<br><div> <head profile="http://www.w3.org/1999/xhtml/vocab"> <!--[if IE]><![endif]--> <meta http-equiv="Content-Type" content="text/html; charset=utf-8"/> <link rel="dns-prefetch" href="//scholar.google.com"/> <link rel="dns-prefetch" href="//pnas-movie.glencoesoftware.com"/> <link rel="dns-prefetch" href="//www.google.com"/> <link rel="dns-prefetch" href="//www.google-analytics.com"/> <link rel="dns-prefetch" href="//stats.g.doubleclick.net"/> <meta name="viewport" content="initial-scale=1, maximum-scale=1, width=device-width, user-scalable=yes"/> <link rel="shortcut icon" href="https://www.pnas.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon"/> <link rel="canonical" href="https://www.pnas.org/content/early/2020/07/09/2006750117"/> <meta name="Generator" content="Drupal 7 (http://drupal.org)"/> <link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="http://www.pnas.org/content/early/2020/07/09/2006750117.full.pdf"/> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="http://www.pnas.org/content/early/2020/07/09/2006750117.full.txt"/> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="http://www.pnas.org/content/early/2020/07/09/2006750117.ppt"/> <meta name="type" content="article"/> <meta name="category" content="research-article"/> <meta name="HW.identifier" content="/pnas/early/2020/07/09/2006750117.atom"/> <meta name="HW.pisa" content="pnas;2006750117v1"/> <meta name="DC.Format" content="text/html"/> <meta name="DC.Language" content="en"/> <meta name="DC.Title" content="Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus"/> <meta name="DC.Identifier" content="10.1073/pnas.2006750117"/> <meta name="DC.Date" content="2020-07-10"/> <meta name="DC.Publisher" content="National Academy of Sciences"/> <meta name="DC.Rights" content="Copyright © 2020 the Author(s). Published by PNAS.. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND)."/> <meta name="DC.AccessRights" content="open-access"/> <meta name="DC.Description" content="Hepatitis delta virus (HDV) aggravates hepatitis B virus (HBV) infection of liver cells. Although the viruses are evolutionarily unrelated, HDV depends on HBV because it requires the HBV envelope protein for its transmission. HDV is only described in humans, which has triggered diverse hypotheses regarding its evolution and origins. Here we show that spiny rats ( Proechimys semispinosus ) carry a counterpart to HDV that surprisingly does not cause hepatitis and is not linked to HBV. The rodent deltavirus finding alone, but also taken together with the recent deltavirus findings in snakes and other vertebrates and invertebrates, suggests that a deltavirus precursor may have infected mammals before it acquired dependence on HBV as seen in humans. Hepatitis delta virus (HDV) is a human hepatitis-causing RNA virus, unrelated to any other taxonomic group of RNA viruses. Its occurrence as a satellite virus of hepatitis B virus (HBV) is a singular case in animal virology for which no consensus evolutionary explanation exists. Here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species Proechimys semispinosus . The rodent deltavirus is highly distinct, showing a common ancestor with a recently described deltavirus in snakes. Reverse genetics based on a tandem minus-strand complementary DNA genome copy under the control of a cytomegalovirus (CMV) promoter confirms autonomous genome replication in transfected cells, with initiation of replication from the upstream genome copy. In contrast to HDV, a large delta antigen is not expressed and the farnesylation motif critical for HBV interaction is absent from a genome region that might correspond to a hypothetical rodent large delta antigen. Correspondingly, there is no evidence for coinfection with an HBV-related hepadnavirus based on virus detection and serology in any deltavirus-positive animal. No other coinfecting viruses were detected by RNA sequencing studies of 120 wild-caught animals that could serve as a potential helper virus. The presence of virus in blood and pronounced detection in reproductively active males suggest horizontal transmission linked to competitive behavior. Our study establishes a nonhuman, mammalian deltavirus that occurs as a horizontally transmitted infection, is potentially cleared by immune response, is not focused in the liver, and possibly does not require helper virus coinfection."