Science: Explaining previous Zika virus infections can increase the risk of severe dengue virus infection.

!--webeditor: page title" -- In a new study, --- researchers from the United States and Nicaragua have found that the mosquito-borne Zika virus makes people more susceptible to dengue later in life, and that when they do develop dengue, they suffer from more severe symptoms.
study was published in the August 28, 2020 issue of the Journal of Science under the title "Zika virus virus enhances future risk of severe dengue disease."
images from Science, 2020, doi:10.1126/science.abb6143.
study used data from two groups of Nicaraguan children who had experienced Zika outbreaks in 2016 and dengue outbreaks in 2019.
the first time it has investigated the effects of Zika immunization on dengue fever in humans.
these findings confirm earlier speculation that antibodies to the Zika virus, usually designed to protect the body from infection, may actually interact with the dengue virus, making dengue infection worse.
this interaction, known as antibody-dependent enhancement, may make it harder to design a vaccine that is safe and effective while protecting the Zika virus from increasing the risk of dengue infection. Leah Katzelnick, lead author of the
paper and a postdoctoral scholar at the University of California, Berkeley School of Public Health, said, "The key issue that our study identifies is that previous infections with the Zika virus do significantly increase your risk of developing symptomatic and more severe dengue fever."
the findings raise the question: Will vaccines targeting the Zika virus increase people's risk of more severe dengue fever? How do you design a Zika vaccine that induces only good antibodies that protect you from the Zika virus, but not other antibodies that can worsen the disease? "A related viral family of dengue fever is caused by four closely related dengue virus serotypes, each with slightly different symptoms and severity.
one type of dengue virus increases a person's likelihood of developing a more serious disease when infected with another type of dengue virus.
, when a person is infected with two types of dengue virus, they usually receive a degree of immune protection against the severity of future dengue disease.
late 2015, when the Zika virus first appeared in Latin America, many speculated whether the virus, as a close relative of the dengue virus, would interact with the virus in a similar way.
first question is, 'How did previous dengue virus infections affect the Zika virus?'" said Eva Harris, a professor of infectious diseases and vaccines at the University of California, Berkeley and author of the paper. 'This is because everyone in Latin America is, to some extent, eventually immune to the dengue virus and carries antibodies to the dengue virus.
" Since 2004, Harris and her colleagues have monitored some 3,800 children living in Managua, the country's capital, in Nicaragua to track any signs of dengue fever and collect annual blood samples to test the virus and its antibodies.
when another mosquito-borne chikungi and Zika virus appeared in Nicaragua in 2014 and 2016, respectively, this group of children was expanded to obtain cases of these emerging pathogens.
Harris used data from this group of children to publish a study in 2019 that suggested that previous dengue virus infections could provide little protection against the Zika virus, and other studies now support that conclusion.
but a reverse question, whether Zika virus antibodies are protecting the future of dengue disease or whether it has the potential to enhance dengue disease, remains a mystery.
arrived in Managua during the outbreak in July 2019, Harris arrived in Managua with Katzelnick, who will spend the rest of the year in the Nicaraguan capital as a Fogerty Global Health Researcher.
arrival comes at a time of a massive outbreak of dengue 2, the first large-scale outbreak of the virus since the 2016 Zika outbreak.
type 2 dengue virus is one of the more serious of the four serotypes of dengue virus.
the dengue outbreak spreading in real time, and we started thinking about a lot of cases," Harris said.
I want to know if previous zika infections have caused people to develop symptomatic dengue fever? The researchers collected data from this group of children and another study of children treated at a nearby pediatric hospital.
mid-autumn, they had enough evidence to prove that people with previous Zika infections were more likely to be infected with the symptomatic dengue virus.
as the number of cases increases, they find that previous infections with the Zika virus can also increase the severity of dengue fever.
the researchers used a pool of blood samples from the children's group and traced it back to 2004 to investigate other disease patterns.
they found that people who had been infected with the dengue virus once and then with the Zika virus still had a high risk of a second, more severe dengue infection.
addition, when a person is infected with two consecutive dengue virus infections, the type of dengue virus that causes a second infection affects whether the person is protected or experiences enhanced dengue disease.
think it can really help us understand the coming epidemic," Harris said.
, for example, if you experienced a type 2 dengue outbreak after the Zika outbreak, you know to prepare your hospital for people who are more likely to develop more serious illnesses.
when we get sick, our bodies produce a large molecular protein called antibodies to help our immune system fight infection," he said.
these antibodies have specific chemical shapes that allow them to adhere to the pathogens of concern, marking the intruder's immune cell breakdown.
for viruses such as Zika and dengue, they can also be wrapped in these viruses, preventing the virus from entering human cells, effectively snring the virus.
!--/ewebeditor:page--!--ewebeditor:page"--when antibodies designed to attach to a virus, such as Zika, try to bind to a slightly different virus, such as dengue virus, antibody dependence increases.
antibodies to the Zika virus can be attached to the dengue virus, but not enough to contain them.
, when passing immune cells detect these antibodies and try to break down the dengue virus, they may actually end up infected with the virus.
, "This mechanism not only allows the virus to enter more cells for infection, but also inhibits the immune response of those cells, causing the virus to produce more viruses," Katzelnick said.
given that they are immune cells, they move around the body.
, they can cause larger infections.
" in a 2017 study, Katzelnick, Harris and their team showed that infection with a dengue virus can be enhanced by antibody dependence, leading to a more severe infection of the second dengue virus.
While this mechanism complicates the search for effective vaccines against The Zika and Dengue viruses, Katzelnick and Harris say it is still possible to design vaccines that stimulate the body to produce antibodies that bind only to the target virus rather than other viruses.
, "The Zika virus remains a terrible problem, with many complex ethical considerations, in part because it affects pregnant women and may also affect their children," Katzelnick said.
I really hope that people will continue to work very hard to find ways to develop a safe vaccine, even if it is more challenging than we first thought.
" (bioon.com) Reference: 1. Leah C. Katzelnick et al. Zika virus infected enhances future risk of severe dengue disease. Science, 2020, doi:10.1126/science.abb6143.2. Hannah Clapham. Zika virus increases risk of dengue disease. Science, 2020, doi:10.1126/science.abd5922.Prior Zika virus infected increases risk of severe dengue disease.