Mom-to-Be's Immune Response May Trigger Zika Birth Defects
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. She is also an investigator for the Howard Hughes Medical Institute, in Chevy Chase, Md.
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 doesn't 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.
According to Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, these findings open up a potential avenue for protecting the fetus of a woman infected with Zika.
"The consequences of any infectious disease are the result of an elaborate interaction between the immune system and the microbe, and it appears that Zika's impact on the fetus is another example of this phenomenon," he said. Adalja was not involved with the study but was familiar with the findings.
"Such a finding provides some basis for understanding if a therapeutic approach in which the effects of interferon are blocked might be beneficial," Adalja said.
Iwasaki, though, thinks this emphasizes the need for a Zika vaccine because "it's very tricky to treat women if they're already infected with the Zika virus," she said.
Instead, she thinks the real value in the study is a new understanding of how any viral infection might influence the health of a pregnancy.
"This has implications for other viral infections as well, because the same response would be generated for virtually every viral infection," Iwasaki said.
In particular, women with autoimmune disorders trying to have a baby could benefit from this research, Iwasaki said. These women aren't actually fighting off a virus, she explained, so interrupting their interferon immune response would not expose them to any harm and could preserve the health of their baby.
"If elevated interferon is a more general underlying mechanism for pregnancy complications, we might be able to interfere with the interferon signaling," Iwasaki said. "Because there's no viral infection to worry about, we might be able to help pregnancy carry through to term in those women who are suffering from autoimmune diseases."
The study was published in the Jan. 5 issue of the journal Science Immunology.
The U.S. Centers for Disease Control and Prevention has more on Zika virus.
SOURCES: Akiko Iwasaki, Ph.D., professor, immunobiology, Yale University School of Medicine, New Haven, Conn.; Amesh Adalja, M.D., senior scholar, Johns Hopkins Center for Health Security, Baltimore; Jan. 5, 2018, Science Immunology
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