Understanding the Role of Antiviral Cytokines and Chemokines on Neural Stem/Progenitor Cell Activity and Survival

Abstract

Viral infections of the central nervous system are accompanied by the expression of cytokines and chemokines that can be critical for the control of viral replication in the brain. The outcomes of cytokine/chemokine signaling in neural cells vary widely, with cell-specific effects on cellular activity, proliferation, and survival. Neural stem/progenitor cells (NSPCs) are often altered during viral infections, through direct infection by the virus or by the influence of immune cell activity or cytokine/chemokine signaling. However, it has been challenging to dissect the contribution of the virus and specific inflammatory mediators during an infection. In addition to initiating an antiviral program in infected NSPCs, cytokines/chemokines can induce multiple changes in NSPC behavior that can perturb NSPC numbers, differentiation into other neural cells, and migration to sites of injury, and ultimately brain development and repair. The focus of this review was to dissect the effects of common antiviral cytokines and chemokines on NSPC activity, and to consider the subsequent pathological consequences for the host from changes in NSPC function.

Neural Stem Cells: What Happens When They Go Viral?

“…In addition to the virus, antiviral cytokines and chemokines can also disrupt NSC differentiation [ 15 ]. Chemokines orchestrate the movement of immune cells to the site of injury or infection, and chemokine receptors are often expressed on NSCs [ 95 ].…”

“…NSCs may be directly infected by viruses, leading to changes in commitment to other cell types and potentially cell death. NSCs can also be affected by cytokines and chemokines that are released as part of the antiviral immune response [ 15 , 16 , 17 ]. It has been complicated to dissect the contribution of the viral infection and the antiviral immune response in mediating NSC activity, but recent in vitro and in vivo studies have shed light onto how NSCs respond to viruses.…”

The Role of FoxG1 in the Inner Ear

“…Neural stem cells (NSCs) are self-renewable multipotent cells that can differentiate into different types of nerve cells ( Chandwani et al, 2019 ). Because neural progenitor cells (NPCs) have limited life span and poor self-renewal ability, NSCs regulate the balance of pro-death and pro-survival signals to ensure the number of progenitor cell pools during development ( Yadirgi et al, 2011 ; Sierra et al, 2015 ).…”

FOXG1 Dose in Brain Development

“…In the developing brain, neural stem cells (NSCs) are controlled by a tightly regulated series of signals that coordinate proliferation and differentiation into different neural cell types (neurons, astrocytes, and oligodendrocytes) that ultimately populate the mature brain (67). NSCs are defined as self-renewing, multipotent cells that generate neurons, astrocytes, and oligodendrocytes.…”

“…Neural progenitor cells (NPCs) have a limited life span, less self-renewal capacity, and may be multipotent or unipotent (68, 69). Subventricular zone NSCs first divide symmetrically to expand the population of ventricular zone progenitor cells then switch to divide asymmetrically (67). Asymmetric cell division gives rise to a progenitor cell and radial glia or neurons which migrate and form the cortical layers.…”