Zika Virus Mapped from Mother to Fetus

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Researchers from the University of California-San Francisco (UCSF) have provided a roadmap for how the Zika virus travels from the blood of an infected pregnant woman to her fetus, providing new clues to the process by which the disease leads to birth defects.

Researchers from the University of California-San Francisco (UCSF) have provided a roadmap for how the Zika virus travels from the blood of an infected pregnant woman to her fetus, providing new clues to the process by which the disease leads to birth defects.

Their study, published July 18 in the journal Cell Host & Microbe and funded by a grant from the National Institute of Allergy and Infectious Diseases, revealed that the virus has two potential routes to the developing fetus in an infected pregnant woman: a placental route and a route across the amniotic sac. The former is established in the first trimester, according to the authors, and the latter develops in the second trimester.

“Very few viruses reach the fetus during pregnancy and cause birth defects,” study co-author Lenore Pereira, PhD, a virologist and professor of cell and tissue biology in the UCSF School of Dentistry, said in a statement released by the school in conjunction with the study’s publication. She added that this finding should provide fodder for “thinking about ways to protect the fetus when the mother gets infected.”

According to the UCSF team, Zika actually infects several different placental cell types—both within the placenta and outside the fetal membranes—when examined in isolated cells and as intact tissue explants. Interestingly, they found that the epithelial cells of the amniotic membrane surrounding the fetus were particularly susceptible to the virus.

“This suggests that these cells play a significant role in mediating transmission to the fetus and supports the hypothesis that transmission could occur across these membranes independently of the placenta, especially in mid and late gestation,” Dr. Pereira said in the statement.

The work is significant, of course, because of the fetal health complications that have been associated with Zika. Although the symptoms of the virus itself are relatively minor, pregnant women who fall ill are at high risk for delivering newborns with birth defects such as microcephaly. Dr. Pereira noted that these birth defects appear to occur when a woman is infected in the first or second trimester; however, other birth defects may occur as a result of infection in the third trimester.

Of particular note given the severe complications associated with the virus, the work of the UCSF team may have also identified a potential therapeutic target. Indeed, their work reveals that the Zika receptor TIM1 is strongly and consistently expressed throughout gestation; TIM1 binds to phosphatidylethanolamine, a membrane lipid present in Zika. Through experiments on human tissue in the lab, the UCSF authors found that the old-line antibiotic duramycin binds to phosphatidylethanolamine, which may mean that (even in low concentrations) it can block Zika from linking with TIM1 receptors and infecting cells. Duramycin has recently proved effective in clinical trials against dengue and West Nile, which are similar to Zika.

“Our paper shows that duramycin efficiently blocks infection of numerous placental cell types and intact first-trimester human placental tissue by contemporary strains of Zika virus recently isolated from the current outbreak in Latin America, where Zika virus infection during pregnancy has been associated with microcephaly and other congenital birth defects,” study co-author Eva Harris, PhD, professor of infectious diseases and vaccinology at the UC Berkeley School of Public Health said in the UCSF statement. “This indicates that duramycin or similar drugs could effectively reduce or prevent transmission of Zika virus from mother to fetus across both potential routes and prevent associated birth defects.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.

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