The role of microglia in viral encephalitis: A review

Abstract

Viral encephalitis is still very prominent around the world, and traditional antiviral therapies still have shortcomings. Some patients cannot get effective relief or suffer from serious sequelae. At present, people are studying the role of the innate immune system in viral encephalitis. Microglia, as resident cells of the central nervous system (CNS), can respond quickly to various CNS injuries including trauma, ischemia, and infection and maintain the homeostasis of CNS, but this response is not always good; sometimes, it will exacerbate damage. Studies have shown that microglia also act as a double-edged sword during viral encephalitis. On the one hand, microglia can sense ATP signals through the purinergic receptor P2Y12 and are recruited around infected neurons to exert phagocytic activity. Microglia can exert a direct antiviral effect by producing type 1 interferon (IFN-1) to induce IFN-stimulated gene (ISG) expression of themselves or indirect antiviral effects by IFN-1 acting on other cells to activate corresponding signaling pathways. In addition, microglia can also exert an antiviral effect by inducing autophagy or secreting cytokines. On the other hand, microglia mediate presynaptic membrane damage in the hippocampus through complement, resulting in long-term memory impairment and cognitive dysfunction in patients with encephalitis. Microglia mediate fetal congenital malformations caused by Zika virus (ZIKV) infection. The gene expression profile of microglia in HIV encephalitis changes, and they tend to be a pro-inflammatory type. Microglia inhibited neuronal autophagy and aggravated the damage of CNS in HIV encephalitis; E3 ubiquitin ligase Pellino (pelia) expressed by microglia promotes the replication of virus in neurons. The interaction between amyloid-β peptide (Aβ) produced by neurons and activated microglia during viral infection is uncertain. Although neurons can mediate antiviral effects by activating receptor-interacting protein kinases 3 (RIPK3) in a death-independent pathway, the RIPK3 pathway of microglia is unknown. Different brain regions have different susceptibility to viruses, and the gene expression of microglia in different brain regions is specific. The relationship between the two needs to be further confirmed. How to properly regulate the function of microglia and make it exert more anti-inflammatory effects is our next research direction.