Host and viral mechanisms of congenital Zika syndrome

ABSTRACT

In 2015–2016, in the Americas, and especially in northeast Brazil, a significant number of cases of microcephaly and other congenital brain abnormalities were linked with an outbreak of Zika virus (ZIKV) infection in pregnant women. While maternal symptoms of ZIKV are generally mild and self-limiting, clinical presentation in fetuses and newborns infected is extensive and includes microcephaly, decreased cortical development, atrophy and hypoplasia of the cerebellum and cerebellar vermis, arthrogryposis, and polyhydramnios. The term congenital ZIKV syndrome (CZS) was introduced to describe the range of findings associated with maternal-fetal ZIKV transmission. ZIKV is primarily transmitted by Aedes aegypti mosquitoes, however non-vector-dependent routes are also possible. Mechanisms of maternal-fetal transmission remain unknown, and the trans-placental route has been extensively studied in animal models and in human samples. The aim of this review was to summarize recent studies that helped to elucidate the mechanism of CZS in animal models and observational studies. There are still challenges in the diagnosis and prevention of CZS in humans, due to the large gap that remains in translating ZIKV research to clinical practice. Translational research linking governments, local health workers, scientists and industry is fundamental to improve care for mothers and children.

KEYWORDS:

• Placenta
• trophoblast
• hydroxychloroquine
• autophagy
• type I interferon
• interferon lambda

Acknowledgments

This work was supported by National Institutes of Health/National Institute of Child Health and Human Development grant R01HD091218 (to IUM) and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq) grant # 409605/2016-6 to MLC. Brooke Liang was supported by a Medical Research Fellowship Program from the Howard Hughes Medical Institute

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico [409605/2016-6]; Howard Hughes Medical Institute [Medical Research Fellowship Program]; National Institutes of Health (US) [R01HD091218]