Neuroinvasion by human respiratory coronaviruses

Area of Science:

• Neuroscience
• Virology
• Pathology

Background:

• Human coronaviruses (HCoV) are known to cause respiratory illnesses.
• HCoV have demonstrated the ability to infect neural cell cultures.
• The neurotropism and neuroinvasion potential of HCoV remain areas for definitive experimental evidence.

Purpose of the Study:

• To provide experimental evidence for HCoV neurotropism and neuroinvasion.
• To investigate the potential association between HCoV and multiple sclerosis (MS).
• To characterize HCoV RNA in human brain autopsy samples.

Main Methods:

• Analysis of 90 human brain autopsy samples from donors with neurological diseases and controls.
• Utilized stringent reverse transcription-PCR with dual primer pairs for HCoV strains 229E and OC43.
• Employed Southern hybridization and sequencing of nucleocapsid protein (N) gene amplicons.
• Confirmed viral RNA presence in brain parenchyma using in situ hybridization.

Main Results:

• HCoV RNA detected in 44% (229E) and 23% (OC43) of all brain samples.
• A statistically significant higher prevalence of OC43 was observed in MS patients (35.9%) compared to controls (13.7%).
• Sequencing revealed unique mutations in OC43 strains from MS patients.
• In situ hybridization confirmed viral RNA presence within brain parenchyma, outside blood vessels.

Conclusions:

• The presence of HCoV RNA in human brain samples supports neuroinvasion by these respiratory viruses.
• Findings suggest a potential association between OC43 and multiple sclerosis.
• Further research is required to differentiate between opportunistic and disease-associated viral presence in the brain.