# Genomic characterization of Sabiá virus in Brazil, 2019–2020: Implications for diagnostics, virus evolution, and receptor binding

## TL;DR

Researchers identified and analyzed two new cases of Sabiá virus in Brazil, highlighting the need for improved diagnostics and surveillance for this deadly virus.

## Contribution

The study provides the first genomic characterization of the third and fourth naturally acquired Sabiá virus cases and develops new molecular tests for detection.

## Key findings

- The new Sabiá virus cases were genetically distinct from previous strains, with 93-98.2% amino acid identity at the NP level.
- Phylogenetic analysis suggests SABV has been circulating in Brazil for over a century without detection.
- The study reveals insights into SABV receptor binding, showing structural similarities to other clade B arenaviruses despite amino acid variation.

## Abstract

Between December 2019 and January 2020, two patients suspected of having severe yellow fever were admitted to a tertiary healthcare facility in São Paulo, Brazil, presenting with acute hemorrhagic syndrome and neurological alterations; both cases had fatal outcomes. Upon admission, both tested negative for yellow fever viral RNA, and Sabiá virus (SABV), a New World arenavirus, was identified as the causative pathogen. To date, only four humans naturally acquired SABV infections have been confirmed, all fatal and linked to rural settings. We applied next-generation sequencing to generate complete and near-complete genomes from two patients (SP17 and SP19). Existing molecular diagnostics failed to detect SABV; therefore, new molecular tests were developed. Genetic analyses of SP17 and SP19 genomes along with other arenaviruses, revealed that the new cases were genetically diverse, showing 93-98.2% amino acid identity at the NP level among SP17, SP19, and the 1990 reference strain (SPH114202). Time-scaled phylogenetic analyses confirmed that SP17 and SP19 were not epidemiologically linked and suggested that SABV has been circulating undetected in Brazil for over a century. Additionally, homology modeling and structure-based mapping provided insights into SABV receptor-binding sequence conservation, suggesting that SABV shares similar receptor binding structure to other clade B arenaviruses, despite some amino acid variation around receptor binding site. Our findings underscore the need for retrospective and prospective surveillance of undiagnosed hemorrhagic fever cases to assess the public health impact of SABV in Brazil.

Sabiá virus (SABV), also known as Brazilian mammarenavirus, causes severe hemorrhagic fever, with mortality rates among New World arenaviruses averaging around 30%. Over the past 40 years, four naturally acquired cases have been confirmed in Brazil, all fatal and linked to rural settings. Here, we characterized the genomic features of the third and fourth naturally acquired cases, identified in 2019 and 2020 in São Paulo, Brazil, in patients initially suspected of yellow fever. These cases were detected using untargeted metagenomic sequencing in a São Paulo healthcare facility. Our findings reveal that existing molecular diagnostics failed to detect contemporary SABV strains, leading to the development of novel assays based on newly generated SABV genomes. Genetic analyses confirm that these cases were not epidemiologically linked and provide evidence of SABV circulation in Brazil for over a century. Additionally, we present new insights into SABV receptor interactions, improving our understanding of its tropism. These findings expand the limited knowledge of SABV epidemiology and genetic diversity, with direct implications for diagnostics, surveillance, and outbreak preparedness against this highly pathogenic virus. Greater efforts should focus on pathogen-agnostic investigations of hemorrhagic fever cases, particularly in patients who test negative for yellow fever. Expanded surveillance is essential to better understand the disease spectrum, pathogenicity, transmissibility, and zoonotic reservoir of SABV.