{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:27:47Z","timestamp":1785414467319,"version":"3.56.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004897","name":"Pennsylvania Department of Health","doi-asserted-by":"publisher","award":["SAP#4100095599"],"award-info":[{"award-number":["SAP#4100095599"]}],"id":[{"id":"10.13039\/100004897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The compact genomic organization of hepatitis B virus (HBV) has long hindered\n                        the development of reporter viruses that do not compromise viral gene\n                        expression and replication. Leveraging the advantage of an RNA-sensing and\n                        ADAR-editing-dependent cellular reporter system termed\n                      <jats:underline>r<\/jats:underline>\n                      eprogrammable\n                      <jats:underline>a<\/jats:underline>\n                      denosine\n                      <jats:underline>d<\/jats:underline>\n                      eaminase\n                      <jats:underline>a<\/jats:underline>\n                      cting on\n                      <jats:underline>R<\/jats:underline>\n                      NA\n                      <jats:underline>s<\/jats:underline>\n                      ensors (RADARS), we\n                        developed an HBV-RADARS reporter. In this system, the expression of the\n                        reporter gene is activated\n                      <jats:italic toggle=\"yes\">in trans<\/jats:italic>\n                      by HBV RNA-guided,\n                        cellular adenosine deaminase acting on RNA 1 (ADAR1)-dependent reporter RNA\n                        editing. Using a luciferase reporter, we systematically scanned all ADAR1\n                        targetable sites present in HBV RNAs and selected an optimal sensor\n                        sequence. As anticipated, the activation of reporter mRNA translation is HBV\n                        RNA sequence-specific and quantitatively correlates with the abundance of\n                        HBV RNA and cellular ADAR1 deaminase activity. The optimized HBV-RADARS\n                        system can be used with versatile reporter proteins in multiple HBV cell\n                        culture settings, including HBV replicon plasmid-transfected cells, cell\n                        lines expressing HBV RNAs from integrated transgenes, and cells infected\n                        with HBV. Particularly, using an antibiotic resistance gene as the reporter\n                        for HBV-RADARS allows for the phenotypic selection of HBV-infected HepG2\n                        cells expressing human sodium taurocholate cotransporting polypeptide.\n                        Therefore, this HBV RNA-sensing reporter system is compatible with authentic\n                        HBV infection and can serve as a versatile platform for high-throughput\n                        screening of compounds that inhibit HBV infection and genome-wide genetic\n                        screens to identify cellular factors required for HBV infection of\n                        hepatocytes.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Traditional recombinant hepatitis B virus (HBV) reporter viruses are\n                            compromised in replication fitness and restricted to a single round of\n                            infection. HBV-RADARS, in principle, does not interfere with the viral\n                            life cycle as it acts through sensing the presence of HBV RNA and thus\n                            reports\n                        <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                        HBV infection as well as the\n                            replication of transfected HBV replicons. The HBV-RADARS system\n                            represents a significant advancement in HBV research tool development\n                            and offers a replication-competent and highly adaptable reporter\n                            platform in live cells for genome-wide genetic and chemical screens.\n                            Hence, it opens new avenues for dissecting HBV-hepatocyte interactions\n                            and holds promises for the identification of host-encoded antiviral\n                            targets, thereby advancing efforts toward a functional cure for chronic\n                            HBV infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00922-25","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T12:53:21Z","timestamp":1760100801000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["A hepatitis B virus RNA-sensing and RNA-editing-dependent reporter                    system"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7199-0441","authenticated-orcid":false,"given":"Liren","family":"Sun","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05evayb02","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Therapeutics, Baruch S. Blumberg Institute","place":["Doylestown, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Snedeker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05evayb02","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Therapeutics, Baruch S. Blumberg Institute","place":["Doylestown, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8303-3614","authenticated-orcid":true,"given":"Liudi","family":"Tang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05evayb02","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Therapeutics, Baruch S. Blumberg Institute","place":["Doylestown, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00760-9"},{"key":"e_1_3_3_3_2","unstructured":"Anonymous. 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