10/13/2025 | Camila Neumam | Butantan Institute

https://butantan.gov.br/noticias/pesquisa-do-butantan-define-nova-nomenclatura-de-linhagens-do-virus-da-dengue-para-otimizar-vigilancia-genomica 

A study conducted in partnership with 23 other institutions, including Yale University in the US, expands classification beyond genotypes, demonstrating continuous mutations of the virus

A study conducted by researchers at the Center for Viral Surveillance and Serological Evaluation (CeVIVAS) at the Butantan Institute, in conjunction with 23 other institutions, including Yale University in the United States, defines a new nomenclature system for dengue virus (DENV) strains to complement genotype classification. 

The goal is to facilitate genomic surveillance, that is, to promote communication between laboratories and health authorities, making strain tracking more accurate and comparable, in addition to monitoring potential strains with epidemiological or clinical relevance. 

The research, entitled A new lineage nomenclature to aid genomic surveillance of dengue virus, was published in the scientific journal PLOS Biology.

Bioinformaticians Alex Ranieri and James Siqueira, from CeVIVAS, developed, in conjunction with 23 institutions, a new nomenclature system for dengue virus lineages.

"From an epidemiological point of view, the dengue that circulates is the same as it has been for the last 20 years, and it seems that the virus is not changing, when in fact it is. The new nomenclature classifies the virus systematically, making it easier to identify and allowing any researcher to classify these samples," says Alex Ranieri, a bioinformatician at CeVIVAS and the Butantan Cell Cycle Laboratory (LCC) and one of the study's lead authors.

Dengue is a viral disease transmitted by the Aedes aegypti mosquito, which puts more than 100 million people at risk each year worldwide, according to the World Health Organization (WHO), especially in tropical countries such as Brazil. 

To date, four serotypes of the dengue virus have been identified: DENV-1, DENV-2, DENV-3, and DENV-4. Within each serotype, there are different genetic variations, called genotypes. Over time, these viruses accumulate mutations in their genetic material (RNA) and give rise to lineages, which represent more recent or older branches in the evolutionary history of the virus.

In other words: we first distinguish dengue viruses by serotype, which can be divided into different genotypes. In the new dengue virus nomenclature scheme, genotypes are indicated by Roman numerals (e.g., genotype III), and within them there are two hierarchical levels: the larger lineages represented by letters (e.g., DENV-3III_C), and the smaller lineages indicated by numbers separated by dots (e.g., DENV-3III_C.2). . This system can be expanded as needed, generating sublineages such as DENV-3III_C.2.1, similar to the scheme used for SARS-CoV-2 (the virus that causes Covid-19). Thus, each name carries evolutionary and epidemiological information, allowing for clear identification of the relationship between different viral groups.

“There was no standardized way to classify what was below the genotype, making it difficult to analyze the variety of the virus at this level and to communicate scientific and epidemiological information to public health authorities,” says bioinformatician James Siqueira Pereira, a doctoral student affiliated with the Butantan Institute's Higher School (ESIB) and the Interunit Bioinformatics Program at the University of São Paulo (USP) under the guidance of Alex Ranieri.

In 2024, countries in the Americas, where the four dengue serotypes circulate, reported more than 13 million cases; of these, almost 7 million were confirmed in the laboratory. Brazil was the country with the highest number of cases (10.2 million), followed by Argentina (581,500), Mexico (558,800), Colombia (321,000), and Paraguay (295,700), according to the Pan American Health Organization (PAHO).

How the new nomenclature came about
The nomenclature of the lineages was defined taking into account the principles of Phylogenetic Assignment of Named Global Outbreak Lineages (Pango lineages), a hierarchical system created to track the evolution of SARS-CoV-2 variants; as well as the logic of older systems, such as the one used to name influenza viruses.
 

The research methodology was based on the analysis of a vast database of DENV genomic sequences, many of which were generated by the CeVIVAS project. The lineages were defined using high thresholds for phylogenetic distance (branches that indicate different mutations of the virus) [SEE INFOGRAPHIC] and clade size, which are groups of sequences that share a common ancestor and its descendants. 

The system was implemented in lineage assignment tools such as Genome Detective, GLUE, and NextClade, which are capable of performing classification even with partial sequences.

“By making the system compatible with existing classifications and demonstrating its usefulness, we aim to achieve widespread acceptance and introduce a truly standardized global language for discussing the genetic diversity of DENV,” says James Siqueira.

The system was applied to samples of dengue viruses circulating in various geographical locations, demonstrating the temporal tracking of lineages of the four serotypes in a global context.

"NextClade, one of the tools where the system was implemented, is capable of quickly and easily analyzing a large number of sequences and can be used by people with and without experience in bioinformatics. In addition, to keep everything within the norms, there is a committee that meets and reviews the sequences, assesses whether there are any discrepancies, and monitors strains with a high possibility of being new," says James Siqueira.

By enabling the classification of lineages even with partial genomic coverage, the system becomes a practical tool in scenarios with limited data. In addition, it has also proven useful for vaccine development, transmission studies, and potential virulence.

“This work presents a robust proposal to standardize the tracking of dengue virus lineages, with accurate public tools, even with incomplete data. The hierarchical nomenclature of lineages (major/minor) promises to improve global surveillance of the dengue virus,” emphasizes Alex Ranieri.

According to the researchers, the new classification gains importance in light of the spread of dengue in Brazil and worldwide, especially in non-endemic areas such as the United States and Europe, while global sequencing capacity also expands through integration with public health systems.

“The idea is to facilitate and provide tools for epidemiologists and public health decision-makers, so that they have a systematic way of defining what is circulating now, comparing it with what was circulating previously, and the implications of this,” explains Alex Ranieri.

Spread of dengue requires greater surveillance
The four DENV serotypes and their genotypes were identified in the late 1990s and early 2000s based on partial genetic sequences. 

Although they all cause the same disease, infection with one of the four serotypes confers immunity only to that specific virus, not to the other three serotypes. On the contrary, subsequent infections with other serotypes increase the chance of more severe forms of the disease, such as severe dengue, which for a long time was known as dengue hemorrhagic fever.

According to the Ministry of Health, the first clinically and laboratory-documented dengue epidemic in Brazil occurred in the early 1980s in Boa Vista (RR), caused by serotypes 1 and 4. In 1986, epidemics occurred in the state of Rio de Janeiro and in some capitals in the Northeast. 

Since then, the occurrence of the endemic form of the disease has been interspersed with years of epidemics, usually associated with the introduction of new serotypes in areas without transmission and/or changes in the predominant serotype, accompanying the expansion of the mosquito vector.

According to the Ministry of Health's Arbovirus Monitoring Panel, the increase in the incidence of dengue in Brazil between 2000 and 2002 was associated with the introduction of DENV-3, increasing the risk of epidemics of dengue and dengue hemorrhagic fever. In 2024, the country experienced a large increase in the number of cases of the disease caused by the reintroduction of this serotype, with more than 6.5 million probable cases and more than 6,300 deaths reported. 

"The continuous evolution and spread of the dengue virus has led to the emergence of distinct evolutionary lineages within recognized genotypes. In addition, with the implementation of interventions such as vaccines and infected mosquitoes that may eventually select specific viral lineages, it is imperative to have a precise and common language to monitor the continuous transmission of dengue at different spatial and temporal scales, and that this be communicable to physicians and public health authorities who may not have experience in genomics," concludes Alex Ranieri.