Severe acute respiratory syndrome coronavirus ORF7a inhibits bone marrow stromal antigen 2 virion tethering through a novel mechanism of glycosylation interference
JournalJournal of Virology
PublisherAmerican Society for Microbiology
MetadataShow full item record
AbstractSevere acute respiratory syndrome (SARS) emerged in November 2002 as a case of atypical pneumonia in China, and the causative agent of SARS was identified to be a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter, but it also inhibits the release of virions of the retrovirus human immunodeficiency virus type 1 (HIV-1) by tethering budding virions to the host cell membrane. Further work has shown that BST-2 restricts the release of many other viruses, including the human coronavirus 229E (hCoV-229E), and the genomes of many of these viruses encode BST-2 antagonists to overcome BST-2 restriction. Given the previous studies on BST-2, we aimed to determine if BST-2 has the ability to restrict SARS-CoV and if the SARS-CoV genome encodes any proteins that modulate BST-2's antiviral function. Through an in vitro screen, we identified four potential BST-2 modulators encoded by the SARS-CoV genome: the papain-like protease (PLPro), nonstructural protein 1 (nsp1), ORF6, and ORF7a. As the function of ORF7a in SARS-CoV replication was previously unknown, we focused our study on ORF7a. We found that BST-2 does restrict SARS-CoV, but the loss of ORF7a leads to a much greater restriction, confirming the role of ORF7a as an inhibitor of BST-2. We further characterized the mechanism of BST-2 inhibition by ORF7a and found that ORF7a localization changes when BST-2 is overexpressed and ORF7a binds directly to BST-2. Finally, we also show that SARSCoV ORF7a blocks the restriction activity of BST-2 by blocking the glycosylation of BST-2.
SponsorsNational Institute of Allergy and Infectious Diseases, NIAID: R01AI087452; National Institute of Allergy and Infectious Diseases, NIAID: RO1AI1095569
Bone Marrow Stromal Antigen 2
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84949652761&doi=10.1128%2fJVI.02274-15&partnerID=40&md5=8d733fa8a44c12c40ad0bf2aca7bcf1a; http://hdl.handle.net/10713/12408