Scientists discover how Zika virus harms fetuses

Researchers have identified proteins potentially responsible for causing microcephaly.

By Carmen Heredia Rodriguez

Kaiser Health News

Scientists at the University of Southern California have discovered a key weapon used by the Zika virus to ravage the brains of infected fetuses: proteins.

In an article published last Thursday in the journal Cell Stem Cell, researchers identified two proteins in Zika potentially responsible for causing microcephaly.

Microcephaly is a birth defect in which a child’s head is smaller than the average size. A variety of factors can trigger the condition, according to the Centers for Disease Control and Prevention, including malnutrition, environmental agents and other viruses.

Although it is associated with brain damage, some children born with the disease never develop cognitive issues.

The proteins — called NS4A and NS4B — affect the brain by targeting a critical signaling pathway that controls cell growth and breaks down damaged cells and their elements.

Initially, Zika slows cell development and reduces the variety of cells in the brain.

Over time, this “rigged” system enables the virus to thrive and spread while healthy cells die.

The finding is the first step toward developing future drugs that could prevent Zika’s damaging effects, said Jae Jung, the study’s co-author and director of the USC Institute of Emerging Pathogens and Immune Diseases.

“Those two viral proteins are ultimately the target for therapy development,” he said.

Working with discarded tissue, the researchers infected fetal neural stem cells — a building block of the nervous system — with three different strains of the Zika virus.

Stem cells infected with the ZIKV strain, which is responsible for causing the current outbreak, died at rates more than four times higher than an uninfected brain.

The specific proteins in question kill neural cells by hijacking a signaling mechanism called AKT-Mtor pathway.

The pathway handles the process of breaking down damaged cells, also known as autophagy.

As Zika spreads in the developing fetus, the virus actually uses the disposal process to continue proliferating. Cells began dying as early as two weeks after infection occurred.

The Zika virus rose to prominence in 2015 after cases of an unknown disease were reported in Brazil.

Since then, the outbreak has affected more than 40 countries, including the United States.

The virus is spread by certain mosquitoes and can cause flu-like symptoms such as fever, muscle aches and joint pain in adults. Pregnant women are considered especially vulnerable because of the risk of microcephaly.

Dr. Kjersti Aagaard, a maternal-fetal medicine specialist at Texas Children’s Hospital Pavilion for Women and the Baylor College of Medicine, said microcephaly triggered by Zika is an urgent concern because of its association with brain malformation.

With the virus, Aagaard said, a smaller head likely encases a smaller brain affected by disease.

“Microcephaly is the endpoint of the damage,” she said.

Aagaard also noted that the virus can affect pregnant women in other serious ways, too.

The illness can lead to miscarriage, stillbirths and low amniotic fluid. In addition, some cases of ulcerative eye lesions associated with the illness have been reported.

But, some pregnant women who become infected never pass the virus to the fetus at all, Aagaard stressed.

Early screening is key in identifying if and when a fetus is affected by the infected mother.

“An infected mom does not equal an infected fetus,” she said. “And an infected fetus does not equal an affected fetus.”

Findings from the latest study have already prompted further research to develop various Zika drugs and vaccines.

Scientists are already working on a live, attenuated vaccine that will use a strain of the virus without the microcephaly-causing proteins, Jung said.

But questions remain, such as how these proteins interrupt the cell’s ability to regulate brain development. And while the scientists made this discovery in six months, Jung anticipates the next phase might take several years.

“We know where we are going but we need to find the detailed map,” he said.

Funding is also an issue. Congress left for recess in July without allocating monies for the Zika effort, which means labs that depend on government grants will be strapped for cash in the coming months.

But Dr. Gary Clark, chief of pediatric neurology and developmental neuroscience at Texas Children’s Hospital, said research should not be the medical community’s main priority.

Instead, authorities should refocus on educating pregnant women and travelers entering the country from affected areas to prevent the virus’ spread and protect future children from a lifetime of disability.

“I think that bottom line is that this virus causes brain damage,” he said. “And this is permanent.”

________

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation.

More in News

U.S. Sen. Patty Murray, D-Seattle, center, walks on a trail in Neah Bay with Tribal Chairman Timothy J. Greene Sr., left, and others. (Sen. Murray's office)
Murray tours West End facilities

Senator secured funding for road, medical center

Olympic Medical Heart Center director Leonard Anderson examines a new echocardiograph at the Port Angeles hospital facility. (Keith Thorpe/Peninsula Daily News)
Foundation donation aids OMC’s heart center

Echocardiogram machine to help more patients receive care locally

OMC providing facts about Proposition 1

Hospital sees $2.2M in savings following consultant tips

From left, Leland Gibson, Tucker Piontek and Jeff Matthews are lowered into the water aboard Fern, a Nordic folk boat commissioned by Michigan resident Charles Jahn, who was present to see his boat in the water for the first time on Friday at Port Townsend’s Boat Haven Marina. Fern was built over three years by three separate classes of students at The Northwest School of Wooden Boatbuilding. (Elijah Sussman/Peninsula Daily News)
Boat launched in Port Townsend

From left, Leland Gibson, Tucker Piontek and Jeff Matthews are lowered into… Continue reading

Maya DeLano, executive assistant at Composite Recycling Technology Center, demonstrates the durability of recycled carbon fiber during a job fair on Friday organized by the Port Angeles Chamber of Commerce at the Vern Burton Community Center. (Christopher Urquia/Peninsula Daily News)
Job fair in Port Angeles

Maya DeLano, executive assistant at Composite Recycling Technology Center, demonstrates the durability… Continue reading

Three generations of Bike the US for MS riders — from left, Michael Davies, Jordyn Davies and Richard Davies — visit the Sequim MS Support Group. (Sequim MS Support Group)
Bike the US for MS makes stop in Sequim

The Sequim Multiple Sclerosis Support Group continued its tradition of… Continue reading

Road work set next week on state Highway 20

Maintenance crews from the state Department of Transportation will… Continue reading

Recall petitions dismissed

Judge cites petitioner’s lack of standing

Clallam Transit awarded $3.6M grant

Agency plans to replace several buses in its fleet

Western hemlock could provide housing option

Mill processing trees, removing moisture content

Abbot Construction’s crew responsible for crane lifting the two-story concrete walls pack up as new crew members move in for steel reinforcement on Monday. (Elijah Sussman/Peninsula Daily News)
Jefferson Healthcare adding capacity, programs

Expanded services to be offered upon 2025 opening