Abstract
SARS-CoV-2, which emerged in Wuhan (China), has become a great worldwide problem in 2020 and has led to more than 1,000,000 deaths worldwide. Many laboratories are searching for ways to fight this pandemic. We studied the action of the cellular antiviral protein tetherin, which is encoded by the BST2 gene. We deleted the transmembrane domain-encoding part of the gene in the Vero cell line. The transmembrane domain is a target for virus-antagonizing proteins. We showed a decrease in SARS-CoV-2 in cells with deleted transmembrane BST2 domains compared to the initial Vero cell line. Similar results were obtained for SARS-CoV and avian influenza virus. This finding may help the development of antiviral therapies competitively targeting the transmembrane domain of tetherin with viral-antagonizing proteins.
Highlights
Bone marrow stromal cell antigen 2 (BST2), known as tetherin, plays an important role in cellular antiviral response during infection by enveloped viruses mainly by preventing virus release as have been shown on human immunodeficiency virus 1 (HIV1) and Ebola virus (Gupta et al, 2009; Vande Burgt et al, 2015)
Following the transfection of Vero cells with plasmid DNA encoding CRISPR/Cas9 effectors and the corresponding RNA guides, the partial homozygous deletion of BST2 gene was confirmed by Sanger sequencing in one of the clones obtained by single-cell dilution after lipofection and exhibited a loss of the 73– 294 nucleotide region
Tetherin plays a key role in the cellular antiviral response by binding to released enveloped viruses, preventing subsequent infections
Summary
Bone marrow stromal cell antigen 2 (BST2), known as tetherin, plays an important role in cellular antiviral response during infection by enveloped viruses mainly by preventing virus release as have been shown on human immunodeficiency virus 1 (HIV1) and Ebola virus (Gupta et al, 2009; Vande Burgt et al, 2015). Tetherin antagonists encoded by certain viruses, such as HIV-1 Vpu protein and Ebola glycoprotein, have been shown to enhance the release of HIV-1 and Ebola viruses in fibroblasts and T cells treated by interferon-α (IFN-α) (Neil et al, 2008). The impact of the tetherin protein domains on production of SARS-CoV and SARS-CoV-2 viruses remains unaddressed
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