Roles of HSV-1 infection-induced microglial immune responses in CNS diseases: friends or foes?
Abstract
Microglia, as brain-resident macrophages, are the first line of defense against brain invading pathogens. Further, their dysfunction has been recognized to be closely associated with mounting CNS diseases. Of note, chronic HSV-1 infection leads to the persistent activation of microglia, which elicit a comprehensive response by generating certain factors with neurotoxic and neuroprotective effects. CNS infection with HSV-1 results in herpes simplex encephalitis and herpes simplex keratitis. Microglial immune response plays a crucial role in the development of these diseases. Moreover, HSV-1 infection is strongly associated with several CNS diseases, especially Alzheimer's disease and schizophrenia. These CNS diseases can be effectively ameliorated by eliciting an appropriate immune response, such as inhibition of microglial proliferation and activation. Therefore, it is crucial to reassess the positive and negative roles of microglia in HSV-1 CNS infection for a more comprehensive and detailed understanding of the relationship between microglia and CNS diseases. Hence, the present review focuses on the dual roles of microglia in mediating HSV-1 CNS infection, as well as on the strategy of targeting microglia to ameliorate CNS diseases. Further research in this field can help comprehensively elucidate the dual role of the microglial immune response in HSV-1 CNS infection, providing a theoretical basis for identifying therapeutic targets against overactive microglia in CNS diseases and HSV-1 infection.
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Chronic HSV-1 infection induces persistent microglial activation, inducing antiviral IFN-β expression and generating neurotoxic factors such as ROS, TNF and NO, and chronic microglial activation triggers a vicious cycle of CNS inflammation.
“Additionally, chronic HSV-1 infection induced persistent microglial activation, consequently inducing antiviral IFN-β expression, while also generating neurotoxic factors, such as ROS, TNF and NO. ATP and MMP3 released from damaged neurons then acts to further activate microglia. Together, chronic activation of microglia mediated by HSV-1 infection triggers a vicious cycle of CNS inflammation [535”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [535]
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- Authors
- Wang, Y., Jia, J., Wang, Y., Li, F., Song, X., Qin, S., Wang, Z., Kitazato, K., & Wang, Y.
- Affiliations
- Jinan University (CN)
- Nagasaki University (JP)
- Corresponding author
- Kitazato, Kaio
- Wang, Yifei
- Venue
- Critical Reviews in Microbiology
- Publisher
- Informa UK Limited
- Published
- 2019-09-12
- Volume
- 45
- Issue
- 5-6
- Pages
- 581-594
- ISSN
- 1040-841X (ISSN-L)
- 1549-7828
- OpenAlex
- W2972564612
- Cited by
- 40
- References
- 129
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 3
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Critical Reviews in Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- herpes simplex virus type 1, microglia, microglial activation, neuroinflammation, herpes simplex encephalitis, herpes simplex keratitis, Alzheimer's disease, schizophrenia, neuroprotection, neurotoxicity, central nervous system infection
- MeSH terms
- Animals, Humans, Microglia, Herpesvirus 1, Human, Encephalitis, Herpes Simplex
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