Translational Neuroscience Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Exp Neurol. 2023 Sep;367:114469. doi: 10.1016/j.expneurol.2023.114469. Epub 2023 Jun 14.
Prenatal Zika virus (ZIKV) infection is a serious global concern as it can lead to brain injury and many serious birth defects, collectively known as congenital Zika syndrome. Brain injury likely results from viral mediated toxicity in neural progenitor cells. Additionally, postnatal ZIKV infections have been linked to neurological complications, yet the mechanisms driving these manifestations are not well understood. Existing data suggest that the ZIKV envelope protein can persist in the central nervous system for extended periods of time, but it is unknown if this protein can independently contribute to neuronal toxicity. Here we find that the ZIKV envelope protein is neurotoxic, leading to overexpression of poly adenosine diphosphate -ribose polymerase 1, which can induce parthanatos. Together, these data suggest that neuronal toxicity resulting from the envelope protein may contribute to the pathogenesis of post-natal ZIKV-related neurologic complications.
产前寨卡病毒(ZIKV)感染是一个严重的全球关注问题,因为它可导致脑损伤和许多严重的出生缺陷,统称为先天性寨卡综合征。脑损伤可能是由神经祖细胞中的病毒介导的毒性引起的。此外,产后寨卡病毒感染与神经并发症有关,但导致这些表现的机制尚不清楚。现有数据表明,寨卡病毒包膜蛋白可在中枢神经系统中持续存在很长时间,但尚不清楚该蛋白是否可以独立引起神经元毒性。在这里,我们发现寨卡病毒包膜蛋白具有神经毒性,导致多聚腺苷二磷酸核糖聚合酶 1 的过度表达,这可能诱导坏死性凋亡。总之,这些数据表明,包膜蛋白引起的神经元毒性可能导致产后寨卡病毒相关神经并发症的发病机制。