The human fetus may be most vulnerable to Zika infection very early in pregnancy, a new study shows. Also, the lesser-known African strain of Zika might possibly cause nearly immediate death of the placenta.
The findings could lead to the development of stronger defenses in the global fight against Zika, researchers say.
Infection of pregnant women by the Asian strain of Zika virus has been linked to brain abnormalities such as microcephaly in their infants. It’s not clear, however, at what stage of pregnancy the human fetus is most susceptible to the disease.
R. Michael Roberts, professor of animal science and of biochemistry at the University of Missouri, says:
“Although the placenta is an effective barrier to the transmission of certain diseases and pathogens, the Asian strain, which has been linked to microcephaly in humans, is generally thought to cross through the placenta. Spread mostly by infected mosquitos, incidences of the virus can be found throughout US states and territories where more than 3,100 cases in pregnant women, mainly travelers from countries where the disease is widespread, have been reported to the Centers for Disease Control and Prevention.”
Infects In Early Pregnancy Stages
The researchers created placental cells from an approved line of pluripotent stem cells that were similar to early stage placentas. These placental cells were then infected with an Asian and African strain of Zika virus to determine how the placental cells were affected by the viruses.
Megan A. Sheridan, a graduate student in Roberts’ lab, says:
“Zika enters its target cells in a complex, multistep process. We found that the Asian strain of the virus infected and replicated in the cells; however, it didn’t kill the cells as readily.
Our research suggests that the Asian strain infects the placenta in the early stages of pregnancy and essentially ‘lies in wait’ where it is then transmitted to the fetus causing neurological disorders in infants such as microcephaly.”
The team noticed substantially different results when placental cells were introduced to the African strain of the Zika virus. When exposed, placental cells were killed within days, indicating that African strain of Zika could possibly cause miscarriages in infected mothers.
“The results from our testing of the African strain were unexpected,” Roberts says. “The cells were killed within 40-48 hours meaning that African Zika, while less prevalent, could be much more deadly during early pregnancy.
The findings suggest that the developing fetus could be most vulnerable to infection by Zika virus and other pathogens during a relatively narrow window within the first trimester of pregnancy.”
The research was supported by the National Institutes of Health and Fundação de Amparo a Pesquisa do Estado de São Paulo.
Megan A. Sheridan, Dinar Yunusov, Velmurugan Balaraman, Andrei P. Alexenko, Shinichiro Yabe, Sergio Verjovski-Almeida, Danny J. Schust, Alexander W. Franz, Yoel Sadovsky, Toshihiko Ezashi, and R. Michael Roberts Vulnerability of primitive human placental trophoblast to Zika virus PNAS 2017 114 (9) E1587-E1596; doi:10.1073/pnas.1616097114
Image: Maurizio De Angelis, Wellcome Images