Molecular Neurobiology

, Volume 55, Issue 5, pp 4160–4184 | Cite as

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

  • Gerwyn Morris
  • Tatiana Barichello
  • Brendon Stubbs
  • Cristiano A. Köhler
  • André F. Carvalho
  • Michael Maes


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.


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


Compliance with Ethical Standards

We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Authors AFC and MM contributed equally as senior authors of this review article.

Author’s Contributions

All authors had contributed to the design and writing of this manuscript. Its final version was read and approved by all authors.

Conflict of Interest

The authors declare that they have no conflict of interest.


There was no specific funding for this specific study.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Tir Na NogLlanelliUK
  2. 2.Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences UnitUniversity of Southern Santa Catarina (UNESC)CriciúmaBrazil
  3. 3.Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical SchoolThe University of Texas Health Science Center at Houston (UTHealth)HoustonUSA
  4. 4.Neuroscience Graduate ProgramThe University of Texas Graduate School of Biomedical Sciences at HoustonHoustonUSA
  5. 5.Physiotherapy Department, South London and Maudsley NHS Foundation TrustLondonUK
  6. 6.Health Service and Population Research Department, Institute of Psychiatry, Psychology and NeuroscienceKing’s College LondonLondonUK
  7. 7.Faculty of Health, Social Care and EducationAnglia Ruskin UniversityChelmsfordUK
  8. 8.Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of MedicineFederal University of CearáFortalezaBrazil
  9. 9.IMPACT Strategic Research Centre, School of Medicine, Barwon HealthDeakin UniversityGeelongAustralia
  10. 10.Health Sciences Postgraduate Program, Health Sciences CenterState University of LondrinaLondrinaBrazil
  11. 11.Department of Psychiatry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  12. 12.RevitalisWaalreThe Netherlands
  13. 13.Department of PsychiatryMedical University of PlovdivPlovdivBulgaria

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