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Mol Neurobiol. 2017 Jun 11. doi: 10.1007/s12035-017-0635-y. [Epub ahead of print]

Zika Virus as an Emerging Neuropathogen: Mechanisms of Neurovirulence and Neuro-Immune Interactions.

Morris G1, Barichello T2,3,4, Stubbs B5,6,7, Köhler CA8, Carvalho AF8, Maes M9,10,11,12,13.

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Tir Na Nog, Bryn Road seaside 87, Llanelli, Wales, SA15 2LW, UK.
Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK.
Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.
Faculty of Health, Social Care and Education, Anglia Ruskin University, Bishop Hall Lane, Chelmsford, CM1 1SQ, UK.
Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, 3220, Australia.
Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Parana, Brazil.
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Revitalis, Waalre, The Netherlands.
Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria.


Zika virus (ZIKV) is an emerging arbovirus of the genus Flaviviridae, which causes a febrile illness and has spread from across the Pacific to the Americas in a short timeframe. Convincing evidence has implicated the ZIKV to incident cases of neonatal microcephaly and a set of neurodevelopmental abnormalities referred to as the congenital Zika virus syndrome. In addition, emerging data points to an association with the ZIKV and the development of the so-called Guillain-Barre syndrome, an acute autoimmune polyneuropathy. Accumulating knowledge suggests that neurovirulent strains of the ZIKV have evolved from less pathogenic lineages of the virus. Nevertheless, mechanisms of neurovirulence and host-pathogen neuro-immune interactions remain incompletely elucidated. This review provides a critical discussion of genetic and structural alterations in the ZIKV which could have contributed to the emergence of neurovirulent strains. In addition, a mechanistic framework of neuro-immune mechanisms related to the emergence of neuropathology after ZIKV infection is discussed. Recent advances in knowledge point to avenues for the development of a putative vaccine as well as novel therapeutic strategies. Nevertheless, there are unique unmet challenges that need to be addressed in this regard. Finally, a research agenda is proposed.


Autoimmunity; Cytokines; Guillain-Barre syndrome; Microcephaly; Neurodevelopment; Neurology; Perinatal infection; Psychiatry; Zika virus

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