@article{Kriplani_N-2021_64658,
title = {Secreted SARS-CoV-2 ORF8 modulates the cytokine expression profile of human macrophages},
author = {Kriplani, N. and Clohisey, S. and Fonseca, S. and Fletcher, S. and Lee, H. and Ashworth, J. and Kurian, D. and Lycett, S. and Tait-Burkard, C. and Baillie, J. and Woolhouse, M. and Carding, S. and Stewart, J. and Digard, P.},
month = {aug},
year = {2021},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still adapting to its new human host. Attention has focussed on the viral spike protein, but substantial variation has been seen in the ORF8 gene. Here, we show that SARS-CoV-2 ORF8 protein undergoes signal peptide-mediated processing through the endoplasmic reticulum and is secreted as a glycosylated, disulphide-linked dimer. The secreted protein from the prototype SARS-CoV-2 virus had no major effect on viability of a variety of cell types, or on IFN or NF-κB signalling. However, it modulated cytokine expression from primary CSF1-derived human macrophages, most notably by decreasing IL-6 and IL-8 secretion. Furthermore, a sequence polymorphism L84S that appeared early in the pandemic associated with the Clade S lineage of virus, showed a markedly different effect, of increasing IL-6 production. We conclude that ORF8 sequence polymorphisms can potentially affect SARS-CoV-2 virulence and should therefore be monitored in sequencing-based surveillance.},
journal = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory Press},
url = {https://doi.org/10.1101/2021.08.13.456266},
}
