Human microglial models to study host-virus interactions
Rachel E McMillan1, Ellen Wang2, Aaron F Carlin3
1Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, United States of America; Department of Pathology and Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States of America.
Abstract:
Microglia, the resident macrophage of the central nervous system, are increasingly recognized as contributing to diverse aspects of human development, health, and disease. In recent years, numerous studies in both mouse and human models have identified microglia as a "double edged sword" in the progression of neurotropic viral infections: protecting against viral replication and cell death in some contexts, while acting as viral reservoirs and promoting excess cellular stress and cytotoxicity in others. It is imperative to understand the diversity of human microglial responses in order to therapeutically modulate them; however, modeling human microglia has been historically challenging due to significant interspecies differences in innate immunity and rapid transformation upon in vitro culture. In this review, we discuss the contribution of microglia to the neuropathogenesis of key neurotropic viral infections: human immunodeficiency virus 1 (HIV-1), Zika virus (ZIKV), Japanese encephalitis virus (JEV), West Nile virus (WNV), Herpes simplex virus (HSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We pay special attention to recent work with human stem cell-derived microglia and propose strategies to leverage these powerful models to further uncover species- and disease-specific microglial responses and novel therapeutic interventions for neurotropic viral infections.
Insights
Microglia play a dual role in neurotropic viral infections, acting as both protectors and facilitators of disease. Understanding human microglial responses is key to developing new therapies for viral infections of the brain.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Microglia, the central nervous system's immune cells, have a complex role in neurotropic viral infections.
- They can be protective or detrimental, acting as viral reservoirs and promoting neuroinflammation.
- Modeling human microglia is challenging due to interspecies differences and in vitro culture artifacts.
Conclusions:
- Accurate modeling of human microglia is crucial for understanding their role in neurotropic viral infections.
- Human stem cell-derived microglia represent a promising avenue for future research.
- Further investigation is needed to develop targeted therapeutic interventions for neurotropic viral diseases.
