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Cited by 10Neuroinflammation and Neurodegeneration MechanismsAnimal Virus Infections Studiesinterferon and immune responses

Evidence of Microglial Immune Response Following Coronavirus PHEV Infection of CNS

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Zhang, Jing, Li, Zi, Lu, Huijun, Shi, Junchao, Gao, Rui, Ma, Ying, Lan, Yungang, Guan, Jiyu +3 more·2022·Frontiers in Immunology
DOI 10.3389/fimmu.2021.804625PMC PMC8784595
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Abstract

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus that invades the host central nervous system (CNS) and causes neurological dysfunction. Microglia are key immune cells in the CNS, however, whether and how they response to PHEV infection remains unclear. Herein, microglial activation and proliferation were detected in the CNS of PHEV-infected mice, as along with the proinflammatory response. Moreover, the production of proinflammatory cytokines induced by moderately activated microglia limited viral replication in the early stage of infection. Microglial depletion assays showed that during late infection, excess activation of microglia aggravated neurological symptoms, BBB destruction, and peripheral monocyte/macrophage infiltration into the CNS. Using an in vitro brain slice model, PHEV was identified to specifically and moderately induce microglial activation in the absence of peripheral immune cells infiltration. Consistently, macrophage clearance from circulating blood indicated that peripheral monocytes/macrophages crossing the BBB of mice were responsible for excess activation of microglia and CNS damage in late PHEV infection. Overall, our findings provide evidence supporting a dual role for microglia in the host CNS in response to coronavirus PHEV invasion.

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  • After infection with porcine hemagglutinating encephalomyelitis virus, circulating monocytes/macrophages crossed the blood-brain barrier into the central nervous system in model mice, recruited by activated microglia.

    “After infection with the porcine hemagglutinating encephalomyelitis virus, Jing Zhang et al. observed that circulating monocytes/macrophages crossed the BBB into the central nervous system in model mice, recruited by activated microglia (27).”

    From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [27]

    The Results section reports that circulating monocytes/macrophages crossed the BBB into the CNS of PHEV-infected mice. The Discussion’s Figure 6 description attributes their initial recruitment to rapid viral replication and increased BBB permeability, not to activated microglia. It says excess microglial activation later promotes further macrophage infiltration by aggravating BBB damage. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Zhang, J., Li, Z., Lu, H., Shi, J., Gao, R., Ma, Y., Lan, Y., Guan, J., Zhao, K., Gao, F., & He, W.
Affiliations
Jilin University (CN)
Corresponding author
He, Wenqi
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2022-01-10
Volume
12
Pages
804625-804625
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2021.804625
PMC
PMC8784595
OpenAlex
W4205858626
Cited by
10
References
5
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2
FWCI
0.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (32172828, 31902262, 32172805)
  • Jilin Scientific and Technological Development Program (20210202041NC)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
porcine hemagglutinating encephalomyelitis virus, microglial activation, neurotropic coronavirus, central nervous system infection, inflammatory cytokines, blood-brain barrier disruption, monocyte/macrophage infiltration, microglial depletion, viral replication, neurological damage
MeSH terms
Betacoronavirus 1, Animals, Blood-Brain Barrier, Coronaviridae Infections, Macrophages, Male, Mice, Inbred BALB C, Monocytes, Microglia, Mice

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