Zika virus can be passed from a pregnant woman to her fetus. Infection during pregnancy can cause a birth defect called microcephaly and other severe fetal brain defects. By the end of 2015, a rise in the number of babies born with microcephaly, or unusually small heads, was found in Brazil. The epidemic was soon linked to the mosquito-borne Zika virus. However, there is no vaccine to prevent or treat Zika.
A new study by the researchers at the Washington University School of Medicine in St. Louis has found that the commonly used anti-malarial drug hydroxychloroquine may protect fetuses from the Zika virus. To learn more about how Zika breaches the placenta, the team infected human placental cells with Zika virus. The team noted that:
- The Zika virus infects the fetus by manipulating the body's normal barrier to infection.
- Exposure to the virus activated genes related to autophagy (the cellular waste-disposal pathway by which cells grind up debris, unwanted organelles and invading microbes)
- Drugs that ramped up autophagy increased the number of cells infected with Zika virus
- Drugs that suppressed autophagy resulted in fewer placental cells infected with Zika virus
To verify these findings, they conducted experiments on mice.
- 2 groups of pregnant mice were infected with Zika - one in which the autophagy process was disrupted, and the other group in which this process worked normally.
- 5 days after infection, the mice with a weak autophagy response had approximately the same amount of virus in their bloodstream as the mice with a normal response. However, in mice with a weak autophagy response, 10 times fewer viruses were found in the placenta and the heads of fetuses, and less damage to the placentas.
The researchers concluded that Zika virus took advantage of the autophagy process in the placenta to promote its survival and infection of placental cells.
Since hydroxychloroquine suppresses the autophagy response, the researchers considered whether it could also protect fetuses against Zika. They repeated the mouse experiment using only mice with a normal autophagy response. Female mice at day nine of pregnancy with a normal autophagy response were infected with Zika and then dosed with hydroxychloroquine or placebo every day for the next five days.
Following treatment, significantly less virus was found in the fetuses and placentas from the mice that had received hydroxychloroquine. Also, placentas showed less damage and the fetuses regained normal growth. The results indicate that the malaria drug hydroxychloroquine effectively blocks viral transmission to the fetus, even when the virus was circulating through the mother. This particular drug is already approved for use in pregnant women for other medical purposes.
According to the senior author Indira Mysorekar, PhD,"This drug already is used in pregnant women to treat malaria, and we suggest that it warrants evaluation in primates and women to diminish the risks of Zika infection and disease in developing fetuses. Our study suggests that an autophagy-based therapeutic intervention against Zika may be warranted in pregnant women infected with Zika virus."
Though this drug has been used safely in pregnant women for short periods of time, the researchers caution that further studies are needed before it can be used in pregnant women to avoid Zika. CDC recommends special precautions for pregnant women to prevent Zika, such as wearing long-sleeved shirts and long pants, using screens on windows and doors, and eliminating standing water to avoid mosquitoes.