/> <meta name="DC.Contributor" content="Sofia Paraskevopoulou"/> <meta name="DC.Contributor" content="Fabian Pirzer"/> <meta name="DC.Contributor" content="Nora Goldmann"/> <meta name="DC.Contributor" content="Julian Schmid"/> <meta name="DC.Contributor" content="Victor Max Corman"/> <meta name="DC.Contributor" content="Lina Theresa Gottula"/> <meta name="DC.Contributor" content="Simon Schroeder"/> <meta name="DC.Contributor" content="Andrea Rasche"/> <meta name="DC.Contributor" content="Doreen Muth"/> <meta name="DC.Contributor" content="Jan Felix Drexler"/> <meta name="DC.Contributor" content="Alexander Christoph Heni"/> <meta name="DC.Contributor" content="Georg Joachim Eibner"/> <meta name="DC.Contributor" content="Rachel A. Page"/> <meta name="DC.Contributor" content="Terry C. Jones"/> <meta name="DC.Contributor" content="Marcel A. Müller"/> <meta name="DC.Contributor" content="Simone Sommer"/> <meta name="DC.Contributor" content="Dieter Glebe"/> <meta name="DC.Contributor" content="Christian Drosten"/> <meta name="article:published_time" content="2020-07-10"/> <meta name="article:section" content="Biological Sciences"/> <meta name="citation_title" content="Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus"/> <meta name="citation_abstract" lang="en" content="<p>Hepatitis delta virus (HDV) is a human hepatitis-causing RNA virus, unrelated to any other taxonomic group of RNA viruses. Its occurrence as a satellite virus of hepatitis B virus (HBV) is a singular case in animal virology for which no consensus evolutionary explanation exists. Here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species <i>Proechimys semispinosus</i>. The rodent deltavirus is highly distinct, showing a common ancestor with a recently described deltavirus in snakes. Reverse genetics based on a tandem minus-strand complementary DNA genome copy under the control of a cytomegalovirus (CMV) promoter confirms autonomous genome replication in transfected cells, with initiation of replication from the upstream genome copy. In contrast to HDV, a large delta antigen is not expressed and the farnesylation motif critical for HBV interaction is absent from a genome region that might correspond to a hypothetical rodent large delta antigen. Correspondingly, there is no evidence for coinfection with an HBV-related hepadnavirus based on virus detection and serology in any deltavirus-positive animal. No other coinfecting viruses were detected by RNA sequencing studies of 120 wild-caught animals that could serve as a potential helper virus. The presence of virus in blood and pronounced detection in reproductively active males suggest horizontal transmission linked to competitive behavior. Our study establishes a nonhuman, mammalian deltavirus that occurs as a horizontally transmitted infection, is potentially cleared by immune response, is not focused in the liver, and possibly does not require helper virus coinfection.</p>"/> <meta name="citation_abstract" lang="en" scheme="executive-summary" content="<h3>Significance</h3> <p>Hepatitis delta virus (HDV) aggravates hepatitis B virus (HBV) infection of liver cells. Although the viruses are evolutionarily unrelated, HDV depends on HBV because it requires the HBV envelope protein for its transmission. HDV is only described in humans, which has triggered diverse hypotheses regarding its evolution and origins. Here we show that spiny rats (<i>Proechimys semispinosus</i>) carry a counterpart to HDV that surprisingly does not cause hepatitis and is not linked to HBV. The rodent deltavirus finding alone, but also taken together with the recent deltavirus findings in snakes and other vertebrates and invertebrates, suggests that a deltavirus precursor may have infected mammals before it acquired dependence on HBV as seen in humans.</p>"/> <meta name="citation_journal_title" content="Proceedings of the National Academy of Sciences"/> <meta name="citation_publisher" content="National Academy of Sciences"/> <meta name="citation_publication_date" content="2020/07/10"/> <meta name="citation_mjid" content="pnas;2006750117v1"/> <meta name="citation_id" content="2006750117v1"/> <meta name="citation_public_url" content="https://www.pnas.org/content/early/2020/07/09/2006750117"/> <meta name="citation_abstract_html_url" content="https://www.pnas.org/content/early/2020/07/09/2006750117.abstract"/> <meta name="citation_full_html_url" content="https://www.pnas.org/content/early/2020/07/09/2006750117.full"/> <meta name="citation_pdf_url" content="https://www.pnas.org/content/pnas/early/2020/07/09/2006750117.full.pdf"/> <meta