{"id":2648,"date":"2023-02-17T06:57:34","date_gmt":"2023-02-17T12:57:34","guid":{"rendered":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/?p=2648"},"modified":"2023-02-17T07:05:05","modified_gmt":"2023-02-17T13:05:05","slug":"fibroblast-expressed-lrrc15-is-a-receptor-for-sars-cov-2-spike-and-controls-antiviral-and-antifibrotic-transcriptional-programs","status":"publish","type":"post","link":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/2023\/02\/17\/fibroblast-expressed-lrrc15-is-a-receptor-for-sars-cov-2-spike-and-controls-antiviral-and-antifibrotic-transcriptional-programs\/","title":{"rendered":"Fibroblast-expressed LRRC15 is a receptor for SARS-CoV-2 spike and controls antiviral and antifibrotic transcriptional programs"},"content":{"rendered":"<div class=\"panel body-content\"><div class=\"panel__container\">\n<p>(<a href=\"https:\/\/journals.plos.org\/plosbiology\/article?id=10.1371\/journal.pbio.3001967\">PLoS Biology<\/a>) Although ACE2 is the primary receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, a systematic assessment of host factors that regulate binding to SARS-CoV-2 spike protein has not been described. Here, we use whole-genome CRISPR activation to identify host factors controlling cellular interactions with SARS-CoV-2. Our top hit was a\u00a0<em>TLR<\/em>-related cell surface receptor called\u00a0<em>leucine-rich repeat-containing protein 15<\/em>\u00a0(<em>LRRC15<\/em>).\u00a0<em>LRRC15<\/em>\u00a0expression was sufficient to promote SARS-CoV-2 spike binding where they form a cell surface complex.\u00a0<em>LRRC15<\/em>\u00a0mRNA is expressed in human collagen-producing lung myofibroblasts and LRRC15 protein is induced in severe Coronavirus Disease 2019 (COVID-19) infection where it can be found lining the airways. Mechanistically, LRRC15 does not itself support SARS-CoV-2 infection, but fibroblasts expressing LRRC15 can suppress both pseudotyped and authentic SARS-CoV-2 infection in\u00a0<em>trans<\/em>. Moreover, LRRC15 expression in fibroblasts suppresses collagen production and promotes expression of IFIT, OAS, and MX-family antiviral factors. Overall, LRRC15 is a novel SARS-CoV-2 spike-binding receptor that can help control viral load and regulate antiviral and antifibrotic transcriptional programs in the context of COVID-19 infection.<\/p>\n<!-- <a rel=\"nofollow\" href=\"\/secure-location.php\" title=\"EZm iNV\">EZm iNV<\/a> --><\/div><\/div>","protected":false},"excerpt":{"rendered":"<p>(PLoS Biology) Although ACE2 is the primary receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, a systematic assessment of host factors that regulate binding to SARS-CoV-2 spike protein has not been described. Here, we use whole-genome CRISPR activation to identify host factors controlling cellular interactions with SARS-CoV-2. Our top hit was a\u00a0TLR-related cell [&hellip;]<\/p>\n","protected":false},"author":11,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"@Sydney_Uni researchers found a protein in the lungs that sticks to the #Covid19 virus like velcro. Maybe explains why some get very sick, others don't?","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":false,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[11,16],"tags":[],"class_list":["post-2648","post","type-post","status-publish","format-standard","hentry","category-covid","category-published-research"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/posts\/2648","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/users\/11"}],"replies":[{"embeddable":true,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/comments?post=2648"}],"version-history":[{"count":1,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/posts\/2648\/revisions"}],"predecessor-version":[{"id":2649,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/posts\/2648\/revisions\/2649"}],"wp:attachment":[{"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/media?parent=2648"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/categories?post=2648"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.unmc.edu\/healthsecurity\/transmission\/wp-json\/wp\/v2\/tags?post=2648"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}