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U.S. Researchers Identify Key Weapon of Zika Virus

Proteins hijack autophagy pathway, kill neural cells

Scientists at the University of Southern California (USC) have discovered a key weapon used by the Zika virus to damage the brains of infected fetuses, according to an article published in Cell Stem Cell. The researchers identified two proteins in Zika potentially responsible for causing microcephaly.

The new findings were summarized in a recent report from Kaiser Health News.

The discovery is the first step toward developing future drugs that could prevent the damaging effects of Zika, said co-author Dr. Jae Jung, director of the USC Institute of Emerging Pathogens and Immune Diseases. “Those two viral proteins are ultimately the target for therapy development,” he said.

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

Working with discarded tissue, the researchers at USC infected fetal neural stem cells—building blocks of the nervous system—with three different strains of the Zika virus. Stem cells infected with a Zika strain that is responsible for the current outbreak died at rates more than four times higher than those in an uninfected brain. Cells began dying as early as two weeks after infection.

The specific proteins in question—NS4A and NS4B—kill neural cells by hijacking a signaling mechanism called the AKT-Mtor pathway. This pathway handles the process of breaking down damaged cells (autophagy). As Zika spreads in a developing fetus, the virus uses this disposal process to continue proliferating.

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 may take several years.

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

The Zika virus came 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.

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 viral infection, a smaller head likely encases a smaller brain ravaged by disease, Dr. Aagaard said.

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

The virus can affect pregnant women in other serious ways, according to Dr. Aagaard. Infection can lead to miscarriage, stillbirths, and low amniotic fluid. In some cases, the virus causes both mother and child to develop ulcers in the eye.

She stressed, however, that some pregnant women who become infected with Zika never pass it to the fetus. Early screening is key in identifying whether and when a fetus has been affected by its infected mother.

Sources: Kaiser Health News; August 11, 2016; and Cell Stem Cell; August 11, 2016.

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