SARS-CoV-2 infection in hiPSC-derived neurons is cathepsin-dependent and causes differential accumulation of HIF1ɑ and phosphorylated tau.

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to infect areas of the human brain and a subset of neurons in vitro. We have previously demonstrated that the virus enters human induced pluripotent stem cell (hiPSC)-derived neurons via an endosomal-lysosomal pathway. Here, we show that neuronal infection with both SARS-CoV-2 Wuhan and Omicron XBB.1.5 variants is dependent on cathepsins and can be blocked by an inhibitor of cathepsin B. The result was reproducible in non-transgenic hiPSC-derived cortical organoids. We further show that SARS-CoV-2 can replicate in neuron cultures, but the infectivity of the newly produced virions declined at 24 h post-infection despite a further increase in released viral RNA at later time points. The number of infected

SUBMITTER: Kettunen P 

PROVIDER: S-EPMC12597281 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature