A Viroporin from SARS-CoV-2 Reduces the Infectivity of Human Immunodeficiency Virus type 1 (HIV-1)

A Viroporin from SARS-CoV-2 Reduces the Infectivity of Human Immunodeficiency Virus type 1 (HIV-1) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Viroporin from SARS-CoV-2 Reduces the Infectivity of Human Immunodeficiency Virus type 1 (HIV-1) Wyatt Henke, Hope Waisner, Sachith Polpitiya Arachchige, Maria Kalamvoki, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1739046/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Viroporins are virally encoded ion channels that are involved in virus assembly and release. Human immunodeficiency virus type 1 (HIV-1) and influenza A virus encode for viroporins. The human coronavirus SARS-CoV-2 encodes for at least two viroporin proteins, a small 75 amino acid transmembrane protein known as the envelope (E) protein and a larger 370 amino acid protein known as Orf3a. Here, we compared the HIV-1 virus infectivity in the presence of four different β-coronavirus E proteins. Results: We observed that the SARS-CoV-2 and SARS-CoV E proteins reduced the release of infectious HIV-1 yields by approximately 100-fold while MERS-CoV or HCoV-OC43 E proteins restricted HIV-1 infectivity to a lesser extent. Mechanistically, we show that the E proteins reduced the levels of HIV-1 protein synthesis in cells and that that the E protein neither affected reverse transcription nor genome integration. However, SARS-CoV-2 E protein activated the ER-stress pathway associated with the phosphorylation of eIF-2α, which is known to attenuate protein synthesis in cells. Other ever-expressed proteins (HSV-1 gD, HIV-1 gp160 and EGFP) did not cause phosphorylation of eIF-2α. Finally, we show that unlike the Vpu protein of HIV-1 and the Spike protein of SARS-CoV-2, the four E proteins and the SARS-CoV-2 N protein did not significantly down-regulate bone marrow stromal cell antigen 2 (BST-2). Conclusions: The results of this study indicate that while viroporins from homologous viruses can enhance virus release, that we show a viroporin from a heterologous virus can suppress HIV-1 protein synthesis and virus release. Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1739046","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":112869157,"identity":"710c0afc-8caa-40fb-b614-b5f75bb53616","order_by":0,"name":"Wyatt Henke","email":"","orcid":"","institution":"University of Kansas Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wyatt","middleName":"","lastName":"Henke","suffix":""},{"id":112869158,"identity":"36b29344-60b1-4ba9-8020-58ac6c2096c3","order_by":1,"name":"Hope Waisner","email":"","orcid":"","institution":"University of Kansas Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hope","middleName":"","lastName":"Waisner","suffix":""},{"id":112869159,"identity":"de09a229-dbb6-48ef-896d-468bb9f5de43","order_by":2,"name":"Sachith Polpitiya Arachchige","email":"","orcid":"","institution":"University of Kansas Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sachith","middleName":"Polpitiya","lastName":"Arachchige","suffix":""},{"id":112869160,"identity":"2a80ff30-e1ce-4ace-8c84-f2dfb0b3786f","order_by":3,"name":"Maria Kalamvoki","email":"","orcid":"","institution":"University of Kansas Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Kalamvoki","suffix":""},{"id":112869161,"identity":"d06c637e-2af5-4c65-b981-a2feaf217167","order_by":4,"name":"Edward Stephens","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYLACxgYGBn4eBJsQYIYok+whWYvBGWK18POfP/i4cIdNnvGZM6YbfjDYyG44QECL5IxkZuOZZ9KKzc72mN3sYUgzJqjF4AYzmzRv2+HEbed5zG4zMBxOJKjF/vxh9t+8bf8TN/eDtfwnrMWAIZmNmbftQOIG3h6QlgOEtUjcSDaWntmWnDjjzLGymz0GycYzCWnh7z/48HNhm11if0/yths/Kuxk+whpAQFmZHcSB5gJKxkFo2AUjIIRDQAmRkVuo8z0PAAAAABJRU5ErkJggg==","orcid":"","institution":"University of Kansas Medical Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Edward","middleName":"","lastName":"Stephens","suffix":""}],"badges":[],"createdAt":"2022-06-08 16:59:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1739046/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1739046/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22603725,"identity":"acb59c72-9265-4b77-8880-444491e0a848","added_by":"auto","created_at":"2022-06-13 22:02:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3040678,"visible":true,"origin":"","legend":"","description":"","filename":"Eproteinpaperretrovirology6102022.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1739046/v1_covered.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Viroporin from SARS-CoV-2 Reduces the Infectivity of Human Immunodeficiency Virus type 1 (HIV-1)","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-1739046/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-1739046/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1739046/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Viroporins are virally encoded ion channels that are involved in virus assembly and release. Human immunodeficiency virus type 1 (HIV-1) and influenza A virus encode for viroporins. The human coronavirus SARS-CoV-2 encodes for at least two viroporin proteins, a small 75 amino acid transmembrane protein known as the envelope (E) protein and a larger 370 amino acid protein known as Orf3a. Here, we compared the HIV-1 virus infectivity in the presence of four different β-coronavirus E proteins. \u003c/p\u003e\u003cp\u003eResults: We observed that the SARS-CoV-2 and SARS-CoV E proteins reduced the release of infectious HIV-1 yields by approximately 100-fold while MERS-CoV or HCoV-OC43 E proteins restricted HIV-1 infectivity to a lesser extent. Mechanistically, we show that the E proteins reduced the levels of HIV-1 protein synthesis in cells and that that the E protein neither affected reverse transcription nor genome integration. However, SARS-CoV-2 E protein activated the ER-stress pathway associated with the phosphorylation of eIF-2α, which is known to attenuate protein synthesis in cells. Other ever-expressed proteins (HSV-1 gD, HIV-1 gp160 and EGFP) did not cause phosphorylation of eIF-2α. Finally, we show that unlike the Vpu protein of HIV-1 and the Spike protein of SARS-CoV-2, the four E proteins and the SARS-CoV-2 N protein did not significantly down-regulate bone marrow stromal cell antigen 2 (BST-2). \u003c/p\u003e\u003cp\u003eConclusions: The results of this study indicate that while viroporins from homologous viruses can enhance virus release, that we show a viroporin from a heterologous virus can suppress HIV-1 protein synthesis and virus release.\u003c/p\u003e","manuscriptTitle":"A Viroporin from SARS-CoV-2 Reduces the Infectivity of Human Immunodeficiency Virus type 1 (HIV-1)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-06-13 22:02:20","doi":"10.21203/rs.3.rs-1739046/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c1ecfe0f-2ca1-4c37-9022-c8476fb22075","owner":[],"postedDate":"June 13th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-01-06T12:14:23+00:00","versionOfRecord":[],"versionCreatedAt":"2022-06-13 22:02:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1739046","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1739046","identity":"rs-1739046","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}