RT Journal Article
SR Electronic
T1 The D614G Mutation Enhances the Lysosomal Trafficking of SARS-CoV-2 Spike
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.08.417022
DO 10.1101/2020.12.08.417022
A1 Chenxu Guo
A1 Shang-Jui Tsai
A1 Yiwei Ai
A1 Maggie Li
A1 Andrew Pekosz
A1 Andrea Cox
A1 Nadia Atai
A1 Stephen J. Gould
YR 2020
UL http://biorxiv.org/content/early/2020/12/09/2020.12.08.417022.abstract
AB The spike D614G mutation increases SARS-CoV-2 infectivity, viral load, and transmission but the molecular mechanism underlying these effects remains unclear. We report here that spike is trafficked to lysosomes and that the D614G mutation enhances the lysosomal sorting of spike and the lysosomal accumulation of spike-positive punctae in SARS-CoV-2-infected cells. Spike trafficking to lysosomes is an endocytosis-independent, V-ATPase-dependent process, and spike-containing lysosomes drive lysosome clustering but display poor lysotracker labeling and reduced uptake of endocytosed materials. These results are consistent with a lysosomal pathway of coronavirus biogenesis and raise the possibility that a common mechanism may underly the D614G mutation’s effects on spike protein trafficking in infected cells and the accelerated entry of SARS-CoV-2 into uninfected cells.Competing Interest StatementS.J.G is a paid consultant for Capricor, holds equity in Capricor, and is co-inventor of intellectual property licensed by Capricor. S.J.T. is co-inventor of intellectual property licensed by Capricor. C.G. is co-inventor of intellectual property licensed by Capricor. N.A. is an employee of Capricor.