# Modeling Virus-Associated Central Nervous System Disease in Non-Human Primates

## TL;DR

This paper reviews how non-human primates can be used to study virus-related central nervous system diseases caused by both neurotropic and non-neurotropic viruses.

## Contribution

The paper provides a comprehensive review of NHP models for viruses that impact the CNS, emphasizing translational relevance to human disease.

## Key findings

- NHP models closely mirror human CNS disease pathogenesis and immune responses.
- Viruses like West Nile, Zika, and HIV are studied in NHPs to understand their effects on the CNS.
- NHP models allow for better understanding of disease progression and therapeutic interventions.

## Abstract

While viral pathogens are often subdivided into neurotropic and non-neurotropic categories, systemic inflammation caused by non-neurotropic viruses still possesses the ability to alter the central nervous system (CNS). Studies of CNS disease induced by viral infection, whether neurotropic or not, are presented with a unique set of challenges. First, because brain biopsies are rarely necessary to diagnose viral-associated neurological disorders, antemortem tissue samples are not readily available for study and human pathological studies must rely on end-stage, postmortem evaluations. Second, in vitro models fail to fully capture the nuances of an intact immune system, necessitating the use of animal models to fully characterize pathogenesis and identify potential therapeutic approaches. Non-human primates (NHP) represent a particularly attractive animal model in that they overcome many of the limits posed by more distant species and most closely mirror human disease pathogenesis and susceptibility. Here, we review NHP infection models of viruses known to infect and/or replicate within cells of the CNS, including West Nile virus, the equine encephalitis viruses, Zika virus, and herpesviruses, as well as those known to alter the immune status of the brain in the absence of significant CNS penetrance, including human immunodeficiency virus (HIV) in the current era of combination antiretroviral therapy (cART) and the coronavirus of severe acute respiratory syndrome (SARS)-CoV−2. This review focuses on viruses with an established role in causing CNS disease, including encephalitis, meningitis, and myelitis and NHP models of viral infection that are directly translatable to the human condition through relevant routes of infection, comparable disease pathogenesis, and responses to therapeutic intervention.