Zika is a blood-borne pathogen primarily transmitted through mosquito bites and sexual activities. Pregnant women infected by Zika can pass the virus to their fetus, causing microcephaly, a condition in which the baby has an abnormally small head indicative of abnormal brain development. With the outbreak of the Zika virus and its consequences for pregnant women and their babies, much research has focused on how the infection leads to microcephaly in fetuses.

Current Zika research has been focused on uncovering methods for early detection of Zika in pregnant women and educating the public on safe sexual practices to contain the vector of transmission to just mosquitoes.1 However, to truly end the Zika epidemic, there are three critical steps that need to be taken. First, researchers must determine the point at which maternal infections harm the neurological development of fetuses in order to ensure treatment is administered to the mothers before the brain damage becomes irreversible. Subsequently, researchers must determine the mechanism through which Zika spreads from mother to fetus. After this step, researchers can begin developing therapies to protect the fetus from Zika once the mother is already infected and also start creating a preventative vaccine. Although Zika seems like a mysterious new illness, there are several other well-studied viral infections that affect pregnancies, such as cytomegalovirus (CMV). CMV infection during pregnancy also leads to severe fetal brain damage. Previous research techniques could provide clues for researchers trying to understand more about Zika, and learning more about Zika will better equip us for handling prenatal viral outbreaks in the future.

The current detection of microcephaly of infants with Zika-infected mothers involves fetal ultrasound as early as 18 weeks into the gestation period.2 However, this is a late diagnosis of fetal Zika infection and at this point the brain abnormalities caused by the virus are irreversible. Ultrasounds and MRI scans of infants with confirmed CMV infection can detect these neurological abnormalities as well.3 However, these brain lesions are also irreversible, making early detection a necessity for CMV infections as well. Fortunately, the presence of CMV or CMV DNA in amniotic fluid can be used for early diagnosis, and current treatment options include administration of valacyclovir or hyperimmunoglobulin in the window before the fetus develops brain lesions.4 Researchers must try to identify fetal Zika infection as early as possible as opposed to relying on fetal microcephaly as the sole diagnostic tool. Some potential early detection methods include testing for Zika in the urine of pregnant women as soon as Zika symptoms are present, as opposed to screening the fetus for infection.5

Discovering the mechanism through which Zika infects the fetus is necessary to develop therapies to protect the fetus from infection. Many viruses that are transferred to the fetus during pregnancy do so by compromising the immune function of the placental barrier, allowing the virus to cross the placenta and infect the fetus. The syncytiotrophoblast is the epithelial covering of placental embryonic villi, which are highly vascular finger-like projections that increase the surface area available for exchange of nutrients and wastes between the mother and fetus.6 In one study, experiments found that infection of extravillous trophoblast cells decreased the immune function of the placenta, which increased fetal susceptibility to infection.7 Determining which cells in the placenta are infected by Zika could aid research into preventative treatments for fetal infection.

Since viruses that cross the placental barrier are able to infect the fetus, understanding the interaction between immune cells and the placental barrier is important for developing therapies against Zika that increase fetal viral resistance. In one study, researchers found that primary human trophoblast cells use cell-derived vesicles called exosomes to transfer miRNA, conferring placental immune resistance to a multitude of viruses to other pregnancy-related cells.8 miRNAs are responsible for regulating gene expression, and different miRNAs exist in different cells so that those cells will have specific functions and defenses. Isolating these miRNA exosomes, using them to supplement placental cell strains, and subsequently testing whether those cells are more or less susceptible to Zika could support the development of drugs that bolster the placental immune defense mechanism already in place. Since viral diseases that cross the placenta lead to poor fetal outcome, developing protective measures for the placenta is imperative, not only for protection against Zika but also for protection against new viruses without vaccinations.9

Combating new and more elusive viral outbreaks is difficult, but understanding and preventing viral infection in fetuses is like taking a shot in the dark. Although the prospects for infants infected by Zika are currently poor, combining the research done on other congenital infections paints a more complete picture on viral transmission during pregnancy. Instead of starting from scratch, scientists can use this information to determine the tests that can detect Zika, the organs to examine for compromised immune system function, and the treatment types that have a higher probability of effectiveness. Zika will not be the last virus that causes birth defects, but by combining the efforts of many scientists, we can get closer to stopping fetal viral infection once and for all.

References

  1. Wong, K. V. J. Epidemiol. Public Health Rev. 2016, 1.
  2. Mlakar, J., et al. N. Engl. J. Med. 2016, 374, 951-958.
  3. Malinger, G., et al. Am. J. Neuroradiol. 2003, 24, 28-32.
  4. Leruez-Ville, M., et al. Am. J. Obstet. Gynecol. 2016, 215, 462.
  5. Gourinat, A. C., et al. Emerg. Infect. Dis. 2015, 21, 84-86.
  6. Delorme-Axford, E., et al. Proc. Natl. Acad. Sci. 2013, 110, 12048-12053.
  7. Zhang, J.; Parry, S. Ann. N. Y. Acad. Sci. 2001, 943, 148-156.
  8. Mouillet, J. F., et al. Int. J. Dev. Bio. 2014, 58, 281.
  9. Mor, G.; Cardenas I. Am. J. Reprod. Immunol. 2010, 63, 425-433.

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