Researchers investigate the effect of previous exposure to dengue virus on the likelihood of infection by the Zika virus.

 The Zika virus has been recognized for over 70 years and observed to cause small, local outbreaks until the rapid spread of the virus and resulting epidemic in 2013–2014. During this outbreak, the link between Zika infection in pregnant women and the development of congenital neurodevelopmental disease in babies was first identified.

Like yellow fever virus and dengue virus, the Zika virus is a flavivirus that triggers the production of antibodies, or immunoglobulins, that fight the virus. Some are specific to a given flavivirus, while others can affect multiple flavivirus species, a behavior known as cross-reactivity.

Although these antibodies generally protect people from infection by flaviviruses, there are rare examples when they can lead to more severe cases of a disease. One such example involves the antibodies produced during the first infection by the dengue virus. People infected a second time by a different serotype of the dengue virus can have more serious responses.

Because the dengue virus is present in many of the same parts of the world as the Zika virus, researchers considered that the appearance of congenital disease in pregnant women infected by the Zika virus might be attributed to cross-reactive antibodies produced during prior exposure to the dengue virus.

The scientists examined the Zika outbreak in Salvador, Brazil, focusing on people already participating in a long-term study of dengue virus infection. They used serological assays to measure Zika antibody levels before, during and after the 2015 Zika epidemic to determine the prevalence of infection among the study population. The assay used by the researchers was designed to detect ZIKV NS1-reactive IgG3 antibodies, which are transiently present in serum and believed to indicate recent ZIKV infection.

Before the Zika virus was introduced in the population, very few serum samples contained ZIKV NS1-reactive IgG3 antibodies. Within five months of the first report of a Zika infection in Salvador, however, most of the samples contained the antibodies. The level of immunity was estimated to be 73%.

Next, the scientists calculated the incidence of dengue virus infection using serum samples collected before the introduction of the Zika virus. A logistic regression statistical approach was applied to determine the probability of Zika virus infection as a function of the quantity of IgG antibodies that react against the NS1 protein of the dengue virus.

The researchers found that the concentration of dengue virus NS1-reactive IgG antibodies for all subclasses together was inversely correlated with the probability of ZIKV infection, suggesting that dengue virus immunity has a protective effect against subsequent ZIKV infection.  On the other hand, when they looked at the dengue virus NS1-reactive molecules of the IgG3 subclass, they found a positive correlation between the concentration of these antibodies and the frequency of ZIKV infection, suggesting that recent exposure to the dengue virus transiently increases the susceptibility of an individual to ZIKV infection.