SARS-CoV-2 spike triggers TLR7-dependent endolysosome dysfunction and senescence in human astrocytes.

ABSTRACT: SARS-CoV-2 infection is associated with long-lasting neuropsychiatric and cognitive symptoms, collectively referred to as neuro-PASC. Emerging studies indicates that accelerate brain aging and cellular senescence in COVID brain could lead to altered neuroimmune responses and neurodegenerative outcomes. However, little is known about how cellular senescence is development in neuro-PASC. Here, we examined the role of spike protein subunit S1, a persistent viral antigen, in driving the development of cellular senescence in primary human astrocytes. We have demonstrated that S1 enters endolysosomes and induces endolysosome dysfunction and cellular senescence. Moreover, the multibasic motif is critical for such S1-induced damaging effects. Importantly, we identified Toll-like receptor 7 (TLR7),

SUBMITTER: Hasler WA 

PROVIDER: S-EPMC12577261 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature