A previous infection by dengue exerts a protective effect against the Zika virus and its effects on pregnancy, according to a study carried out by scientists from La Jolla Institute (LJI) for Allergy and Immunology.

The paper, published in Nature Communications, document that dengue immunity caused by previous infection protects pregnant women from the effects of Zika infection. José Ángel Regla Nava, first author of the paper, is a Mexican scientist who is doing a postdoctoral fellowship in virology and immunology at LJI. His research is supervised by Sujan Shresta, leader in mosquito-borne diseases such as dengue and Zika.

Zika virus infection during pregnancy represents a significant risk: when the infectious agent crosses the placental barrier, it can cause intrauterine growth restriction, spontaneous abortion, microcephaly and other congenital defects. However, not all pregnant women exposed to Zika in regions where dengue is also found show these problems in their pregnancy, but why?

Dengue and Zika viruses are “close relatives” because both belong to the family of flaviviruses and are transmitted by the bite of the Aedes aegypti mosquito. In addition, they share more than 50 percent of their DNA sequence, said Regla Nava in an interview with the Information Agency of the National Council for Science and Technology (CONACYT).

In a previous investigation, Regla Nava and collaborators documented that adult mice infected with dengue were immune to Zika; from there, the next step was to understand if the immunity effect observed also happened in pregnant mice.

Regla Nava explained that mice are not susceptible to Zika virus, therefore animal models deficient in type I interferon were used, as this cytokine plays an important role in antiviral defense, stopping the infection.  The researchers infected virgin females of this animal model with dengue virus one month before they were exposed to Zika virus. The exposition to Zika was carried out during pregnancy at an early embryonic stage, seven days of gestation (which in humans would be the first trimester of pregnancy) to know whether immunity to dengue protected mothers and their fetuses from Zika infection.

The results showed that the dengue-immune mice exposed to Zika virus had a normal size and appearance, while the animals that were not infected by dengue, and thus were not immune, had fetal death.

Here we see that dengue virus generates a kind of protection in pregnant mice,” said Regla Nava.

This protection appears to be conferred by the immunity of CD8 T cells. These cells, also known as cytotoxic T lymphocytes, are an important tool against intracellular pathogens, such as bacteria or viruses.

We investigated how this mechanism of protection of CD8 T cells is carried out. We really do not know if they limit the transmission or have a greater function in the defense,” explained Regla Nava.

The researchers eliminated the response of CD8 T cells in pregnant mice, while in another group of animals they did not. When comparing the results, the scientists observed that the fetuses of the pregnant mice with no CD8 T cell response had an abortion; whereas in the other group, the fetuses did not show abnormal changes.

CD8 T cells are important for this immunity. The mice that were not immunized had a high viral load, which decreased in the opposite case,” shared doctor José Regla Nava.

The researchers not only studied the viral load of the mother, but also that of the fetus and the results were similar. They also emulated a method of vaccination with peptides that induced the response mechanism of CD8 T cells.

Days after vaccination, the researchers measured levels of viral RNA and observed that they decreased significantly in the placenta of the immunized mice, but not in the mice that did not received the ‘vaccine’.

CD8 cytotoxic T cells caused by dengue infection remained present in the placenta of pregnant mice infected with Zika, suggesting a line of defense against transmission through the placenta,” said a statement issued by the Institute La Jolla for Allergy and Immunology.

The protection period in mice is short, so researchers are now working on ways to increase this immunity. According to Regla Nava, this finding has important implications for understanding the natural history of the Zika virus, as well as opening the possibility to create vaccines against the disease.

Currently, most of the vaccines under develop to combat the Zika infection are aimed at promoting an antibody response. But a vaccine that induces a CD8 T cell response, in addition to the antibody response, may confer greater protection against Zika virus, said Regla Nava.

Zika and neurodegenerative diseases

Dr. José Ángel Regla Nava is also focused on understanding the effects of Zika infection in adult mice.

Almost all of the research that has been reported for Zika disease involves pregnant women, but we have seen that the infection also affects the brains of adult mice. Results of this research were published in the journal Cell Stem Cell,” said Regla Nava.

Regla Nava and colleagues studied the brains of adult mice infected with the Zika virus. The results: it affected neurons. “This allows us to assume that infection by this virus in adults could cause a defect in memory,” he explained.

Future plans

After completing his postdoctoral studies, the goal of Dr. José Ángel Regla Nava is to return to Mexico and establish a laboratory focused on the study of emerging diseases caused by vectors, such as dengue and zika, and other emerging diseases such as SARS virus, a subject he worked during his master’s and doctoral studies in Madrid, Spain.

 

Source: Agencia Informativa CONACYT