Nav: Home

Mechanism that triggers the inflammatory process by Mayaro virus is discovered

December 02, 2019

The mechanism by which defense cells respond to infection by Mayaro virus has been described by a team affiliated with the Center for Research on Inflammatory Diseases - CRID in an article published in the journal PLOS Pathogens.

According to the authors, by establishing an experimental model of Mayaro fever in adult mice and identifying the processes involved in the immune response, the study provides a basis for the development of drugs against this disease.

CRID is one of the Research, Innovation and Dissemination Centers - RIDCs funded by FAPESP (São Paulo Research Foundation). It is hosted by the University of São Paulo's Ribeirão Preto Medical School (FMRP-USP) in São Paulo state, Brazil.

Mayaro fever is a mosquito-borne viral disease similar to chikungunya fever. The symptoms include fever, rash, headache and muscle pain. The most severe cases also involve joint pain (arthralgia) with or without edema. Mayaro virus recently emerged from the Brazilian Amazon forest to circulate in the Southeast Region. Two cases of Mayaro fever have been reported in Niterói (Rio de Janeiro state), and two have been reported in São Carlos (São Paulo state).

"Mayaro fever is highly inflammatory. Its symptoms can last for months. The good news is that the inflammation is triggered by a defense mechanism that has been widely studied and is well understood," said Dario Simões Zamboni, a researcher with CRID and the last author of the article.

Zamboni is referring to multiprotein intracellular complexes known as inflammasomes. When this cellular machinery is activated, proinflammatory molecules are produced to tell the immune system that it must send more defense cells to the infection site.

Inflammasomes are also involved in autoimmune disorders, neurodegenerative diseases, some kinds of cancer, and other infectious diseases, such as Zika virus disease and chikungunya fever. In regard to Mayaro virus, the group discovered that triggering inflammasomes by activating the protein NLRP3 increased the production of interleukin-1 beta (IL-1β), a proinflammatory cytokine that plays a key role in immune system signaling.

In this study, researchers developed models of cellular infection in macrophages (white blood cells that are part of the first line of defense) and mice. The experiments showed that Mayaro virus triggered expression of proteins NLRP3, ASC and CASP1, the ones responsible for activating the immune system's inflammatory response or inflammasomes. NLRP3 was particularly important because of its essential role in the production of immune system signaling molecules.

The authors also showed that the virus activated the NLRP3 inflammasome by inducing the production of reactive oxygen species and potassium efflux from cells into the extracellular space.

In experiments with mice engineered to not express NLRP3, the group confirmed the protein's role in foot pain, swelling and inflammation. "In addition to the experiments in cultured cells and the animal model, we also compared the results with findings for blood serum collected from patients infected by Mayaro virus in the state of Mato Grosso," Zamboni explained. "The patients were found to have far higher levels of CASP1, IL-1β and interleukin-18 [IL-18] than healthy subjects, evidencing activation of the NLRP3 inflammasome in response to infection by Mayaro virus in humans."

Emerging virus

According to Luiza Castro-Jorge, a virologist and the first author of the article, Mayaro virus is considered an emerging virus that at any moment may cause major outbreaks in Brazil. "Researchers at the Federal University of Rio de Janeiro [UFRJ] and FMRP-USP have discovered that Mayaro virus is circulating in the Southeast Region," she said.

The virus is transmitted to humans by the bite of an infected wild mosquito of the genus Haemagogus, which also transmits sylvatic yellow fever.

Although several inflammasomes have been described, the NLRP3 inflammasome is the most studied, which is noted by the researchers in the article. "Drugs are being tested to inhibit the gene for NLRP3 and could, in the future, be used to make the disease less severe in patients," Zamboni said.
-end-
About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

Fundação de Amparo à Pesquisa do Estado de São Paulo

Related Immune System Articles:

Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
First impressions go a long way in the immune system
An algorithm that predicts the immune response to a pathogen could lead to early diagnosis for such diseases as tuberculosis
Filming how our immune system kill bacteria
To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets.
Putting the break on our immune system's response
Researchers have discovered how a tiny molecule known as miR-132 acts as a 'handbrake' on our immune system -- helping us fight infection.
Decoding the human immune system
For the first time ever, researchers are comprehensively sequencing the human immune system, which is billions of times larger than the human genome.
Masterswitch discovered in body's immune system
Scientists have discovered a critical part of the body's immune system with potentially major implications for the treatment of some of the most devastating diseases affecting humans.
How a fungus can cripple the immune system
An international research team led by Professor Oliver Werz of Friedrich Schiller University, Jena, has now discovered how the fungus knocks out the immune defenses, enabling a potentially fatal fungal infection to develop.
How the immune system protects us against bowel cancer
Researchers from Charité - Universitätsmedizin Berlin have discovered a protective mechanism which is used by the body to protect intestinal stem cells from turning cancerous.
How herpesviruses shape the immune system
DZIF scientists at the Helmholtz Zentrum München have developed an analytic method that can very precisely detect viral infections using immune responses.
More Immune System News and Immune System Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab