Sabiavirus causes acute hemorrhagic neurological syndrome. Four deaths have been recorded in São Paulo state since 1990. This virus has been circulating in Brazil for about 142 years. Genome analysis of two cases recorded in 2019 and 2020 shows that the virus undergoes genetic changes over time, explaining why existing tests were not able to identify the virus.
These results are part of a study published in the journal Tropical diseases ignored by PLOS. The study was supported by FAPESP and carried out by researchers from the Brazil-UK Collaborative Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE), a research center based at the University of São Paulo Faculty of Medicine (FM-USP) and Imperial College London, UK.
“The reference strain of the Sabia virus dates back to a case that occurred in Cotia in 1990. The diagnostic method was developed based on its genome. Since more than 30 years have passed, it was very likely that the virus had mutated. Although we do not have enough cases to further test this method, it can be used in future suspected cases with a higher accuracy than the tests used so far,” says Ingla Morales Claro, who conducted the research during her doctoral studies. He received a FAPESP scholarship to study at FM-USP and is currently pursuing postdoctoral research at the University of Kentucky in the United States.
The research team developed primers – small DNA fragments used to detect the virus in clinical tests – and sent them to the Adolfo Lutz Institute in São Paulo, one of the state’s leading facilities for this kind of testing.
The genome recovered from Sabia was approximately 89% genetically identical to a strain previously reported in 1999, when the second-ever case was recorded. “When we analyzed the genomes of the new cases, we identified mutations in the target regions of the primers that prevented existing diagnostic tests from detecting them. By correcting these regions, we were able to identify the strains that are now prevalent,” Claro explained.
CADDE is coordinated in Brazil by FM-USP Professor Estelle Sabino, who led the sequencing of the country’s first SARS-CoV-2 in March 2020 and the mpox virus in 2022 (For more information, visit agencia.fapesp.br/32656/, agencia.fapesp.br/35414/, and agencia.fapesp.br/38928.). In the UK, the center is coordinated by Nuno Faria at Imperial College London.
His team led the ZiBRA project, which sequenced the Zika virus and mapped yellow fever outbreaks in Brazil and São Paulo. Together with Sabino, his team also coordinated the initial characterization of the SARS-CoV-2 gamma variant in Manaus (For more information, see revistapesquisa.fapesp.br/en/breaking-boundaries/ and agencia.fapesp.br/35449.).
How viruses interact with human cells
The 2020 Sabia virus infection cases were identified through metagenomic analysis, a technique that detects a variety of microorganisms in a sample without knowing which viruses to test for in advance. The virus was present in the blood of a 52-year-old patient from Sorocaba. A rapid metagenomic approach developed during Claro’s doctoral research was used to detect emerging pathogens in clinical samples.
The man had a history of hiking in forested areas and sought treatment at a primary care clinic on December 30, 2019. He was then transported to the FM-USP General Hospital and Teaching Hospital (Hospital) in São Paulo on suspicion of yellow fever, where he died on January 11, 2020. Initial tests were negative for yellow fever and Sabia virus.
After subsequent tests detected the virus, researchers analyzed blood samples from seven previous patients with acute hemorrhagic neurological syndrome who had tested negative for yellow fever. They discovered a case related to a 63-year-old rural worker from Asis who was admitted to Hospital Das Clinic on December 10, 2019 and died two days later.
In both cases, the researchers observed changes in proteins that allow the virus to bind to human cells. Phylogenetic analysis, which allows reconstruction of the virus’s evolutionary history, shows that the pathogen has been circulating in Brazil for decades and is likely not a recent introduction.
There may have been other unconfirmed incidents in the past. It is important to understand the virus, develop tests, and study the changes occurring in its genome so that we can predict future cases of the disease, and even epidemics. ”
Esther Sabino, FM-USP Professor
The species that harbors the virus is still unknown, but it is believed to be a wild rodent. Infections occurred in rural areas where wildlife and humans may come into contact.
“In this context, metagenomic approaches have proven to be an essential tool for detecting rare or unexpected pathogens, especially when targeted diagnostic tests have failed. “This study is fundamental in identifying fatal cases of yellow fever and highlights the important role of genomic surveillance in detecting public health risks,” Faria said, citing as an example the group’s recent work on the evolution and transmission dynamics of yellow fever in Brazil.
Sabiavirus is considered one of the Brazilian viruses with the highest risk of aerosol transmission in laboratory settings. Handling this requires the highest level of biosafety, and this capability does not yet exist in South America.
Japan’s first laboratory capable of storing and handling the active virus Orion is scheduled to open in 2030. The institute is currently under construction at the Brazilian Center for Energy and Materials Research (CNPEM) in Campinas. Currently, the Sabia reference stock is stored in the United States (For more information, please visit agencia.fapesp.br/52207.).
sauce:
São Paulo Research Foundation (FAPESP)
Reference magazines:
Claro, Im others. (2026). Genomic characterization of Sabiavirus in Brazil, 2019-2020: Implications for diagnosis, virus evolution, and receptor binding. PLOS is a neglected tropical disease. DOI: 10.1371/journal.pntd.0014008. https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014008
