{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:10:05Z","timestamp":1793315405143,"version":"4.5.0"},"reference-count":81,"publisher":"American Society for Microbiology","issue":"17","license":[{"start":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T00:00:00Z","timestamp":1283299200000},"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":[[2010,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Tick-borne encephalitis virus (TBEV) (family\n            <jats:italic>Flaviviridae<\/jats:italic>\n            , genus\n            <jats:italic>Flavivirus<\/jats:italic>\n            ) accounts for approximately 10,000 annual cases of severe encephalitis in Europe and Asia. Here, we investigated the induction of the antiviral type I interferons (IFNs) (alpha\/beta IFN [IFN-\u03b1\/\u03b2]) by TBEV. Using strains Neudo\u0308rfl, Hypr, and Absettarov, we demonstrate that levels of IFN-\u03b2 transcripts and viral RNA are strictly correlated. Moreover, IFN induction by TBEV was dependent on the transcription factor IFN regulatory factor 3 (IRF-3). However, even strain Hypr, which displayed the strongest IFN-inducing activity and the highest RNA levels, substantially delayed the activation of IRF-3. As a consequence, TBEV can keep the level of IFN transcripts below the threshold value that would permit the release of IFN by the cell. Only after 24 h of infection have cells accumulated sufficient IFN transcripts to produce detectable amounts of secreted IFNs. The delay in IFN induction appears not to be caused by a specific viral protein, since the individual expressions of TBEV C, E, NS2A, NS2B, NS3, NS4A, NS4B, NS5, and NS2B-NS3, as well as TBEV infection itself, had no apparent influence on specific IFN-\u03b2 induction. We noted, however, that viral double-stranded RNA (dsRNA), an important trigger of the IFN response, is immunodetectable only inside intracellular membrane compartments. Nonetheless, the dependency of IFN induction on IFN promoter stimulator 1 (IPS-1) as well as the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2\u03b1) suggest the cytoplasmic exposure of some viral dsRNA late in infection. Using ultrathin-section electron microscopy, we demonstrate that, similar to other flaviviruses, TBEV rearranges intracellular membranes. Virus particles and membrane-connected vesicles (which most likely represent sites of virus RNA synthesis) were observed inside the endoplasmic reticulum. Thus, apparently, TBEV rearranges internal cell membranes to provide a compartment for its dsRNA, which is largely inaccessible for detection by cytoplasmic pathogen receptors. This delays the onset of IFN induction sufficiently to give progeny particle production a head start of approximately 24 h.\n          <\/jats:p>","DOI":"10.1128\/jvi.00176-10","type":"journal-article","created":{"date-parts":[[2010,6,17]],"date-time":"2010-06-17T01:55:47Z","timestamp":1276739747000},"page":"8470-8483","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":193,"title":["Tick-Borne Encephalitis Virus Delays Interferon Induction and Hides Its Double-Stranded RNA in Intracellular Membrane Vesicles"],"prefix":"10.1128","volume":"84","author":[{"given":"Anna K.","family":"O\u0308verby","sequence":"first","affiliation":[{"name":"Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, D-79008 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vsevolod L.","family":"Popov","sequence":"additional","affiliation":[{"name":"Center for Biodefense and Emerging Infectious Diseases, the University of Texas Medical Branch, Galveston, Texas 77555-0609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Niedrig","sequence":"additional","affiliation":[{"name":"Robert Koch Institute, D-13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedemann","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, D-79008 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1389"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02188-08"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.20.12828-12839.2005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.18.9798-9806.2004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00936-07"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00316-07"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50426-4"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2004.01022.x"},{"key":"e_1_3_2_10_2","first-page":"482","volume":"260","year":"1999","unstructured":"Courageot, J., E. 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