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Two new viruses are identified in patients with suspected dengue fever

Publicado em 11 março 2020

Two new virus species have been identified in the blood of patients with symptoms similar to dengue or Zika, such as fever, headache and reddish patches on the skin. One of the microorganisms belongs to the genus Ambidensovirus and was found in a sample collected in Amapá. The other, present in a sample from Tocantins, belongs to the genus Chapparvovirus. The results of the research, supported by FAPESP, were published in the journal PLOS ONE.

“What surprised us the most was to find an Ambidensovirus in a human sample. Species of this genus had only been described in insects, crustaceans and other invertebrates. Never in mammals,” said Antonio Charlys da Costa, postdoctoral fellow at the University of São Paulo Medical School. São Paulo (FM-USP) and one of the authors of the study.

According to the researcher, different species of Chapparvovirus had already been described in mammals, but never in humans. “It is not yet possible, however, to know if these microorganisms were active in the organism or if they were the cause of the symptoms”, Costa told Agência FAPESP.

In the evaluation of Eric Delwart, a researcher at the Vitalant Research Institute (United States) and project supervisor, other scientists will be able, from these results, to investigate whether the new viruses are present in other people in the region or in other populations, as well as if there are risk of dissemination.

“So far, there is no evidence that these viruses have spread or that they are pathogenic. But it is scientifically interesting to find an Ambidensovirus in human hosts. This discovery reflects how little we know about the ability of the little-studied viruses to infect different cell types, “said Delwart.

The researcher also stressed the importance of reusing pre-existing clinical samples in research aimed at the surveillance of potentially emerging viruses. In the case of this study, the samples analyzed were originally collected by Central Public Health Laboratories (Lacens) from different States, in routine care.

Viral diversity

The identification of the new species was possible thanks to a technique known as metagenomics, which allows the simultaneous sequencing of all genetic material – from various organisms – contained in a sample of blood, urine, feces or saliva. Through this method it is also possible, for example, to study all soil bacteria and fungi in a region or to map the different species that make up an individual’s intestinal microbiota.

After all the nucleic acids in the sample are extracted and sequenced, the researchers use bioinformatics tools to compare the results with already known genomic sequences, described in databases.

Costa learned the methodology while at the doctorate, during an internship at Delwart’s laboratory. In Brazil, the research supervisor was a professor at FM-USP Ester Sabino, former director of the Institute of Tropical Medicine (IMT-USP).

The article describes the analysis of 781 samples collected between 2013 and 2016. In 80% of them, the presence of the genus was identified Anellovirus (without assigned disease), 19% contained HPgV-1 (known as Pegivirus Type 1 human and also without related disease) and 17% tested positive for parvovirus B19, which causes infectious erythema, common in children, characterized by mild fever and red rash on the face, arms, legs and trunk.

Only in two samples were viral species never found before, both belonging to the family Parvoviridae.

The material was given to researchers by the Lacens of Amapá, Tocantins, Paraíba, Maranhão, Mato Grosso do Sul, Piauí and Maranhão.

“The study continues and, in all, we have already received more than 20 thousand samples for analysis. They pass on those that are negative for the presence of dengue, zika and chikungunya. In our laboratory, at the Instituto de Medicina Tropical, we do molecular tests for detect others Flavivirus [os causadores da febre amarela e da febre do Nilo Ocidental, por exemplo], Alphavirus [gênero que inclui o mayaro e várias espécies causadoras de encefalite] and Enterovirus [que podem causar doenças respiratórias e síndrome da mão-pé-boca, entre outros quadros] already known. When we didn’t find anything, we started the metagenomic analysis “, explained Costa.

According to the researcher, the objective of the project is to describe the viral diversity that exists in Brazil and to identify species that may be causing disease in humans and go unnoticed amid outbreaks of arboviruses.

A study published in the journal Clinical Infectious Diseases in 2019, for example, described the occurrence of an outbreak of parvovirus B19 amid a dengue epidemic between 2013 and 2014. The investigation was coordinated by USP researcher Paolo Zanotto, with support from FAPESP.

“This is a case of relevance to public health, because if it infects pregnant women, parvovirus B19 can cause serious problems in the fetus,” said Costa.

Next steps

To find out if the two new viral species described pose a risk to human health, further, more detailed studies will be needed.

“We tried to infect cell cultures in the laboratory, but it was not possible. We do not know if it is because these viruses do not infect the type of cell we used in the experiment or if the viral particles contained in the samples we analyzed were no longer viable,” said Costa.

However, the group obtained a second sample of the virus identified in the Tocantins patient (Chapparvovirus) and is now working on the development of a serological test. “The idea is to find out if this patient and his family have antibodies against this microorganism, which would indicate that they have been infected in the past and have produced a response against the microorganism,” he said.

The research was also supported by FAPESP through the project “Viral metagenomics of dengue, chikungunya and zika virus: to monitor, explain and predict the space-time transmission and distribution in Brazil”, coordinated by Sabino.