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Published on: October 17, 2018
Correlation between Apoptosis and in Situ Immune Response in Fatal Cases of Microcephaly Caused by Zika Virus
Jorge R de Sousa1, Raimunda S S Azevedo1, Arnaldo J Martins Filho2
1Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil.
Abstract:
Zika virus (ZIKV) is a single-stranded positive-sense RNA flavivirus that possesses a genome approximately 10.7 Kb in length. Although pro-inflammatory and anti-inflammatory cytokines and apoptotic markers belonging to the extrinsic and intrinsic pathways are suggested to be involved in fatal cases of ZIKV-induced microcephaly, their exact roles and associations are unclear. To address this, brain tissue samples were collected from 10 individuals, five of whom were diagnosed as ZIKV positive with microcephaly and a further five were flavivirus-negative controls that died because of other causes. Examination of material from the fatal cases of microcephaly revealed lesions in the cerebral cortex, edema, vascular proliferation, neuronal necrosis, gliosis, neuronophagy, calcifications, apoptosis, and neuron loss. The expression of various apoptosis markers in the neural parenchyma, including FasL, FAS, BAX, BCL2, and caspase 3 differed between ZIKV-positive cases and controls. Further investigation of type 1 and 2 helper T-cell cytokines confirmed a greater anti-inflammatory response in fatal ZIKV-associated microcephaly cases. Finally, an analysis of the linear correlation between tumor necrosis factor-α, IL-1β, IL-4, IL-10, transforming growth factor-β, and IL-33 expression and various apoptotic markers suggested that the immune response may be associated with the apoptotic phenomenon observed in ZIKV-induced microcephaly.
Insights
Zika virus (ZIKV) infection in fatal microcephaly cases shows distinct brain lesions and altered apoptosis markers. An anti-inflammatory immune response correlates with these apoptotic changes, suggesting a link between immunity and ZIKV-induced microcephaly.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Zika virus (ZIKV) is a flavivirus implicated in microcephaly, but the underlying mechanisms involving cytokines and apoptosis remain unclear.
- Fatal ZIKV-associated microcephaly cases exhibit specific neuropathological features.
Purpose of the Study:
- To investigate the roles of apoptotic markers and cytokines in ZIKV-induced fatal microcephaly.
- To explore the association between immune responses and apoptotic phenomena in ZIKV-positive microcephaly.
Main Methods:
- Comparative analysis of brain tissue from ZIKV-positive microcephaly cases (n=5) and flavivirus-negative controls (n=5).
- Assessment of neuropathological lesions, expression of apoptosis markers (FasL, FAS, BAX, BCL2, caspase 3), and T-cell cytokines (TNF-α, IL-1β, IL-4, IL-10, TGF-β, IL-33).
Main Results:
- ZIKV-positive cases showed cerebral cortex lesions, edema, vascular changes, neuronal necrosis, gliosis, neuronophagy, calcifications, apoptosis, and neuron loss.
- Differential expression of apoptosis markers (FasL, FAS, BAX, BCL2, caspase 3) was observed between ZIKV-positive and control groups.
- A heightened anti-inflammatory cytokine profile (IL-4, IL-10, TGF-β) was noted in fatal ZIKV-associated microcephaly, correlating with apoptotic markers.
Conclusions:
- Zika virus infection in fatal microcephaly is associated with significant neuropathology and altered apoptosis.
- The observed anti-inflammatory immune response in ZIKV-positive microcephaly cases may contribute to the apoptotic processes.
- Immune responses, particularly involving specific cytokines, are potentially linked to the pathogenesis of ZIKV-induced microcephaly.
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