Acidic pH of early endosomes governs SARS-CoV-2 transport in host cells.

ABSTRACT: Endocytosis is a prominent mechanism for SARS-CoV-2 entry into host cells. Upon internalization into early endosomes (EEs), the virus is transported to late endosomes (LEs), where acidic conditions facilitate spike protein processing and viral genome release. Dynein and kinesin motors drive EE transport along microtubules; dynein moves EEs to the perinuclear region, while kinesins direct them towards the plasma membrane, creating a tug-of-war over the direction of transport. Here, we identify that the luminal pH of EEs is a key factor regulating the outcome of this tug-of-war. Among the known endosomal pH regulators, only the sodium-proton exchanger NHE9 has so far been genetically linked to severe COVID-19 risk. NHE9 functions as a proton leak pathway specifically on endosomes. We show th

SUBMITTER: Fares P 

PROVIDER: S-EPMC11815683 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature