Anthracyclines inhibit SARS-CoV-2 infection

Wang, Zhen; Pan, Qinghua; Ma, Ling; Zhao, Jin; McIntosh, Fiona; Liu, Zhenlong; Ding, Shilei; Lin, Rongtuan; Chen, Shan; Finzi, Andrés; Liang, Chen

doi:10.1016/j.virusres.2023.199164

Cited by 2 publications

(2 citation statements)

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“…Transfection was performed using polyethyleneimine (PEI; Sigma-Aldrich, St. Louis, MO, USA; cat. 913375), as previously described [31].…”

Section: Cell Culturementioning

confidence: 99%

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SARS-CoV-2 Accessory Protein ORF8 Targets the Dimeric IgA Receptor pIgR

Laprise,

Arduini,

Duguay

et al. 2024

Viruses

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SARS-CoV-2 is a highly pathogenic respiratory virus that successfully initiates and establishes its infection at the respiratory mucosa. However, little is known about how SARS-CoV-2 antagonizes the host’s mucosal immunity. Recent findings have shown a marked reduction in the expression of the polymeric Ig receptor (pIgR) in COVID-19 patients. This receptor maintains mucosal homeostasis by transporting the dimeric IgA (dIgA) and pentameric IgM (pIgM) across mucosal epithelial cells to neutralize the invading respiratory pathogens. By studying the interaction between pIgR and SARS-CoV-2 proteins, we discovered that the viral accessory protein Open Reading Frame 8 (ORF8) potently downregulates pIgR expression and that this downregulation activity of ORF8 correlates with its ability to interact with pIgR. Importantly, the ORF8-mediated downregulation of pIgR diminishes the binding of dIgA or pIgM, and the ORF8 proteins of the variants of concern of SARS-CoV-2 preserve the function of downregulating pIgR, indicating the importance of this conserved activity of ORF8 in SARS-CoV-2 pathogenesis. We further observed that the secreted ORF8 binds to cell surface pIgR, but that this interaction does not trigger the cellular internalization of ORF8, which requires the binding of dIgA to pIgR. These findings suggest the role of ORF8 in SARS-CoV-2 mucosal immune evasion.

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“…Transfection was performed using polyethyleneimine (PEI; Sigma-Aldrich, St. Louis, MO, USA; cat. 913375), as previously described [31].…”

Section: Cell Culturementioning

confidence: 99%

“…12260), and psPAX2 (lentivirus packaging plasmid; Addgene, cat. 12260) to generate lentiviral vectors carrying ORF8 encoded by the pLVX-E1alpha-IRES-Puro expression vector, as previously described [31]. To generate pIgR domain deletions, a set of 6 primers was designed to amplify the extracellular-domaindeleted pIgR sequences (Table S1).…”

Section: Plasmidsmentioning

confidence: 99%