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

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a severe respiratory pathogen.
• Emerging evidence suggests MERS-CoV can affect the central nervous system (CNS).

Purpose of the Study:

• To investigate MERS-CoV entry into the CNS and its pathological effects.
• To explore the role of complement activation in MERS-CoV-induced neuroinflammation and damage.

Main Methods:

• Infection of human DPP4 transgenic mice with MERS-CoV.
• Detection of viral antigens and assessment of neuropathology, blood-brain barrier integrity, and immune cell activation.
• Treatment with a C5a receptor 1 (C5aR1)-specific monoclonal antibody (mAb) to evaluate complement's role.

Main Results:

• MERS-CoV viral antigens were detected in the brainstem, suggesting entry via peripheral nerves.
• Infection led to neuronal and astrocyte infection, blood-brain barrier damage, microglial activation, and inflammatory infiltration.
• Complement activation products (C3, C3aR, C5aR1) were observed in infected brain cells.
• Treatment with anti-C5aR1 mAb reduced viral load, suppressed microglial activation, and decreased neuronal apoptosis and p38 phosphorylation.

Conclusions:

• MERS-CoV infection of the CNS triggers complement activation, leading to inflammation-mediated brain tissue damage.
• Complement activation plays a key role in the neuropathology of MERS-CoV infection.
• Targeting complement activation represents a potential therapeutic strategy for MERS-CoV CNS injury.