Zika infection and the development of neurological defects

Abstract

SummaryStarting with the outbreak in Brazil, Zika virus (ZIKV) infection has been correlated with severe syndromes such as congenital Zika syndrome and Guillain-Barré syndrome. Here, we review the status of Zika virus pathogenesis in the central nervous system (CNS). One of the main concerns about ZIKV exposure during pregnancy is abnormal brain development, which results in microcephaly in newborns. Recent advances in in vitro research show that ZIKV can infect and obliterate cells from the CNS, such as progenitors, neurons, and glial cells. Neural progenitor cells seem to be the main target of the virus, with infection leading to less cell migration, neurogenesis impairment, cell death and, consequently, microcephaly in newborns. The downsizing of the brain can be directly associated with defective development of the cortical layer. In addition, in vivo investigations in mice reveal that ZIKV can cross the placenta and migrate to fetuses, but with a significant neurotropism, which results in brain damage for the pups. Another finding shows that hydrocephaly is an additional consequence of ZIKV infection, being detected during embryonic and fetal development in mouse, as well as after birth in humans. In spite of the advances in ZIKV research in the last year, the mechanisms underlying ZIKV infection in the CNS require further investigation particularly as there are currently no treatments or vaccines against ZIKV infection.

Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection

“…We lastly sought to apply the organoid system towards modeling and ameliorating neurodevelopmental diseases such as microcephaly resulting from ZIKV infection, collectively termed congenital Zika Syndrome (CZS) (Russo et al, 2017). ZIKV envelope protein (E) was readily detected in many cortical cells 3 days post infection (3 dpi) of organoids with a Puerto Rican ZIKV isolate (PRVABC 59), mostly in the VZ and SVZ regions (Figures 5A and S7F).…”

Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques

“…The majority of research in newborns and infants has to date focused on the congenital ZIKV syndrome (1-3, 49), leaving the outcome of early postnatal infection on the developing infant brain uncertain. Reports of microcephaly developing after birth with congenital ZIKV infection (50, 51) suggest that the postnatal insult of ZIKV to the developing brain can be severe.…”

Long-term alterations in brain and behavior after postnatal Zika virus infections in infant macaques

“…The current study demonstrates that ZIKV infection during the early postnatal period can have long lasting impact on brain structure, function, behavior, and cognition in primates. To date, most research has focused on congenital ZIKV syndrome [4][5][6]56 , leaving many questions unanswered about the potential impact of postnatal infection on the developing brain. Given the protracted development of the brain in humans and nonhuman primates, there is considerable opportunity for plasticity and functional compensation after early brain damage.…”