name="citation_issn" content="0027-8424"/> <meta name="citation_issn" content="1091-6490"/> <meta name="citation_journal_abbrev" content="PNAS"/> <meta name="citation_doi" content="10.1073/pnas.2006750117"/> <meta name="citation_num_pages" content="7"/> <meta name="citation_article_type" content="Research Article"/> <meta name="citation_section" content="Biological Sciences"/> <meta name="citation_access" content="all"/> <meta name="citation_author" content="Sofia Paraskevopoulou"/> <meta name="citation_author_institution" content="Charité-Universitätsmedizin Berlin"/> <meta name="citation_author_orcid" content="https://orcid.org/0000-0003-2608-2596"/> <meta name="citation_author" content="Fabian Pirzer"/> <meta name="citation_author_institution" content="Charité-Universitätsmedizin Berlin"/> <meta name="citation_author_orcid" content="https://orcid.org/0000-0001-8525-8593"/> <meta name="citation_author" content="Nora Goldmann"/> <meta name="citation_author_institution" content="Justus Liebig University Giessen"/> <meta name="citation_author_institution" content="National Reference Centre for Hepatitis B Viruses and Hepatitis D Viruses"/> <meta name="citation_author_institution" content="German Centre for Infection Research (DZIF)"/> <meta name="citation_author" content="Julian Schmid"/> <meta name="citation_author_institution" content="University of Ulm"/> <meta name="citation_author_institution" content="Smithsonian Tropical Research Institute"/> <meta name="citation_author_orcid" content="https://orcid.org/0000-0003-1775-6958"/> <meta name="citation_author" content="Victor Max Corman"/> <meta name="citation_author_institution" content="Charité-Universitätsmedizin Berlin"/> <meta name="citation_author_institution" content="German Centre for Infection Research (DZIF)"/> <meta name="citation_author_orcid" content="https://orcid.org/0000-0002-3605-0136"/> <meta name="citation_author" content="Lina Theresa Gottula"/> <meta name="citation_author_institution" content="Charité-Universitätsmedizin Berlin"/> <meta name="citation_author_orcid" content="https://orcid.org/0000-0001-5518-3957"/> <meta name="citation_author" content="Simon Schroeder"/> <meta name="citation_author_institution" content="Charité-Universitätsmedizin Berlin"/> <meta name="citation_author" content="Andrea Rasche"/> <meta name="citation_author_institution" content="Charité-Universitätsmedizin Berlin"/> <meta name="citation_author_institution" content="German Centre for Infection Research (DZIF)"/> <meta name="citation_author_orcid" content="https://orcid.org/0000-0001-6693-1180"/> <meta name="citation_author" content="Doreen Muth"/> <meta name="citation_author_institution" content="Charité-Universitätsmedizin Berlin"/> <meta name="citation_author_orcid" content="https://orcid.org/0000-0001-9992-5393"/> <meta name="citation_author" content="Jan Felix Drexler"/> <meta name="citation_author_institution" content="Charité-Universitätsmedizin Berlin"/> <meta name="citation_author_institution" content="German Centre for Infection Research (DZIF)"/> <meta name="citation_author_institution" content="Sechenov University"/> <meta name="citation_author" content="Alexander Christoph Heni"/> <meta name="citation_author_institution" content="University of Ulm"/> <meta name="citation_author_institution" content="Smithsonian Tropical Research Institute"/> <meta name="citation_author" content="Georg Joachim Eibner"/> <meta name="citation_author_institution" content="Charité-Universitätsmedizin Berlin"/> <meta name="citation_author_institution" content="University of Ulm"/> <meta name="citation_author_institution" content="Smithsonian Tropical Research Institute"/> <meta name="citation_author" content="Rachel A. 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Holmes;citation_title=The diversity, evolution and origins of vertebrate RNA viruses;citation_pages=9-16;citation_volume=31;citation_year=2018"/> <meta name="citation_fulltext_world_readable" content=""/> <meta name="twitter:title" content="Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus"/> <meta name="twitter:card" content="summary_large_image"/> <meta name="twitter:image" content="https://www.pnas.org/content/early/2020/07/09/2006750117/F1.large.jpg"/> <meta name="twitter:description" content="Hepatitis delta virus (HDV) aggravates hepatitis B virus (HBV) infection of liver cells. Although the viruses are evolutionarily unrelated, HDV depends on HBV because it