Scientists have uncovered new clues about the evolution of a rare, deadly Brazilian virus that has circulated largely undetected for more than a century.
A rare and deadly virus went undetected in Brazil after genetic changes allowed it to escape existing laboratory tests. Scientists investigating two fatal infections have now identified the mutations responsible, developed an improved detection method, and uncovered evidence that the pathogen has circulated in the country for more than a century.
The Sabiá virus can cause severe hemorrhagic and neurological illness, yet only four fatal cases have been documented in São Paulo state since 1990. New genomic research, published in PLOS Neglected Tropical Diseases, suggests that additional infections may have escaped diagnosis.
Why Existing Tests Failed to Detect the Virus
The investigation focused on two infections identified in 2019 and 2020. Researchers recovered viral genomes that were approximately 89% genetically identical to strains described in 1999. Crucially, some mutations affected the regions recognized by the DNA primers used in diagnostic tests, preventing those tests from detecting the circulating virus.
“The reference strain of the Sabiá virus dates back to 1990, from a case in Cotia. The diagnostic method was developed based on that genome. Since more than 30 years have passed, it was very likely that the virus had mutated. We don’t have enough cases to validate this method further, but it can be used for future suspected cases with greater accuracy than the tests used until now,” says Ingra Morales Claro, who conducted the research during her doctoral studies at the University of São Paulo Medical School (FM-USP) with a FAPESP scholarship. She is now a postdoctoral researcher at the University of Kentucky.
“When analyzing the genomes of the new cases, we identified mutations in target regions of the primers that prevented detection by existing diagnostic tests. We modified those regions, and now it’s possible to identify the circulating strains,” Claro explains. The redesigned primers have been sent to the Adolpho Lutz Institute, a major public health laboratory in São Paulo.
Two Fatal Infections Uncovered Through Genetic Analysis
One case involved a 52-year-old man from Sorocaba who had a history of hiking in forested areas. He sought medical attention on December 30, 2019, and was transferred to the Hospital das Clínicas (Hospital das Clínicas) in São Paulo with suspected yellow fever. Initial tests for yellow fever and Sabiá virus were negative, and he died on January 11, 2020.
Researchers eventually detected Sabiá virus in his blood using metagenomic analysis, which searches for genetic material from multiple microorganisms without requiring scientists to identify a particular pathogen in advance. The rapid approach had been developed during Claro’s doctoral research to detect emerging pathogens in clinical samples.
The discovery prompted the team to examine blood samples from seven earlier patients with acute hemorrhagic and neurological illness who had tested negative for yellow fever. One sample revealed another Sabiá infection in a 63-year-old rural worker from Assis. He had been admitted to the Hospital das Clínicas on December 10, 2019, and died two days later.
Genetic Evidence Points to a Much Older Virus
Analysis of the newly recovered genomes identified changes in a viral protein involved in binding to human cells. Although these alterations could be relevant to how the virus interacts with its hosts, the study did not establish whether they changed its ability to infect people or cause severe disease.
The researchers also reconstructed the virus’s evolutionary history using phylogenetic analysis, which compares genetic differences to estimate relationships between viral lineages. Their findings suggest that Sabiá has been circulating in Brazil for approximately 142 years, rather than representing a recent introduction.
“There were likely other cases in the past that went unidentified. It’s important to understand the virus, develop tests, and study the changes occurring in its genome so that we can anticipate future cases, and even outbreaks, of the disease,” warns Ester Sabino, a professor at FM-USP who coordinates the Brazil-UK Joint Center for Arbovirus Discovery, Diagnostics, Genomics, and Epidemiology (CADDE) in Brazil.
The Unknown Animal Reservoir
Scientists have not established which animal species naturally maintains Sabiá virus, although wild rodents are considered possible reservoirs. The known infections occurred in rural settings where people may encounter wildlife, but the precise route of transmission remains uncertain.
The investigation was carried out by CADDE researchers affiliated with FM-USP and Imperial College London, with support from FAPESP. The center has also contributed to genomic investigations of SARS-CoV-2, Zika, mpox, and yellow fever. Sabino helped lead Brazil’s first sequencing of SARS-CoV-2 in March 2020 and subsequent sequencing of mpox in 2022. Nuno Faria, who coordinates CADDE’s UK team, has worked on genomic surveillance of Zika, yellow fever, and the SARS-CoV-2 Gamma variant.
“In this context, metagenomic approaches have proven to be essential tools for detecting rare or unexpected pathogens, especially when targeted diagnostic tests fail. This strategy was fundamental in identifying both fatal cases of Sabiá in humans and in wild animals, and it highlights the essential role of genomic surveillance in detecting public health risks,” says Faria, referring also to the group’s research on yellow fever evolution and transmission in Brazil.
A Major Challenge for Future Research
Studying Sabiá virus presents unusual laboratory safety challenges. It is considered one of the Brazilian viruses with the greatest risk of transmission through infectious aerosols in laboratory settings. Handling the active virus requires the highest level of biosafety containment, which is not currently available in South America.
Brazil plans to address that limitation with Orion, a laboratory being built at the Brazilian Center for Research in Energy and Materials (CNPEM) in Campinas. Scheduled to open in 2030, it will be the country’s first facility equipped to store and handle active Sabiá virus. The reference strain is currently held in the United States.
Reference: “Genomic characterization of Sabiá virus in Brazil, 2019–2020: Implications for diagnostics, virus evolution, and receptor binding” by Ingra M. Claro, Erika R. Manuli, Camila A. M. da Silva, Thaís M. Coletti, Philippe Lemey, Ana Catharina Nastri, Luciana Vilas Boas Casadio, Amaro Nunes Duarte-Neto, Joshua Quick, Camila M. Romano, Charles Whittaker, Sarah C. Hill, Carlos A. Prete, Darlan S. Candido, Filipe R. R. Moreira, Mariana S. Ramundo, Ian Nunes Valença, Jaqueline G. de Jesus, Flavia C. S. Sales, Mariana S. Cunha, Juliana M. Guerra, Maria Cassia Mendes-Correa, Tania R. Tozetto-Mendoza, Marcilio Jorge Fumagalli, Yeh-Li Ho, Peter Simmonds, Weng M. Ng, Thomas A. Bowden, William M. de Souza, Oliver G. Pybus, Anna S. Levin, Nicholas Loman, Ester C. Sabino and Nuno R. Faria, 20 February 2026, PLOS Neglected Tropical Diseases.
DOI: 10.1371/journal.pntd.0014008
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