Neuropathology of Zika Virus Infection
Isaac H Solomon1, Danny A Milner1, Rebecca D Folkerth1
1Department of Pathology, Brigham and Women's Hospital, Boston, USA.
Abstract:
Zika virus (ZIKV) is a member of the Flaviviridae family that had been associated only with mild disease prior to the 2015 outbreak in Brazil. A dramatic increase in reported cases of microcephaly and Guillain-Barré syndrome during this time prompted significant research into possible associations with ZIKV and its neurotropic properties. Infection of neural progenitor cells and organoids have been shown to induce apoptosis and dysregulation of growth, and mouse studies have demonstrated viral replication in brain tissue in adults, as well as vertical transmission resulting in embryonic brain abnormalities. Large case series of clinical and radiological findings of congenital ZIKV infection have begun to be published; however, pathology reports have been limited to two case reports and two small case series. Thus far, the findings have largely been restricted to the brain and include diffuse grey and white matter involvement consisting of dystrophic calcifications, gliosis, microglial nodules, neuronophagia, and scattered lymphocytes. Mild chronic villitis was observed in the placental tissue in some cases, and the remaining organs were essentially uninvolved. Larger, systematic studies, including correlation of histological findings with gestational age at the time of maternal infection, will be required to determine the full range of Zika virus-induced abnormalities and to help guide future clinical decision making.
Insights
Zika virus (ZIKV) infection can cause severe brain abnormalities in fetuses, leading to microcephaly. Further research is needed to understand the full spectrum of ZIKV-related congenital abnormalities and guide clinical care.
Area of Science:
- Virology
- Neuroscience
- Pathology
Background:
- Zika virus (ZIKV), a Flaviviridae family member, was previously associated with mild illness.
- The 2015 Brazil outbreak linked ZIKV to increased microcephaly and Guillain-Barré syndrome cases, highlighting its neurotropic potential.
- Previous studies showed ZIKV's impact on neural cells and embryonic brain development in mice.
Purpose of the Study:
- To review and synthesize existing pathology reports on congenital Zika virus infection.
- To identify the range of ZIKV-induced neuropathological findings in infants.
- To highlight the need for larger, systematic studies correlating maternal infection timing with fetal outcomes.
Main Methods:
- Review of limited existing pathology reports and case series on congenital ZIKV infection.
- Analysis of clinical and radiological findings from large case series.
- Histopathological examination of affected fetal tissues, including brain and placenta.
Main Results:
- ZIKV infection primarily affects the brain, causing diffuse grey and white matter abnormalities.
- Observed neuropathological findings include calcifications, gliosis, microglial nodules, neuronophagia, and inflammation.
- Placental involvement was minimal, with mild chronic villitis noted in some cases; other organs were largely unaffected.
Conclusions:
- Congenital ZIKV infection leads to significant neuropathology, primarily impacting brain development.
- Current pathology data is limited, necessitating larger systematic studies.
- Correlating histological findings with gestational age is crucial for understanding the full spectrum of ZIKV teratogenicity and informing clinical management.
