ArticleThe Journal of general virology2021
MERS-CoV infection causes brain damage in human DPP4-transgenic mice through complement-mediated inflammation.
Article in The Journal of general virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 12 citations in OpenAlex.
- Receptor-induced activation of MERS-CoV spike revealed by time-course cryo-EM.PLoS pathogens · 2026Article
- The C5a-C5aR1 axis facilitates blood-brain barrier disruption induced by EV-A71 infection through neutrophil activation.PLoS pathogens · 2026Article
- Exploring coronavirus cell entry with functional viromics.Journal of virology · 2026Review
- Comparative genomics provides insights into chromosomal evolution and immunological adaptation in horseshoe bats.Nature ecology & evolution · 2025Article
- The activation of complement C5a-C5aR1 axis in astrocytes facilitates the neuropathogenesis due to EV-A71 infection by upregulating CXCL1.Journal of virology · 2025Article
- Review
- Virus-induced brain pathology and the neuroinflammation-inflammation continuum: the neurochemists view.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Emerging and reemerging infectious diseases: global trends and new strategies for their prevention and control.Signal transduction and targeted therapy · 2024Review
- C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps.The Journal of clinical investigation · 2023Article
- Human microglial models to study host-virus interactions.Experimental neurology · 2023Review
- Review
- Immune Functions of Astrocytes in Viral Neuroinfections.International journal of molecular sciences · 2023Review
- Olfactory impairment in psychiatric disorders: Does nasal inflammation impact disease psychophysiology?Translational psychiatry · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The highly pathogenic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a severe respiratory virus. Recent reports indicate additional central nervous system (CNS) involvement. In this study, human DPP4 transgenic mice were infected with MERS-CoV, and viral antigens were first detected in the midbrain-hindbrain 4 days post-infection, suggesting the virus may enter the brainstem via peripheral nerves. Neurons and astrocytes throughout the brain were infected, followed by damage of the blood brain barrier (BBB), as well as microglial activation and inflammatory cell infiltration, which may be caused by complement activation based on the observation of deposition of complement activation product C3 and high expression of C3a receptor (C3aR) and C5a receptor (C5aR1) in neurons and glial cells. It may be concluded that these effects were mediated by complement activation in the brain, because of their reduction resulted from the treatment with mouse C5aR1-specific mAb. Such mAb significantly reduced nucleoprotein expression, suppressed microglial activation and decreased activation of caspase-3 in neurons and p38 phosphorylation in the brain. Collectively, these results suggest that MERS-CoV infection of CNS triggers complement activation, leading to inflammation-mediated damage of brain tissue, and regulating of complement activation could be a promising intervention and adjunctive treatment for CNS injury by MERS-CoV and other coronaviruses.
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