIKV) outbreaks in 2004, scientists around the world have been trying to understand how the pathogen causes its classical symptoms of fever and joint swelling which, in some cases, can last for years. The protein Viperin is known to exert a protective, antiviral effect by interfering with virus replication, although recent studies have suggested that Viperin may also regulate the host immune response during infection.

In this study, researchers led by Lisa F.P. Ng at the Singapore Immunology Network (SIgN) demonstrated that the loss of Viperin in mice is responsible for a host-damaging immune response to CHIKV infection. The team first showed that CHIKV-infected mice lacking the Viperin gene (Viperin-KO mice) had greater joint swelling than normal mice. Joint swelling was alleviated when the researchers used an antibody to deplete a subset of immune cells—CD4+ T-cells—in Viperin-KO infected mice, showing that CD4+ T-cells were responsible for more severe joint swelling during infection.

Yet, the researchers noted that the number of CD4+ T-cells and the viral burden in the joints of Viperin-KO and normal mice were almost equal. This led them to investigate the functions of the infiltrating immune cell populations. “We showed that infiltrating monocytes and T-cells have an increased activated and pathogenic state during virus infection in Viperin-KO mice compared to normal mice,” Ng said. For example, the levels of pro-inflammatory molecules such as TNFα, IL-1α, IL-1β and IL-2 were higher in the joints of infected Viperin-KO mice than normal controls, which worsened joint swelling.

Ng’s team also transferred immune cells from Viperin-KO mice into normal mice that had been depleted of their native immune system, and vice versa. This allowed them to assess whether the loss of Viperin in non-immune cells contributed towards joint swelling. Their findings revealed that non-immune cells lacking Viperin also increase the extent of joint swelling during CHIKV infection.

“These results further highlight that Viperin’s role during infections is not merely antiviral—Viperin also influences the way our body’s immune system reacts to the infection and triggers pathology. Therefore, there is a need to better understand the cellular mechanisms of Viperin on the immune system,” Ng explained, adding that this is an area her lab plans to investigate more deeply in the future.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN).

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Carissimo, G., Teo, T. H., Chan, Y. H., Lee C. Y., Lee, B. et al. Viperin controls chikungunya virus–specific pathogenic T cell IFNγ Th1 stimulation in mice. Life Science Alliance 2(1), e201900298 (2019) | article

About the Researcher

Lisa F.P. Ng obtained her PhD in molecular virology in coronaviruses from the National University of Singapore (NUS) in 2002. After joining A*STAR’s Genome Institute of Singapore (GIS) in 2002 as a Postdoctoral Fellow, she worked on viral diseases such as hepatitis, severe acute respiratory syndrome and influenza. Ng is currently the Executive Director at A*STAR Infectious Diseases Labs (ID Labs) where she focuses on the immune responses to arthritic arboviruses that are epidemic or highly endemic in the tropical region. Ng has won numerous accolades for her research, including the ASEAN ‘International Young Scientist and Technologist Award’ in 2008 and A*STAR’s ‘Most Inspiring Mentor Award’ in March 2013.

This article was made for A*STAR Research by Wildtype Media Group