Genetic factors may determine severity of hantavirus infection

The results of a study conducted in Brazil were presented in the city of Lubbock, United States, during FAPESP Week Nebraska-Texas.

By Karina Toledo, in Lubbock (USA)  |  Agência FAPESP – Characterized by rapidly evolving severe pneumonia, hantavirus cardiopulmonary syndrome (HCPS) is a viral disease transmitted primarily by wild rodents.

Although the lethality rate for HCPS is over 40%, not everyone who comes in contact with the pathogen develops symptoms. According to results from a study conducted at the Ribeirão Preto School of Medicine (FMRP) of the University of São Paulo (USP) in Brazil, the explanation may be related to genetic factors.

The subject was discussed by Professor Luiz Tadeu Moraes Figueiredo during FAPESP Week Nebraska-Texas, held on September 18-22 in the cities of Lincoln, Nebraska and Lubbock, Texas.

The FMRP-USP group compared genetic data of 27 people who developed HCPS with that of 90 people who never manifested the disease, despite having positive results in serological tests for hantavirus (in other words, their blood contained antibodies against the virus).

In the fatal cases, the researchers observed increased frequency of the presence of a particular variation in the gene that encodes the tumor necrosis factor-alpha (TNF-α). That polymorphism known as TNF-α-308 had already been associated in studies of other groups of autoimmune diseases.

In the asymptomatic patients, however, the group noted greater expression of the transforming growth factor-beta (TGB-β), which encodes a cytokine capable of inhibiting the inflammatory response.

“We studied some fatal cases and observed that the virus is found in the myocardium, along with numerous other inflammatory molecules – which could explain the occurrence of shock [when the heart loses its ability to properly pump blood]. There seems to be a cytokine storm that leads to very intense inflammation and the regulation of that immune response is inhibited,” Figueiredo explained.

In his presentation, the researcher reported that hantavirus originated in Asia and likely arrived in the Americas some 500 years ago. The main reservoirs of the pathogen in Brazil are small terrestrial mammals, particularly wild rodents. However, Figueiredo’s team has also managed to isolate the virus in bats.

“We do not yet know, however, if bats are capable of transmitting the disease to humans,” he said.

As the researcher explained, contamination occurs by breathing in dust contaminated by the urine, saliva or feces of infected animals. The disease can also be contracted from the bite of a rat, consuming contaminated water and food or handling infected rodents in a laboratory.

In Brazil, those mainly affected are rural workers. The Brazilian Ministry of Health recognizes the occurrence of nearly 2,000 cases of HCPS and slightly over 700 deaths from the disease. The regions with the most number of cases are in the south of Brazil – primarily the states of Santa Catarina, Paraná and Rio Grande do Sul –, northeastern São Paulo, the western region of Minas Gerais State known as the Triângulo Mineiro and Brazil’s Central Plateau.

There are just a few centers in Brazil that have the structure to study such a virulent microorganism, among them the Center for Research in Virology at FMRP-USP, which built a Biosafety Level 3 laboratory (the second safest on the scale) with funding from FAPESP.

In 2006, the researchers filed a patent application for an antigenic protein of hantavirus – which causes the formation of specific antibodies when introduced into the body – produced at the center. The protein is currently being used to diagnose the disease but the idea is to use it to create a vaccine.

Zika

The most recent scientific findings about the Zika virus in Brazil – including those from a study of 55 women confirmed to have the Zika virus during pregnancy – were presented by Maurício Lacerda Nogueira, a professor at the São José do Rio Preto School of Medicine (FAMERP), in the State of São Paulo.

Unlike what was observed among pregnant women infected with the virus in the Northeast Region of Brazil or in Rio de Janeiro, all the women tracked in São José do Rio Preto carried the pregnancy to term. The babies were born alive and not a single case of microcephaly or any other serious neurological alteration was identified (read more about this at: agencia.fapesp.br/25511).

According to Nogueira, it was initially thought that a possible explanation for the occurrence of more severe cases of Zika in the Northeast and Rio de Janeiro was the fact that most of the population of those locations had already had previous contact with the dengue virus.

Previous studies, using only cells and rodents, had in fact suggested that prior infection by dengue could potentially aggravate Zika infection by facilitating multiplication of the virus.

“But that is not what we observed in our population, which also lives in an area where dengue is endemic. In individuals whose serological tests presented positive results for dengue as well as Zika, there was no increase in either the viral load or inflammatory cytokines in the blood, nor were there more serious manifestations as observed in those suffering from secondary dengue infection,” Nogueira told the Agência FAPESP (read more about this at: agencia.fapesp.br/25572).

Since 2015, with funding from FAPESP, the group from FAMERP has been monitoring a group of 1,000 people from the population of São José do Rio Preto. The most recent results were published in the journal Clinical Infectious Diseases.

“Initially, that result is very positive, as it suggests that the dengue vaccine will not increase the risk of severe manifestations of the Zika virus. But in order to be certain, those individuals need to have long-term monitoring. In the case of dengue at least, we know that the time difference between the first and second infection influences the severity of the symptoms,” Nogueira told the Agência FAPESP.

According to Nogueira, the worst cases appear when the second dengue infection occurs between 9 and 18 months after initial contact with the virus.

Also during the symposium in the United States, Steve Presley, a professor at the Institute of Environmental and Human Health at Texas Tech University (TTU) announced that the state of Texas is tracking whether mosquitos of the species Aedes albopictus and Aedes aegypti are becoming resistant to the insecticides widely used in the region.

“In the event of an outbreak of chikungunya or Zika, we need to be certain that we are using the correct product to control the vector,” Presley said.

Professor Jorge Salazar-Bravo, of the Department of Biological Sciences of TTU, talked about the importance of knowing the biology behind the zoonoses, in other words, how the interactions among the various pathogens and their hosts occur. This knowledge, he says, can predict where newly emerging diseases may arise.