How Do Mosquito-Borne Viruses Cause Arthritis? New Study Gives Answers

Mosquitoes transmit Chikungunya virus (CHIKV) and Ross River virus (RRV), and people infected with these viruses can experience arthritis, muscle pain, and fever.

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New Delhi: Researchers from Griffith University have found that some therapies successful in treating rheumatoid arthritis (RA) may help people better understand how to deal with enervating mosquito-borne viral diseases. 

Mosquitoes transmit Chikungunya virus (CHIKV) and Ross River virus (RRV), and people infected with these viruses can experience arthritis, muscle pain, and fever. Moreover, there are currently no specific drugs or therapies to prevent these symptoms. 

The findings were published in the form of two studies in two different journals, PLoS Pathogens and mBio. 

Disease Caused By Infection With Chikungunya Virus Or Ross River Virus Similar To Rheumatoid Arthritis

Quoting lead author Dr Ali Zaid from Menzies Health Institute Queensland, a statement issued by Griffith University said that the disease caused by these viral infections bears several similarities with a form of auto-immune arthritis known as rheumatoid arthritis (RA). Zaid said that patients express high levels of an immune molecule called Interleukin-17 (or IL-17) in severe rheumatoid arthritis. This is a target of new anti-arthritis drugs, the author said. 

In the studies, the authors asked whether IL-17 was also seen in CHIKV and RRV infections, and whether it could be similarly targeted to reduce arthritic disease. 

Higher Levels Of Immune Molecule IL-17 In Chronic CHIKV Patients Than Healthy Controls

The researchers, in collaboration with Professor Roque Almeida from the University Hospital, Federal University of Sergipe in Brazil, analysed serum samples from patients infected with Chikungunya virus, collected during the 2019 outbreak in northern Brazil. The research team found that while some patients with acute disease showed elevated IL-17 levels, chronic CHIKV patients showed a significantly higher increase in levels compared to healthy controls, according to the research.

Helen Mostafavi, whose PhD project investigated the role of IL-17 in RRV infection, said that when the researchers looked at serum samples from Ross River virus infections from a particular study, they found the levels of IL-17 to be elevated. This prompted the researchers to ask whether the molecule was driving the disease. 

Helen said that the researchers used an experimental mouse model of viral arthritis, and found that targeting IL-17 in virus-infected mice ameliorated disease and reduced inflammation. This demonstrated the fact that some therapies that have been successful in treating rheumatoid arthritis could be of potential benefit to treat people with alphavirus disease. Alphaviruses, which constitute a genus of more than 30 viruses in the Togaviridae family, are lipid-enveloped, positive-sense RNA viruses. All human pathogenic alphaviruses are mosquito borne.

The researchers observed that a complete lack of IL-17 was not necessarily ideal. According to the research, genetically modified mice which lack IL-17 showed an increase in viral RNA in the post-acute phase of disease. An increase in viral RNA was observed despite the mice showing reduced inflammation. 

Dr Xiang Liu, who co-authored the study, said that the findings had implications for viral persistence. He said that targeting IL-17 in alphavirus disease should be approached with caution. 

TRIF Protein Helps Generate Antibodies Against Ross River Virus

The authors, in a separate study published in mBio, investigated the role of a protein called TRIF, which stands for TIR-domain-containing adapter-inducing interferon-β. This protein uses cells to ‘sense’ viral RNA and start a strong antiviral response. This response alerts neighbouring cells. The authors used genetically modified mice that lack the TRIF protein, and found that the protein was needed to help generate antibodies against Ross River virus.

Liu said that this was surprising because the researchers knew that TRIF was very important in early antiviral responses, which occur soon after infection.

He said that the researchers found this molecule was also important in supporting antibody responses that provide long-term immunity and reduce persistent viral infections. 

Liu concluded that these findings give new insights into how different arms of the immune response cooperate to ensure long-lasting defence against viruses like Chikungunya virus and Ross River virus and “will pave the way into the development of new immunotherapies to treat these diseases.”