Authors: Martha Powell, Future Science Group
Researchers have demonstrated the potential of a licensed antimalarial, hydroxychloroquine, to protect fetuses from Zika infection in mouse models. Although further studies are needed, this could present an avenue for an interventional drug in pregnant women.
Developing fetuses are particularly vulnerable to infection, and previous studies on Zika viruses have demonstrated its ability to cross and thrive in the placenta, causing devastating consequences such as microcephaly.
In this study, published in The Journal of Experimental Medicine, the team from Washington University School of Medicine (MO, USA) built on previous findings regarding Zika virus and its propensity for transmission cross the placenta.
The researchers first examined Zika infection in human placental cells, discovering that viral exposure activated genes related to the autophagy pathway. However, when they tested drugs that increase the autophagy pathway, the team observed an increase in the number of Zika-infected cells, whereas drugs that inhibited this pathway were linked with a decrease in infected cells. Author, Bin Cao (Washington University), explained: “It appears that Zika virus takes advantage of the autophagy process in the placenta to promote its survival and infection of placental cells.”
The team then examined the role of the autophagy response in mice models of Zika in pregnancy. After 5 days of Zika infection, they observed that, when compared to controls, mice with an inhibited autophagy pathway had very similar levels of Zika virus in the blood. However, the group discovered that in the mice with decreased autophagy ability, there were 10-times fewer viruses in both the placenta and heads of fetuses, in addition to reduced placental damage.
The team then investigated malaria drug hydroxychloroquine, which is known to suppress the autophagy response. The team randomized pregnant mice to receive either the antimalarial or a placebo for 5 days, discovering significantly fewer viruses in the fetuses and placentas of mice taking hydroxychloroquine. Despite similar levels of Zika in the mother’s blood, mice receiving hydroxychloroquine appeared to have less placental damage, moreover, fetuses regained normal growth after infection.
Senior author Indira Mysorekar, from Washington University, commented: “We found that the malaria drug hydroxychloroquine effectively blocks viral transmission to the fetus, 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.”
This study is the first to demonstrate that hydroxychloroquine could provide protection for fetuses in a Zika infection; however, the team have stated that caution is required. Although hydroxychloroquine has been safely used in pregnant women, this has only been for short periods and further studies would be needed to assess the safety of hydroxychloroquine for long-term use, such as throughout the duration of pregnancy.
Mysorekar concluded: “We would urge caution but nevertheless feel our study provides new avenues for feasible therapeutic interventions. Our study suggests that an autophagy-based therapeutic intervention against Zika may be warranted in pregnant women infected with Zika virus.”