requires the HBV envelope protein for its transmission. HDV is only described in humans, which has triggered diverse hypotheses regarding its evolution and origins. Here we show that spiny rats ( Proechimys semispinosus ) carry a counterpart to HDV that surprisingly does not cause hepatitis and is not linked to HBV. The rodent deltavirus finding alone, but also taken together with the recent deltavirus findings in snakes and other vertebrates and invertebrates, suggests that a deltavirus precursor may have infected mammals before it acquired dependence on HBV as seen in humans. Hepatitis delta virus (HDV) is a human hepatitis-causing RNA virus, unrelated to any other taxonomic group of RNA viruses. Its occurrence as a satellite virus of hepatitis B virus (HBV) is a singular case in animal virology for which no consensus evolutionary explanation exists. Here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species Proechimys semispinosus . The rodent deltavirus is highly distinct, showing a common ancestor with a recently described deltavirus in snakes. Reverse genetics based on a tandem minus-strand complementary DNA genome copy under the control of a cytomegalovirus (CMV) promoter confirms autonomous genome replication in transfected cells, with initiation of replication from the upstream genome copy. In contrast to HDV, a large delta antigen is not expressed and the farnesylation motif critical for HBV interaction is absent from a genome region that might correspond to a hypothetical rodent large delta antigen. Correspondingly, there is no evidence for coinfection with an HBV-related hepadnavirus based on virus detection and serology in any deltavirus-positive animal. No other coinfecting viruses were detected by RNA sequencing studies of 120 wild-caught animals that could serve as a potential helper virus. The presence of virus in blood and pronounced detection in reproductively active males suggest horizontal transmission linked to competitive behavior. Our study establishes a nonhuman, mammalian deltavirus that occurs as a horizontally transmitted infection, is potentially cleared by immune response, is not focused in the liver, and possibly does not require helper virus coinfection."/> <meta name="og-title" property="og:title" content="Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus"/> <meta name="og-url" property="og:url" content="https://www.pnas.org/content/early/2020/07/09/2006750117"/> <meta name="og-site-name" property="og:site_name" content="PNAS"/> <meta name="og-description" property="og:description" content="Hepatitis delta virus (HDV) aggravates hepatitis B virus (HBV) infection of liver cells. Although the viruses are evolutionarily unrelated, HDV depends on HBV because it requires the HBV envelope protein for its transmission. HDV is only described in humans, which has triggered diverse hypotheses regarding its evolution and origins. Here we show that spiny rats ( Proechimys semispinosus ) carry a counterpart to HDV that surprisingly does not cause hepatitis and is not linked to HBV. The rodent deltavirus finding alone, but also taken together with the recent deltavirus findings in snakes and other vertebrates and invertebrates, suggests that a deltavirus precursor may have infected mammals before it acquired dependence on HBV as seen in humans. Hepatitis delta virus (HDV) is a human hepatitis-causing RNA virus, unrelated to any other taxonomic group of RNA viruses. Its occurrence as a satellite virus of hepatitis B virus (HBV) is a singular case in animal virology for which no consensus evolutionary explanation exists. Here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species Proechimys semispinosus . The rodent deltavirus is highly distinct, showing a common ancestor with a recently described deltavirus in snakes. Reverse genetics based on a tandem minus-strand complementary DNA genome copy under the control of a cytomegalovirus (CMV) promoter confirms autonomous genome replication in transfected cells, with initiation of replication from the upstream genome copy. In contrast to HDV, a large delta antigen is not expressed and the farnesylation motif critical for HBV interaction is absent from a genome region that might correspond to a hypothetical rodent large delta antigen. Correspondingly, there is no evidence for coinfection with an HBV-related hepadnavirus based on virus detection and serology in any deltavirus-positive animal. No other coinfecting viruses were detected by RNA sequencing studies of 120 wild-caught animals that could serve as a potential helper virus. The presence of virus in blood and pronounced detection in reproductively active males suggest horizontal transmission linked to competitive behavior. Our study establishes a nonhuman, mammalian deltavirus that occurs as a horizontally transmitted infection, is potentially cleared by immune response, is not focused in the liver, and possibly does not require helper virus coinfection."