Zika infection: Does the immune response contribute to fetal demise?

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Antiviral proteins termed interferons, which mount a potent immune response to Zika infection, may be responsible for detrimental effects on placental and fetal development, according to new research led by Yale University (CT, USA).

It has previously been established that type I interferons are required to fight Zika infection in mothers – past studies have demonstrated that adult mice lacking interferon receptors are highly susceptible to Zika. However, the role of interferons in the immune defense of fetuses remained unclear. [/userpro_private]

This study, published recently in Science Immunology, assessed two different mouse models; one lacking type I interferon receptor, the other with only one copy of the type I interferon receptor gene. On infection with Zika virus, the team observed that fetuses without the receptor had higher virus levels than those with the receptor.

However, the researchers also noticed that in the mice with one copy of the receptor there were signs of abnormal placental development, restricted fetal growth and fetal death. The team observed a variety of structural and molecular changes including underdeveloped blood vessels in the placenta, an abnormal barrier between maternal and fetal cells and evidence of cellular stress. These findings suggest that interferons may act as a checkpoint during pregnancy and that, although critical in blocking viral replication, too much of this protein could have adverse effects during pregnancy.

In addition, the study proposed that it might be the host’s response to Zika, and not Zika itself, which contributes to fetal complications. The team investigated the theory further in a human model, testing the impact of interferons on human placenta. They discovered that when exposed to interferon-β the placenta developed abnormal knot structures, results that may have implications in Zika and also other pregnancy complications, for example, in women with autoimmune diseases.

Looking forwards, the team hope to look into interferon levels at different time points during pregnancy, with the view to assessing if this pathway is involved in other infections such as rubella and herpes.

Author, Akiko Iwasaki, from Yale University, concluded: “Pregnancy is a huge investment for a mother. Our work shows how this signaling pathway works to terminate pregnancies that are not going to be viable early on,

“If we could prevent or treat the interferon response in women with these diseases pregnancy may go better for them.”

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Source: https://www.eurekalert.org/emb_releases/2018-01/hhmi-hzi010118.php

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