Zika virus congenital syndrome: experimental models and clinical aspects

Abstract

Viral infections have long been the cause of severe diseases to humans, increasing morbidity and mortality rates worldwide, either in rich or poor countries. Yellow fever virus, H1N1 virus, HIV, dengue virus, hepatitis B and C are well known threats to human health, being responsible for many million deaths annually, associated to a huge economic and social cost. In this context, a recently introduced flavivirus in South America, called Zika virus (ZIKV), led the WHO to declare in February 1st 2016 a warning on Public Health Emergency of International Concern (PHEIC). ZIKV is an arbovirus of the Flaviviridae family firstly isolated from sentinels Rhesus sp. monkeys at the Ziika forest in Uganda, Africa, in 1947. Lately, the virus has well adapted to the worldwide spread Aedes aegypti mosquito, the vector for DENV, CHIKV, YFV and many others. At first, it was not considered a threat to human health, but everything changed when a skyrocketing number of babies born with microcephaly and adults with Guillain-Barré syndrome were reported, mainly in northeastern Brazil. It is now well established that the virus is responsible for the so called congenital Zika syndrome (CZS), whose most dramatic features are microcephaly, arthrogryposis and ocular damage. Thus, in this review, we provide a brief discussion of these main clinical aspects of the CZS, correlating them with the experimental animal models described so far.

Viral receptors for flaviviruses: Not only gatekeepers

“…Dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), Japanese encephalitis virus (JEV), tick‐borne encephalitis (TBE), and Zika virus (ZIKV) are the most important and the most studied members. Interestingly, flavivirus infection may cause conditions ranging from mild headache, fever, and cutaneous rash, to more severe outcomes, such as hemorrhagic fever, encephalitis, liver failure, Guillain‐Barré syndrome, and microcephaly . This is clear evidence not only of the epidemiologic and clinical relevance of such pathogens but also of the complexity of their biology in the host organism.…”

São Paulo School of Advanced Sciences on Vaccines: an overview

“…Due to the neurological damage and the eventual induction of microcephaly in infected babies, this virus recently occupied the spotlight worldwide. Beyond the onset of microcephaly, ZIKV brain infection can also result in growth impairment, placenta damage, cortical calcifications, eye lesions, and arthrogryposis [46,47]. However, the mechanisms behind this pathology remain incompletely elucidated.…”

Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in fetal alcohol spectrum disorder

“…Craniofacial abnormalities have been deemed one of the most common classes of human birth defects by the World Health Organization and the cause of 1‐in‐3 of all congenital birth defects (Twigg & Wilkie, ; Shaw, ). Craniofacial malformations can be caused by genetic predispositions such as mutations in Fgf , Shh , and Bmp4 pathways (Graf, Malik, Hayano, & Mishina, ; Twigg et al, ; Twigg & Wilkie, ; Xavier et al, ), by viral infection as seen in Zika infections causing microcephaly (Kumar et al, ; Polonio, de Freitas, Zanluqui, & Peron, ), by malnutrition as seen in folic acid and vitamin A deficiency (VAD) causing cleft palate (Johansen, Lie, Wilcox, Andersen, & Drevon, ; Wilcox et al, ), and by exposure to teratogens, such as ethanol causing FASD (Jones & Smith, ). While the cause of craniofacial malformations might be different, the effect on the developing embryos is the same.…”