Zika may hijack mother-fetus immunity route

November 14, 2018, Emory University
Zika virus particles (red) shown in African green monkey kidney cells. Credit: NIAID

To cross the placenta, Zika virus may hijack the route by which acquired immunity is transferred from mother to fetus, new research suggests.

The results are scheduled for publication in Cell Host & Microbe.

Antibodies against dengue make it easier for Zika to infect certain immune cells in the placenta, called Hofbauer cells. This effect was observed in both cell culture and in explanted human placental tissue, says lead author Mehul Suthar, Ph.D., assistant professor of pediatrics at Emory University School of Medicine and Emory Vaccine Center.

Zika during pregnancy can lead to overt microcephaly—a smaller head and brain—in the developing fetus, as well as more subtle neurological problems detectable later.

Researchers had previously observed that syncytiotrophoblasts, cells that make up outermost layer of the placenta, are resistant to Zika infection. Yet studies of Zika-infected pregnant women show that the virus is present in the placenta in the majority of cases.

"We needed to know how the virus gets across the placenta," Suthar says. "Previous studies have shown that Zika persists in the placenta for months. It's clearly getting in there."

However, Suthar says his team's research does not directly address the question of whether having anti-dengue antibodies—as a result of infection or vaccination—will worsen clinical outcomes in Zika infection.

Zika is similar genetically to dengue, they belong to the same flavivirus family and antibodies to one virus sometimes will bind the other. Both are transmitted by the same mosquito vector and their geographical infection patterns overlap in Central and South America, some parts of Africa and South Asia.

There are four strains of , and infection with one strain does not lead to long-lasting immunity against the other three. In fact, secondary infection with a different strain can increase the risk of developing a more severe illnesses like and/or .

This is thought to happen through "antibody-dependent enhancement": pre-existing antibodies to the first strain, unable to stop the secondary infection, instead bind to immune cells and help the new strain infect them.

On a cellular level, a similar phenomenon is occurring with Zika and dengue. When anti-dengue antibodies are present at the same time as Zika virus, they form complexes (clumps), which are taken up by the placenta.

This is a normal process; it's how the mother can transfer acquired immunity to the fetus. The placental cells grab onto antibodies by their Fc receptors, which are unvarying between antibodies. The Zika immune complexes increase viral binding and entry into Hofbauer cells, but also push them to mute antiviral responses.

"This is not the only mechanism," Suthar says. "There may be others."

"Once the virus crosses into the , it's down-hill from there," he adds, explaining that the fetal blood-brain barrier is not well-developed and viruses can then access brain tissue directly.

Suthar emphasized that using explanted human placental tissue, it could be possible to look for protective agents that could reduce the probability that Zika will cross the placental barrier. One possibility could be antibodies lacking Fc receptors, he says.

Suthar says his team is planning to investigate similar interactions with other viruses from the same family as dengue and Zika, such as West Nile virus.

Explore further: How Zika infects the placenta

More information: Cell Host & Microbe (2018). DOI: 10.1016/j.chom.2018.10.008

Related Stories

How Zika infects the placenta

May 27, 2016
Zika virus can infect and replicate in immune cells from the placenta, without killing them, scientists have discovered. The finding may explain how the virus can pass through the placenta of a pregnant woman, on its way ...

Antibodies to dengue may alter course of Zika virus infection

June 27, 2016
Scientists at Emory Vaccine Center, in collaboration with investigators from Thailand, have found that people infected with dengue virus develop antibodies that cross-react with Zika virus.

Study identifies how Zika virus infects the placenta

August 18, 2016
In a new study, Yale researchers demonstrate Zika virus infection of cells derived from human placentas. The research provides insight into how Zika virus may be transmitted from expectant mother to fetus, resulting in infection ...

Zika virus blindfolds immune alarm cells

February 2, 2017
Gatekeeper immune cells are fighting Zika virus with an arm tied behind their backs, scientists from Emory Vaccine Center report.

Prior dengue or yellow fever exposure does not worsen Zika infection in monkeys

August 4, 2017
Rhesus macaques previously infected with dengue or yellow fever viruses appear to be neither more nor less susceptible to severe infection with Zika virus, according to new research published in PLOS Pathogens.

Research provides clues to how Zika virus breaches the placental barrier

September 15, 2016
New research reveals that in pregnant women, Zika virus infection damages certain cells that affect placental formation and function. Furthermore, herpes simplex virus-2 (HSV-2) infection augments placental sensitivity to ...

Recommended for you

Study identifies a key cellular mechanism that triggers pneumonia in humans

December 11, 2018
The relationship between influenza and pneumonia has long been observed by health workers. Its genetic and cellular mechanisms have now been investigated in depth by scientists in a study involving volunteers and conducted ...

Effect of oral alfacalcidol on clinical outcomes in patients without secondary hyperparathyroidism

December 11, 2018
Treatment with active vitamin D did not decrease cardiovascular events in kidney patients undergoing hemodialysis, according to a research group in Japan. They have reported their research results in the December 11 issue ...

Human antibody discovery could save lives from fungal killer

December 11, 2018
A new way to diagnose, treat and protect against stealth fungal infections that claim more than 1.5 million lives per year worldwide has been moved a step closer, according to research published in Nature Communications.

Dialysis patients at risk of progressive brain injury

December 10, 2018
Kidney dialysis can cause short-term 'cerebral stunning' and may be associated with progressive brain injury in those who receive the treatment for many years. For many patients with kidney failure awaiting a kidney transplant ...

Silicosis is on the rise, but is there a therapeutic target?

December 6, 2018
Researchers from the CNRS, the University of Orléans, and the company Artimmune, in collaboration with Turkish clinicians from Atatürk University, have identified a key mechanism of lung inflammation induced by silica exposure, ...

PET scans to optimize tuberculosis meningitis treatments and personalize care, study finds

December 6, 2018
Although relatively rare in the United States, and accounting for fewer than 5 percent of tuberculosis cases worldwide, TB of the brain—or tuberculosis meningitis (TBM)—is often deadly, always hard to treat, and a particular ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.