Neurotoxic properties of the Zika virus envelope protein

Joseph P. Steiner, Translational Neuroscience Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Muznabanu Bachani, Translational Neuroscience Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Nasir Malik, Translational Neuroscience Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Wenxue Li, Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Richa Tyagi, Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Kevon Sampson, Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Rachel P. Abrams, Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Youssef Kousa, Division of Neurology, Children's National Hospital, Washington, DC 20010, USA; Department of Genomics and Precision Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
Jamie Solis, Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Tory P. Johnson, Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.
Avindra Nath, 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. Electronic address: natha@ninds.nih.gov.

Document Type

Journal Article

Publication Date

6-14-2023

Journal

Experimental neurology

Volume

367

DOI

10.1016/j.expneurol.2023.114469

Keywords

Envelope protein; Neurological complications; Neurotoxicity; Poly adenosine diphosphate -ribose polymerase 1; Zika virus

Abstract

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.

Department

Neurology

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