The D614G Mutation Enhances the Lysosomal Trafficking of SARS-CoV-2 Spike.

BioRxiv : the Preprint Server for Biology
Chenxu GuoStephen J Gould

Abstract

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.

Citations

Feb 14, 2021·Scientific Reports·Luan Felipo Botelho-SouzaDeusilene Souza Vieira
May 1, 2021·International Journal of Molecular Sciences·Gustavo José da Silva PereiraClaudia Bincoletto

Datasets Mentioned

BETA
GM130
MT509475.1
MT509464.1

Methods Mentioned

BETA
Fluorescence microscopy
Fluorescence
transgenic
transfection
blood draw

Related Concepts

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.