Mom-to-Be's Immune Response May Trigger Zika Birth Defects

From - January 5, 2018

Mom-to-Be's Immune Response May Trigger Zika Birth Defects

FRIDAY, Jan. 5, 2018 -- Zika might not directly cause the miscarriages and birth defects that have been associated with the notorious virus, a new study in mice suggests.

Instead, the ravaging effects of Zika infection on a developing fetus appear to stem from the immune response of the expecting mother, researchers said.

Lab mice bred without a key step in their immune response wound up birthing pups that survived Zika infection, while normal mice either lost their pregnancy or produced very underweight pups, the study found.

"The antiviral response generated in response to Zika infection is causing the miscarriage of the fetus, as opposed to the virus itself," according to senior researcher Akiko Iwasaki. She is a professor of immunobiology at the Yale University School of Medicine.

Iwasaki and her colleagues are now investigating whether a woman's immune response also causes some or all of the birth defects associated with Zika. One of the most serious of these birth defects is microcephaly, in which a newborn's brain and skull are severely underdeveloped.

The lab study revolved around a key signaling protein for the immune system, called type 1 interferon. The body produces type 1 interferon in response to a viral infection, and the protein in turn mounts a rapid and potent multipronged defense intended to keep the virus from spreading.

The researchers suspected that an interferon deficiency might explain why some pregnancies are more affected by Zika infection than others -- because, in those cases, the immune system would not respond as strongly to the infection.

To test this theory, they bred lab mice that lacked receptors for the immune protein.

"We thought the fetuses missing this interferon receptor would be more susceptible to death from Zika infection, and the fetuses that had the receptor signaling would be protected," Iwasaki said.

"What we found was quite the opposite," she said. "The fetuses unable to respond to interferon survived infection, and those that had the receptor, either they all died or were very small."

Mice and humans share many biological characteristics, which means that the response is likely to be the same in people, Iwasaki said.

However, research in animals frequently does not produce similar results in humans.

Exploring the matter further, the researchers cultured human placental tissue in the lab and then exposed the tissue to interferon, Iwasaki said. The cells wound up becoming deformed, featuring abnormal, knotty structures that previously have been linked to high-risk pregnancies.

Continue reading at »