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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.

Author information

1
Tir Na Nog, Bryn Road seaside 87, Llanelli, Wales, SA15 2LW, UK.
2
Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
3
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.
4
Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
5
Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK.
6
Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.
7
Faculty of Health, Social Care and Education, Anglia Ruskin University, Bishop Hall Lane, Chelmsford, CM1 1SQ, UK.
8
Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
9
IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, 3220, Australia. dr.michaelmaes@hotmail.com.
10
Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Parana, Brazil. dr.michaelmaes@hotmail.com.
11
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. dr.michaelmaes@hotmail.com.
12
Revitalis, Waalre, The Netherlands. dr.michaelmaes@hotmail.com.
13
Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria. dr.michaelmaes@hotmail.com.

Abstract

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.

KEYWORDS:

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

PMID:
28601976
DOI:
10.1007/s12035-017-0635-y
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