The multitaskers of the brain: Glial responses to viral infections and associated post‐infectious neurologic sequelae

Abstract

Many viral infections cause acute and chronic neurologic diseases which can lead to degeneration of cortical functions. While neurotropic viruses that gain access to the central nervous system (CNS) may induce brain injury directly via infection of neurons or their supporting cells, they also alter brain function via indirect neuroimmune mechanisms that may disrupt the blood-brain barrier (BBB), eliminate synapses, and generate neurotoxic astrocytes and microglia that prevent recovery of neuronal circuits. Non-neuroinvasive, neurovirulent viruses may also trigger aberrant responses in glial cells, including those that interfere with motor and sensory behaviors, encoding of memories and executive function. Increasing evidence from human and animal studies indicate that neuroprotective antiviral responses that amplify levels of innate immune molecules dysregulate normal neuroimmune processes, even in the absence of neuroinvasion, which may persist after virus is cleared. In this review, we discuss how select emerging and re-emerging RNA viruses induce neuroimmunologic responses that lead to dysfunction of higher order processes including visuospatial recognition, learning and memory, and motor control. Identifying therapeutic targets that return the neuroimmune system to homeostasis is critical for preventing virusinduced neurodegenerative disorders.

Live-attenuated Japanese encephalitis virus inhibits glioblastoma growth and elicits potent antitumor immunity

“…Moreover, the CNS in a stable state has been examined immunologically ( 23 , 24 ). After infection in the CNS, the interaction between infiltrating T cells and activated microglia can maintain the function of T effector cells in CNS parenchyma ( 23 , 25 ). Thus, these findings support that although the brain is a different part of immunology, the immune microenvironment provides sufficient opportunities for immunotherapy for the treatment of brain tumors.…”

Immunopathology of herpes simplex virus‐associated neuroinflammation: Unveiling the mysteries

“…Furthermore, HSV-1 infections within the brain, regardless of symptomatic or asymptomatic presentations, can incite neuronal damage and ultimately contribute to the onset of NDs. 44,[56][57][58]…”

“…HSV‐1 can potentially induce SANE, a condition marked by heightened neuroinflammation and prolonged neuroimmune activation, posing a life‐threatening scenario. Furthermore, HSV‐1 infections within the brain, regardless of symptomatic or asymptomatic presentations, can incite neuronal damage and ultimately contribute to the onset of NDs 44,56–58 …”

DYT-TOR1A dystonia: an update on pathogenesis and treatment

“…In addition to traditional treatment methods such as medication, surgery, and BoNT therapy, there are also some emerging treatment methods being researched and explored for DYT- TOR1A dystonia, including (1) optogenetic therapy, which is a gene therapy technique that uses photosensitive proteins and laser light to control neuron activity ( Richter et al, 2019 ; Sciamanna et al, 2020 ; Schulz et al, 2023 ); (2) neuroprotective agents, which can protect nerve cells from damage or death, thereby reducing disease symptoms; (3) immunotherapy, which utilizes the immune system to identify and attack diseased cells ( Dave and Klein, 2023 ); and (4) cell therapy, which uses human cells or other types of cells to repair or replace damaged tissues and cells. Although these emerging treatment methods are still in the research and exploration stage, they may bring new breakthroughs and hope for the treatment of DYT- TOR1A dystonia ( Cruz et al, 2020 ; Stengel et al, 2020 ; Akter et al, 2021 ; Tang et al, 2021 ).…”