Neurotropic and Zoonotic Viruses: Pathogenesis, Host Responses, and Vaccine Innovations

The ability of zoonotic viruses to breach the central nervous system represents one of the most dangerous and poorly understood aspects of viral pathogenesis. Viruses such as rabies virus, Nipah virus, and West Nile virus have evolved distinct molecular strategies to cross the blood–brain barrier, exploit neuronal architecture, and establish infection within the CNS — often with devastating and irreversible clinical consequences. Despite progress in structural and molecular virology, the precise cellular and molecular events that permit neuroinvasion remain incompletely defined. Understanding how zoonotic viruses engage host receptors at the neural interface, subvert barrier defenses, and navigate axonal and trans-synaptic routes into the brain is essential for identifying targetable vulnerabilities in the infection process.

This Research Topic focuses specifically on the molecular and cellular mechanisms by which zoonotic viruses invade the central nervous system. It seeks to bring together molecular virologists, cell biologists, and neuroscientists to define the virus–host interactions that govern neurotropism and neuroinvasion, from initial peripheral receptor engagement to establishment of CNS infection. By concentrating on this critical step in pathogenesis, the collection aims to generate mechanistic insights that can directly inform the development of entry-targeted antivirals and neuroprotective strategies.

The scope is restricted to studies investigating the cellular and molecular basis of neuroinvasion. Research addressing systemic replication, general immune evasion outside the CNS context, vaccine efficacy, or clinical/epidemiological outcomes without mechanistic insight into CNS entry is outside the remit of this RT.

We welcome original research and review articles addressing, but not limited to, the following themes:

- Viral surface proteins and host receptor engagement that determine neurotropism and CNS entry

- Blood–brain barrier disruption — molecular interactions between viral components and endothelial tight junctions, transcytosis mechanisms, and paracellular entry routes

- Axonal transport and trans-synaptic spread as routes of CNS invasion

- Neuronal and glial cell tropism — receptor distribution, intracellular trafficking, and permissiveness of specific CNS cell types

- Peripheral nervous system as a gateway — mechanisms of retrograde axonal transport from the infection site to the CNS

- Host restriction and susceptibility factors at the neural barrier and within CNS cells

- In vitro and in vivo models of neuroinvasion with direct translational relevance to human CNS infection

- Comparative neuroinvasion strategies across zoonotic virus families to identify shared and virus-specific mechanisms