/> <meta name="og-type" property="og:type" content="article"/> <meta name="og-image" property="og:image" content="https://www.pnas.org/content/early/2020/07/09/2006750117/F1.large.jpg"/> <meta name="format-detection" content="telephone=no"/> <title>Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus | PNAS</title> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/default/files/advagg_css/css__zUOsaJT2-txr78Pro2jqp5HkKYs7CY9FbkfBemQXYlw__kiQOVz2drquY4Y9F8gINaFiOXWD3R3YCpizYXeeITSI__Jsi9FELnOGd8Izl-cQZlaPD8YovR4Sb_o7kms4MEc0E.css" media="all"/> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/all/modules/highwire/highwire/highwire.style.highwire.css?qd9zm1" media="all"/> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/default/files/advagg_css/css__IBZ9mHpn46TRp2BimuZ9LV8gzg5ve38Vt8Ur3OYiiIE__NtZxs4y1UkEH1BmzA2899OuPWrL4Vyfw35jNwF7gpGQ__Jsi9FELnOGd8Izl-cQZlaPD8YovR4Sb_o7kms4MEc0E.css" media="all"/> <link type="text/css" rel="stylesheet" href="//cdn.jsdelivr.net/qtip2/2.2.1/jquery.qtip.min.css" media="all"/> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/default/files/advagg_css/css__z7clwGNWpepGD_MPy0B7ftZ9V-_V15mFoM6ihgTvXBQ__X6SoMpUVch0hUZhU5GhhA43N8gkW5jGOyL-zhqU413o__Jsi9FELnOGd8Izl-cQZlaPD8YovR4Sb_o7kms4MEc0E.css" media="all"/> <link type="text/css" rel="stylesheet" href="//pnas-movie.glencoesoftware.com/static/video-js.min.css" media="all"/> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/default/files/advagg_css/css__7CYEtfDxMu3CEBZ53TQrEfMpO7duR_XdIuTLye9W7Cc__CzzPXev2zJRWVry4kyDAKuuERTizWaGzrN8gCp2auaE__Jsi9FELnOGd8Izl-cQZlaPD8YovR4Sb_o7kms4MEc0E.css" media="all"/> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/default/files/advagg_css/css__-KDpb--Yo63AujBOXd6ccTCn4ZuriGocNzETRJ-Fo2Q__jXPoluCdY9OJ1bes_FwCXcdI2BYpoO-G9OnF0StiEQA__Jsi9FELnOGd8Izl-cQZlaPD8YovR4Sb_o7kms4MEc0E.css" media="all"/> <!--[if lt IE 9]><![endif]--> <!--[if lt IE 10]><![endif]--> </head> <body id="wp_automatic_ReadabilityBody"> <!-- Google Tag Manager --> <noscript><iframe src="http://www.googletagmanager.com/ns.html?id=GTM-NDVQMQ4" height="0" width="0" style="display:none;visibility:hidden"></iframe></noscript> <!-- End Google Tag Manager --> <div class="page" id="page"> <!-- /.section-header --> <section role="main" class="section section-content" id="section-content"> <div class="container-fluid zone-wrapper zone-content-wrapper"> <div class="zone zone-content row"> <div class="region region-content col-narrow-22 col-narrow-offset-1"> <div id="block-panels-mini-whats-new-in" class="block block-panels-mini"> <div class="content"> <div class="panel-display panel-1col clearfix" id="mini-panel-whats_new_in"> <div class="panel-panel panel-col"> <div> <div class="panel-pane pane-snippet pane-pnas-physical-sciences wni-dropdown"> <h3 class="pane-title"><span class="pane-title-text">Physical Sciences</span></h3> <div class="pane-content"> <div class="pnas-physical-sciences" id="pnas-physical-sciences"> <div class="snippet-content"> <h4>Featured Portals</h4> <h4>Articles by Topic</h4> </div> </div> </div> </div> <div class="panel-pane pane-snippet pane-pnas-social-sciences wni-dropdown"> <h3 class="pane-title"><span class="pane-title-text">Social Sciences</span></h3> <div class="pane-content"> <div class="pnas-social-sciences" id="pnas-social-sciences"> <div class="snippet-content"> <h4>Featured Portals</h4> <h4>Articles by Topic</h4> </div> </div> </div> </div> <div class="panel-pane pane-snippet pane-pnas-biological-sciences wni-dropdown"> <h3 class="pane-title"><span class="pane-title-text">Biological Sciences</span></h3> <div class="pane-content"> <div class="pnas-biological-sciences" id="pnas-biological-sciences"> <div class="snippet-content"> <h4>Featured Portals</h4> <h4>Articles by Topic</h4> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div><!-- /.zone-content --> </div><!-- /.zone-content-wrapper --> </section> <!-- /.section-content --> <!-- /.section-footer --> </div> <!-- /.page --> </body> </div>
