Research identifies immune response that controls Oropouche infection and prevents neurological damage

Research conducted on mice has identified that the rapid response of a specific type of defense cell is essential for controlling Oropouche virus infections and preventing serious neurological damage. Without treatment, “Oropouche fever” causes symptoms including headaches, muscle and joint pain, skin rashes, and vomiting. In severe cases, it can lead to meningitis and encephalitis. Pregnant women are at risk of complications, including miscarriage.

These findings will contribute to future studies on developing therapies and vaccines against the disease. The Oropouche virus is considered a neglected arbovirus that is transmitted by the midge Culicoides paraensis when it is infected with Orthobunyavirus oropoucheense (OROV). Between January and early June of this year, Brazil recorded a more than 60% increase in cases compared to the same period in 2024 – approximately 11,500 confirmed cases (compared to 7,200 last year) and four deaths. This total in just under six months is close to the number of cases recorded during the whole of last year – 13,800 according to the Brazilian Ministry of Health. 

The scientists discovered that B cells in the marginal zone of the spleen are the first lymphocytes to act in the body after infection, rapidly producing antibodies that prevent the virus from spreading and reaching the central nervous system and brain. This early production of antibodies depends on a protein, MyD88, which activates the response, helping to neutralize Oropouche.

The results of the study are published in the journal eBioMedicine, from the Lancet group (United Kingdom).

“This study yielded a very important result, advancing our understanding of how this virus acts in two ways. First, from a mechanistic perspective, by analyzing the marginal zone B lymphocyte pathway, which has been little explored in relation to arthropod-borne viral infections. This helps us understand the mechanisms associated with encephalitis and those that protect the body from viral access to the central nervous system,” explains José Luiz Proença Modena, one of the study’s advisors and a professor at the Institute of Biology at the State University of Campinas (IB-UNICAMP) in Brazil. “The second point is related to the possibility of therapy and vaccines, showing that antibodies act quickly. This suggests that the therapeutic window may not be so long, requiring rapid action in the early stages of infection.”

Modena is the coordinator of the Laboratory of Emerging Viruses (LEVE) at UNICAMP. LEVE is supported by FAPESP, which also funded the research through three other projects (16/00194-8, 17/11931-6, and 14/50938-8).

The lead author of the article, researcher Daniel Teixeira, points out that the threat of outbreaks and epidemics makes understanding the mechanisms of Oropouche infection even more urgent. “We’ve managed to shed light on a virus that’s still little known to the general public. By studying it, it’s possible to predict processes that may be triggered in the body, and as a result, science can prepare to face epidemics.”

Earlier this year, another study published in the journal Infectious Diseases – also involving scientists from LEVE – showed that Oropouche fever, documented in South America since the 1950s, experienced an explosion of cases between November 2023 and June 2024 in four countries: Brazil, Bolivia, Colombia, and Peru.

In Brazil, autochthonous infections were recorded in areas that were previously non-endemic in all five of the country’s regions, with cases in 21 states. The incidence rate increased almost 200-fold compared to the last ten years. “The symptoms of the disease are similar to dengue and Zika and can be confused. Therefore, tests for Oropouche are also necessary for epidemiological monitoring,” Modena adds.

Following the increase in cases, the Ministry of Health updated the rules for surveillance and control of the Oropouche virus in Brazil, which is now subject to mandatory reporting – that is, all suspected or confirmed cases must be reported within 24 hours.

Partnership

The work was carried out by a group of 30 researchers from various institutions. In addition to UNICAMP, the group included scientists from the University of São Paulo (USP), the Federal University of Roraima, and FIOCRUZ Amazônia (also in Brazil), Cardiff University (United Kingdom), the University of Kentucky, and Washington University in St. Louis (United States).

“We benefited from the efforts of foreign researchers, but most of the work – the actual hands-on work – was done in Brazil by graduate students. This shows the importance of investing in science and in training new scientists,” Teixeira points out.

The group conducted immunophenotyping experiments, passive serum transfers, and adoptive cell transfers to determine how early antibody and B cell responses control viral replication and spread to the central nervous system after infection. The mice produced specific antibodies against OROV within six days of infection.

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 www.fapesp.br/en and visit FAPESP news agency at 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.