Human stem cell models to study host-virus interactions in the central nervous system

This Review by Harschnitz and Studer explains how human pluripotent stem cell technology can be used to explore antiviral immunity in the central nervous system. Such technology could help us to identify new therapies for a range of central nervous system viral infections and to uncover the mechanisms behind the central nervous system complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Advancements in human pluripotent stem cell technology offer a unique opportunity for the neuroimmunology field to study host-virus interactions directly in disease-relevant cells of the human central nervous system (CNS). Viral encephalitis is most commonly caused by herpesviruses, arboviruses and enteroviruses targeting distinct CNS cell types and often leading to severe neurological damage with poor clinical outcomes. Furthermore, different neurotropic viruses will affect the CNS at distinct developmental stages, from early prenatal brain development to the aged brain. With the unique flexibility and scalability of human pluripotent stem cell technology, it is now possible to examine the molecular mechanisms underlying acute infection and latency, determine which CNS subpopulations are specifically infected, study temporal aspects of viral susceptibility, perform high-throughput chemical or genetic screens for viral restriction factors and explore complex cell-non-autonomous disease mechanisms. Therefore, human pluripotent stem cell technology has the potential to address key unanswered questions about antiviral immunity in the CNS, including emerging questions on the potential CNS tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Automated summary

The review explains the use of human pluripotent stem cell technology in studying antiviral immunity in the central nervous system. This technology offers a unique opportunity for researching new therapies and mechanisms of CNS viral infections, including those associated with SARS-CoV-2. The advancements in this technology allow for studying host-virus interactions and complex disease mechanisms in disease-relevant cells of the human CNS.