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Zika Hijacks Pregnant Woman's Immune System

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MONDAY, Aug. 21, 2017 (HealthDay News) -- The Zika virus thrives in pregnant women by suppressing their already dampened immune systems and running roughshod over their body's natural defenses, which allows the virus to directly attack the fetus, a new study reports.

A woman's immune system naturally suppresses itself during pregnancy to keep the body from recognizing the fetus as a foreign body and attacking it, explained senior researcher Jae Jung, chair of the department of molecular microbiology and immunology at the University of Southern California's Keck School of Medicine.

Zika hijacks this process, turning off most of a pregnant woman's immune defense so the virus can spread unhindered, Jung said.

"The virus really tricks the host's immune system," Jung said. "It commandeers the pregnant woman's immune strategy to protect the fetus and utilizes that strategy for its own benefit."

This helps explain why Zika causes no symptoms at all in four out of five infected people, but can cause horrible neurological birth defects such as microcephaly when pregnant women become infected, Jung said.

Babies born with microcephaly have underdeveloped brains and skulls. Nearly 3,000 cases of microcephaly have been associated with Zika-infected mothers, researchers said in background information.

For their study, Jung and his colleagues tested both the African and Asian strains of Zika in the blood samples of healthy men and women, as well as samples taken from pregnant women.

Zika was first discovered in Africa in 1947, and that strain has not been associated with neurological birth defects, Jung said.

But the virus subsequently traveled to Asia, where it mutated and became more dangerous to pregnant women and their unborn babies, Jung said.

In the laboratory, the research team discovered that the Asian strain of Zika targets monocytes, which are white blood cells that mount the body's immune defense by destroying viruses and bacteria, Jung said.

Average people shrug off this attack, but pregnant women fall prey to it because Zika exploits the existing process by which the body protects a fetus from immune attack.

In pregnant women, a certain number of monocytes essentially flip roles and become immune-suppressing, encouraging the immune system to power down, Jung said.

Zika latches on to that natural process and amps it up.

"About 5 percent of a pregnant woman's monocytes have immune-suppressive activity," Jung said. "African Zika virus pushes the 5 percent up to around 10 percent. By comparison, Asian Zika virus turns 70 percent of her monocytes toward immune-suppressing."

This effect mainly occurs in the first and second trimester, researchers found. During the third trimester, the blood of infected pregnant women was about the same as that of non-pregnant women.

"The virus goes in, replicates, grows and then crosses the placenta to enter the fetus and cause disease," Jung said.

The blood of pregnant women infected with Zika also showed abnormally high expression of two genes that have been previously associated with pregnancy complications, researchers report.

One gene, ADAMTS9, has been associated with underweight newborns and difficult deliveries, while the gene FN1 has been associated with womb abnormalities that can lead to unusually small babies and preeclampsia, the study said.

Uncovering more about Zika's infection process will help researchers develop countermeasures against the virus, said Dr. Amesh Adalja, a senior associate for the Johns Hopkins Center for Health Security.

"This is a very important study that will likely lead to further research to develop potential methods to prevent this cascade from happening," Adalja said.

However, this study shows that future Zika vaccine trials need to take into account this increased risk to pregnant women, Jung said. None of the current clinical trials for a Zika vaccine include pregnant women, due to concern for fetal health.

"The Zika virus vaccines in development seem to be highly effective, but they're being tested among non-pregnant women with different body chemistry compared to pregnant women," Jung said in a news release.

"It's feasible the recommended vaccine dose -- though effective for non-pregnant women -- may not be potent enough for pregnant women because their bodies are more tolerant of viruses," Jung said.

The study was published Aug. 21 in the journal Nature Microbiology.

More information

For more on Zika and pregnancy, visit the U.S. Centers for Disease Control and Prevention.

SOURCES: Jae Jung, Ph.D., chair, department of molecular microbiology and immunology, University of Southern California's Keck School of Medicine; Amesh Adalja, M.D., senior associate, Johns Hopkins Center for Health Security, Baltimore; Aug. 21, 2017, Nature Microbiology
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