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J Gen Virol . MERS-CoV infection causes brain damage in human DPP4-transgenic mice through complement-mediated inflammation

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  • J Gen Virol . MERS-CoV infection causes brain damage in human DPP4-transgenic mice through complement-mediated inflammation


    J Gen Virol


    . 2021 Oct;102(10).
    doi: 10.1099/jgv.0.001667.
    MERS-CoV infection causes brain damage in human DPP4-transgenic mice through complement-mediated inflammation


    Yuting Jiang 1 , Yuehong Chen 1 , Hong Sun 2 , Xiaolu Zhang 1 , Lei He 1 , Jiangfan Li 1 , Guangyu Zhao 1 , Shihui Sun 1



    Affiliations

    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.

    Keywords: MERS-CoV; complement system; neurologic injury; transgenic mice.

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