Extracellular vesicles carry SARS-CoV-2 spike protein and serve as decoys for neutralizing antibodies.
Zach TroyerNajwa AlhusainiCaroline O TablerThomas SweetKarina Inacio Ladislau de CarvalhoDaniela M SchlatzerLenore CariasChristopher L KingKenneth MatreyekJohn C TiltonPublished in: Journal of extracellular vesicles (2021)
In late 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. SARS-CoV-2 and the disease it causes, coronavirus disease 2019 (COVID-19), spread rapidly and became a global pandemic in early 2020. SARS-CoV-2 spike protein is responsible for viral entry and binds to angiotensin converting enzyme 2 (ACE2) on host cells, making it a major target of the immune system - particularly neutralizing antibodies (nAbs) that are induced by infection or vaccines. Extracellular vesicles (EVs) are small membraned particles constitutively released by cells, including virally-infected cells. EVs and viruses enclosed within lipid membranes share some characteristics: they are small, sub-micron particles and they overlap in cellular biogenesis and egress routes. Given their shared characteristics, we hypothesized that EVs released from spike-expressing cells could carry spike and serve as decoys for anti-spike nAbs, promoting viral infection. Here, using mass spectrometry and nanoscale flow cytometry (NFC) approaches, we demonstrate that SARS-CoV-2 spike protein can be incorporated into EVs. Furthermore, we show that spike-carrying EVs act as decoy targets for convalescent patient serum-derived nAbs, reducing their effectiveness in blocking viral entry. These findings have important implications for the pathogenesis of SARS-CoV-2 infection in vivo and highlight the complex interplay between viruses, extracellular vesicles, and the immune system that occurs during viral infections.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- coronavirus disease
- induced apoptosis
- cell cycle arrest
- angiotensin converting enzyme
- mass spectrometry
- angiotensin ii
- randomized controlled trial
- signaling pathway
- cell death
- endoplasmic reticulum stress
- cell proliferation
- small molecule
- liquid chromatography
- pi k akt
- simultaneous determination
- capillary electrophoresis