Prior dengue infection may ‘defuse’ Zika virus

The Zika virus outbreak in Latin America has so far affected more than 60 million people. The infection can have devastating consequences for pregnant women and their children, many of whom are born with a type of brain malformation known as microcephaly. Prior infection with the genetically related dengue virus had been assumed to enhance the effects of subsequent Zika virus infection. Researchers from Charité – Universitätsmedizin Berlin and the German Centre for Infection Research (DZIF) have now shown that prior dengue infection protects against damage associated with Zika. Results from this research have been published in Emerging Infectious Diseases*.

“We already know that Zika virus infection during pregnancy can damage the fetus, leading to microcephaly and other potentially serious symptoms,” explains the study’s lead investigator, Prof. Dr. Felix Drexler of Charité’s Institute of Virology. Prof. Drexler has been working with the DZIF for many years, developing diagnostic tests for Zika and other viruses. “Until now, however, we failed to understand why there is an increased incidence of Zika-associated microcephaly in certain areas such as the Northeast of Brazil,” says Prof. Drexler. The international team of researchers set out to look for cofactors which might be responsible for determining whether a Zika virus infection during pregnancy will have devastating consequences.

The dengue virus, which is responsible for dengue fever and is widely spread across Latin America, was suspected to be one such cofactor. Initially, the researchers assumed that it was the human antibodies produced in response to prior dengue virus infection which might contribute to the fetal damage caused during subsequent infection with the Zika virus. It had been known for some time that, under certain conditions, these antibodies are capable of enhancing the effects of subsequent dengue infections with a different dengue virus serotype. In the case of Zika, however, the opposite appears to be true. “Surprisingly, our study shows that previous dengue infection protects against Zika-associated damage,” emphasizes Prof. Drexler.

In order to study interactions between dengue and Zika viruses, the researchers first compared the genomes of all known dengue viruses currently found in Brazil. They did so to establish whether, over the past few decades, the Northeast of Brazil had been exposed to different dengue viruses than those found in other regions, and whether people in the Northeast had developed different immunity as a result. They also conducted tests on 29 mothers who had developed Zika virus infection during pregnancy and whose babies were later born with microcephaly. These tests were conducted to determine whether these women had antibodies against the four types of dengue virus found in the area. 108 mothers who were seropositive for Zika virus infection but whose children were born healthy served as controls.   

Summarizing the findings of the study, Prof. Drexler says: “The results show that preexisting immunity against dengue virus significantly reduces the risk of Zika virus infection resulting in serious consequences for the unborn child. People with prior dengue infection therefore need not worry about subsequently developing more severe forms of Zika infection.” This is both an important and reassuring message for pregnant women. It means that the researchers’ initial suspicion – that the dengue virus might act as a cofactor for severe Zika virus infection in the unborn child – could not be confirmed. By continuing to look for other cofactors, the researchers are hoping to explain the increased incidence of microcephaly in the northeastern region of Brazil and to find ways to identify the development of microcephaly early on.

* Pedroso C et al. Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil. Emerg Infect Dis. 2019 Aug 17;25(8). doi: 10.3201/eid2508.190113.

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