Abstract
The global public health concern is heightened over the increasing number of emerging viruses, i.e., newly discovered or previously known that have expanded into new geographical zones. These viruses challenge the health-care systems in sub-Saharan Africa (SSA) countries from which several of them have originated and been transmitted by insects worldwide. Some of these viruses are neuroinvasive, but have been relatively neglected by neuroscientists. They may provide experiments by nature to give a time window for exposure to a new virus within sizeable, previously non-infected human populations, which, for instance, enables studies on potential long-term or late-onset effects on the developing nervous system. Here, we briefly summarize studies on the developing brain by West Nile, Zika, and Chikungunya viruses, which are mosquito-borne and have spread worldwide out of SSA. They can all be neuroinvasive, but their effects vary from malformations caused by prenatal infections to cognitive disturbances following perinatal or later infections. We also highlight Ebola virus, which can leave surviving children with psychiatric disturbances and cause persistent infections in the non-human primate brain. Greater awareness within the neuroscience community is needed to emphasize the menace evoked by these emerging viruses to the developing brain. In particular, frontline neuroscience research should include neuropediatric follow-up studies in the field on long-term or late-onset cognitive and behavior disturbances or neuropsychiatric disorders. Studies on pathogenetic mechanisms for viral-induced perturbations of brain maturation should be extended to the vulnerable periods when neurocircuit formations are at peaks during infancy and early childhood.
Highlights
Exposure to infections during the first part of fetal life, the so-called teratogenic window, can cause severe brain malformations
By comparing four neuroinvasive infections originating from sub-Saharan Africa (SSA), i.e., Zika virus (ZIKV), West Nile virus (WNV), Chikungunya virus (CHIKV), and Ebola virus (EBOV), we find that they attack the human brain at various stages of development
We present evidence that various spectra of neurodevelopmental disturbances may be associated with the emerging viral infections: ZIKV with congenital microcephaly following intrauterine infections, and postnatal brain alterations with or without microcephaly; CHIKV with postnatal microcephaly following perinatal infections, and behavior and communication disturbances; WNV with cognitive dysfunctions following infections mostly in adults, but infant/childhood infections are underestimated and need further studies
Summary
Exposure to infections during the first part of fetal life, the so-called teratogenic window, can cause severe brain malformations. Cognitive impairments and behavioral disturbances in children born to HIV-infected mothers [4] or subjected to childhood malaria [5] have been described in SSA; unprovoked late-onset epilepsy may occur following the latter infection [6]. Of particular concern to African neuroscience are emerging viral infections. They can reveal associations between infections and rare sequelae in human populations, as poliomyelitis once did for “infantile paralysis” [7]. Life viral infections may, in one way or the other, be implied in the pathogenesis of cognitive and neuropsychiatric disturbances: the “neurodevelopmental hypothesis” for late-onset brain dysfunctions [e.g., Ref. Time windows for viral invasions, given by occurrence of the emerging epidemics, may reveal unique associations between viral infections and late-onset human brain disturbances
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