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.