Ageing Cells Lose Their Molecular 'Lock' Against Coronaviruses

While common human coronaviruses like HCoV-229E usually cause mild cold symptoms, they can lead to severe disease in older populations. Scientists have now pinpointed a specific host factor that helps explain this age-related vulnerability. Through genome-wide CRISPR screening, the study identifies a protein named UHRF1 as a potent viral restriction factor.

UHRF1 operates by preventing the virus from entering the cell in the first place. It achieves this through epigenetic regulation—specifically promoter hypermethylation—which effectively switches off the gene for APN, the receptor the virus uses as a gateway. By downregulating APN, UHRF1 denies the virus a foothold.

Crucially, the research reveals that UHRF1 levels drop significantly as we age. Experiments using primary alveolar macrophages (immune cells in the lungs) from elderly donors showed lower UHRF1 expression and a corresponding increase in APN receptors compared to younger samples. This loss of epigenetic control renders older cells more susceptible to infection, highlighting UHRF1 as a key component of our innate defence that weakens over time.