Zika Virus as an Emerging Neuropathogen: Mechanisms of Neurovirulence and Neuro-Immune Interactions
Gerwyn Morris1, Tatiana Barichello2,3,4, Brendon Stubbs5,6,7
1Tir Na Nog, Bryn Road seaside 87, Llanelli, Wales, SA15 2LW, UK.
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.
Insights
Zika virus (ZIKV) evolution has led to neurovirulent strains, causing microcephaly and Guillain-Barre syndrome. Understanding ZIKV neuro-immune interactions is key for developing vaccines and therapies.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Zika virus (ZIKV), an arbovirus, rapidly spread globally, causing febrile illness.
- ZIKV infection is linked to severe neurological conditions, including congenital Zika virus syndrome (microcephaly) and Guillain-Barre syndrome.
- Evidence suggests the emergence of more neurovirulent ZIKV strains from less pathogenic predecessors.
Purpose of the Study:
- To critically discuss genetic and structural viral alterations contributing to ZIKV neurovirulence.
- To elucidate the neuro-immune mechanisms underlying ZIKV-associated neuropathology.
- To identify avenues for vaccine development and therapeutic strategies against ZIKV.
Main Methods:
- Review of existing literature on ZIKV genetics, structure, and pathogenesis.
- Analysis of host-pathogen interactions in the context of ZIKV-induced neurological diseases.
- Discussion of recent advancements in ZIKV research.
Main Results:
- Potential genetic and structural viral changes may explain the rise of neurovirulent ZIKV strains.
- A mechanistic framework for ZIKV-related neuro-immune responses is proposed.
- Recent findings highlight potential pathways for vaccine and therapeutic development.
Conclusions:
- Mechanisms of ZIKV neurovirulence and associated neuro-immune interactions require further elucidation.
- Development of effective vaccines and therapies faces significant challenges.
- A proposed research agenda aims to address current knowledge gaps in ZIKV neuropathogenesis.
