Abstract
The 2015-2016 Zika virus (ZIKV) outbreak in Brazil was remarkably linked to the incidence of microcephaly and other deleterious clinical manifestations, including eye abnormalities, in newborns. It is known that ZIKV targets the placenta, triggering an inflammatory profile that may cause placental insufficiency. Transplacental lipid transport is delicately regulated during pregnancy and deficiency on the delivery of lipids such as arachidonic and docosahexaenoic acids may lead to deficits in both brain and retina during fetal development. Here, plasma lipidome profiles of ZIKV exposed microcephalic and normocephalic newborns were compared to non-infected controls. Our results reveal major alterations in circulating lipids from both ZIKV exposed newborns with and without microcephaly relative to controls. In newborns with microcephaly, the plasma concentrations of hydroxyoctadecadienoic acid (HODE), primarily as 13-HODE isomer, derived from linoleic acid were higher as compared to normocephalic ZIKV exposed newborns and controls. Total HODE concentrations were also positively associated with levels of other oxidized lipids and several circulating free fatty acids in newborns, indicating a possible plasma lipidome signature of microcephaly. Moreover, higher concentrations of lysophosphatidylcholine in ZIKV exposed normocephalic newborns relative to controls suggest a potential disruption of polyunsaturated fatty acids transport across the blood-brain barrier of fetuses. The latter data is particularly important given the neurocognitive and neurodevelopmental abnormalities observed in follow-up studies involving children with antenatal ZIKV exposure, but normocephalic at birth. Taken together, our data reveal that plasma lipidome alterations associated with antenatal exposure to ZIKV could contribute to identification and monitoring of the wide spectrum of clinical phenotypes at birth and further, during childhood.
Highlights
Exposure of newborns to Zika virus (ZIKV) during pregnancy has been linked to congenital ZIKV syndrome (CZS), resulting in severe neurodevelopmental abnormalities in infants, most prominently microcephaly, with other associated clinical presentations such as seizures, hearing and visual abnormalities, dysphagia and fetal death [1,2,3,4,5,6]
A total of 30 participants belonging to three groups were enrolled: control/ healthy newborns without antenatal ZIVK exposure, 9 normocephalic newborns exposed to ZIKV and newborns with ZIKV-induced microcephaly
Major lipid pools were represented by cholesteryl esters (CE), followed by triglycerides (TG), phosphatidylcholine, sphingomyelin and free fatty acids (FFA), and displayed a considerable variation in lipid concentrations within groups (S1A Fig)
Summary
Neurodevelopmental abnormalities manifested in the early childhood Stratification of these clinical phenotypes in newborns with suspected antenatal ZIKV exposure is challenging, but critical to improve early assessment of rehabilitative interventions. Plasma lipidome profiling of 274 lipid species was performed in both normocephalic and microcephalic newborns with antenatal ZIKV exposure and compared to noninfected controls. Microcephaly was strongly associated with an oxidized free fatty acid and ZIKV exposed normocephalic newborns exhibited higher plasma concentrations of lysophosphatidylcholine relative to controls. These findings emphasize the need for studies focused on the role of individual lipids in neuropathogenesis of ZIKV and raise the potential of plasma lipidome profiling for early diagnosis of newborns with suspected antenatal ZIKV exposure. To validate the predictive ability of this approach, prospective studies with a larger cohort of newborns are required
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