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Biological Chemistry

Malaria drug prevents Zika-related birth defects in mice

Hydroxychloroquine stops pregnant mice from spreading virus to offspring

by Bethany Halford
July 17, 2017 | APPEARED IN VOLUME 95, ISSUE 29

Zika infection during pregnancy can cause devastating birth defects. Children born to mothers with Zika can have abnormally small heads and brains (a condition known as microcephaly), abnormal reflexes, epilepsy, as well as problems with vision, hearing, and digestion. Indira U. Mysorekar and coworkers at Washington University School of Medicine in St. Louis have discovered that in the placenta, Zika may be hijacking autophagy—cells’ process for removing toxins and recycling damaged components to generate energy—thereby infecting developing fetuses (J. Exp. Med. 2017, DOI: 10.1084/jem.20170957). The researchers infected pregnant mice that were missing an essential autophagy gene and found they had significantly lower levels of detectable virus and less placental and fetal damage compared with pregnant mice with the gene. They then looked to see how hydroxychloroquine, a malaria drug that inhibits autophagy, affects Zika-infected pregnant mice and their offspring. Nonmodifed mice given hydroxychloroquine also had less placental and fetal damage than untreated pregnant mice. This finding suggests that the drug, which is approved by the U.S. Food & Drug Administration for use in pregnant women to treat malaria and certain autoimmune disorders, prevents Zika from crossing the placenta barrier. Mysorekar hopes the work will lead to similar studies in nonhuman primates and, after that, people.

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