Comparison and Functional Relevance of Extracellular Vesicles Containing the Viral SARS-CoV-2 Spike or Ebola Virus Glycoprotein
Background
Viruses and extracellular vesicles (EVs) share many features, including their physical and chemical structure, biogenesis pathway, and cell entry mechanisms. During viral infections, EVs incorporating viral proteins can be released from infected cells. These viral protein-containing vesicles can contribute to viral pathogenesis by dampening the immune response, enhancing susceptibility, or inducing apoptosis in recipient cells. Nehls et al. (2019) demonstrated that EVs containing the Ebola virus glycoprotein (EBOV GP) can act immunomodulatory and trap neutralizing antibodies. Similarly, we and others have shown that the SARS-CoV-2 glycoprotein spike (S) can also be incorporated into EVs.
Methods
In this study, we aim to investigate the release of SARS-CoV-2 S-containing EVs in comparison to EBOV GP-containing vesicles, as well as their potential release after SARS-CoV-2 mRNA vaccination.
Results
We started by examining the influence of EBOV GP or SARS-CoV-2 S expression on the overall released EV population using nanoparticle tracking analysis (NTA). Expression of EBOV GP increased the quantity and mean diameter of EVs released, while expression of SARS-CoV-2 S did not alter the EV profile. For EBOV, the amount of GP-EVs released varies between strains and correlates with their pathogenicity. We could observe no such difference with S proteins from different SARS-CoV-2 variants. Given recent suggestions that S-containing circulating exosomes are induced by SARS-CoV-2 mRNA vaccines, we investigated the release of S-EVs from vaccine-treated primary human cells. Following vaccine treatment, predominantly muscle cells expressed the S protein and released a low amount of S-containing EVs. In contrast, other primary human cells, such as immune cells, endothelial cells, and fibroblasts, did not significantly express the S protein.
Conclusion
In summary, this study provides insights into the differential release of viral protein-containing EVs, which could have important implications for viral pathogenesis and immune responses.
Keywords
Viral Protein-Containing Vesicles, SARS-CoV-2 Spike Protein, Ebola Virus Glycoprotein (EBOV GP), Viral Pathogenesis
Authors
Elena Hagelauer1 (Corresponding Author: elena.hagelauer[at]med.uni-tuebingen[dot]de), Sophia Kieferle1, Simon Dreher2, Sophie Stopper1, Dan Hu1, Cora Weigert2, Michael Schindler1