{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:35:52Z","timestamp":1775018152601,"version":"3.50.1"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Previous animal model experiments have shown a correlation between interferon gamma (IFN-\u03b3) expression and both survival from infection with attenuated rabies virus (RABV) and reduction of neurological sequelae. Therefore, we hypothesized that rapid production of murine IFN-\u03b3 by the rabies virus itself would induce a more robust antiviral response than would occur naturally in mice. To test this hypothesis, we used reverse engineering to clone the mouse IFN-\u03b3 gene into a pathogenic rabies virus backbone, SPBN, to produce the recombinant rabies virus designated SPBN\u03b3. Morbidity and mortality were monitored in mice infected intranasally with SPBN\u03b3 or SPBN(\u2212) control virus to determine the degree of attenuation caused by the expression of IFN-\u03b3. Incorporation of IFN-\u03b3 into the rabies virus genome highly attenuated the virus. SPBN\u03b3 has a 50% lethal dose (LD\n            <jats:sub>50)<\/jats:sub>\n            more than 100-fold greater than SPBN(\u2212).\n            <jats:italic>In vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            mouse experiments show that SPBN\u03b3 infection enhances the production of type I interferons. Furthermore, knockout mice lacking the ability to signal through the type I interferon receptor (IFNAR\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) cannot control the SPBN\u03b3 infection and rapidly die. These data suggest that IFN-\u03b3 production has antiviral effects in rabies, largely due to the induction of type I interferons.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Survival from rabies is dependent upon the early control of virus replication and spread. Once the virus reaches the central nervous system (CNS), this becomes highly problematic. Studies of CNS immunity to RABV have shown that control of replication begins at the onset of T cell entry and IFN-\u03b3 production in the CNS prior to the appearance of virus-neutralizing antibodies. Moreover, antibody-deficient mice are able to control but not clear attenuated RABV from the CNS. We find here that IFN-\u03b3 triggers the early production of type I interferons with the expected antiviral effects. We also show that engineering a lethal rabies virus to express IFN-\u03b3 directly in the infected tissue reduces rabies virus replication and spread, limiting its pathogenicity in normal and immunocompromised mice. Therefore, vector delivery of IFN-\u03b3 to the brain may have the potential to treat individuals who would otherwise succumb to infection with rabies virus.\n          <\/jats:p>","DOI":"10.1128\/jvi.01572-14","type":"journal-article","created":{"date-parts":[[2014,10,16]],"date-time":"2014-10-16T03:31:00Z","timestamp":1413430260000},"page":"312-322","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Expression of Interferon Gamma by a Recombinant Rabies Virus Strongly Attenuates the Pathogenicity of the Virus via Induction of Type I Interferon"],"prefix":"10.1128","volume":"89","author":[{"given":"Darryll A.","family":"Barkhouse","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"},{"name":"Center for Neurovirology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha A.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"},{"name":"Center for Neurovirology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily K.","family":"Bongiorno","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"},{"name":"Center for Neurovirology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurore","family":"Lebrun","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"},{"name":"Center for Neurovirology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milosz","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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