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RT induces oxidative stress which undermines the attempts to make it immunogenic. We hypothesized that artificial secretion may reduce the stress and make RT more immunogenic. Inactivated multidrug-resistant RT (RT1.14opt-in) was N-terminally fused to the signal providing secretion of NS1 protein of TBEV (Ld) generating optimized inactivated Ld-carrying enzyme RT1.14oil. Promotion of secretion prohibited proteasomal degradation increasing the half-life and content of RT1.14oil in cells and cell culture medium, drastically reduced the residual polymerase activity, and downmodulated oxidative stress. BALB\/c mice were DNA-immunized with RT1.14opt-in or parental RT1.14oil by intradermal injections with electroporation. Fluorospot and ELISA tests revealed that RT1.14opt-in and RT1.14oil induced IFN-<jats:italic>\u03b3<\/jats:italic>\/IL-2, RT1.14opt-in induced granzyme B, and RT1.14oil induced perforin production. Perforin secretion correlated with coproduction of IFN-<jats:italic>\u03b3<\/jats:italic>and IL-2 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>R<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0,97<\/mml:mn><\/mml:math>). Both DNA immunogens induced strong anti-RT antibody response. Ld peptide was not immunogenic. Thus, Ld-driven secretion inferred little change to RT performance in DNA immunization. Positive outcome was the abrogation of polymerase activity increasing safety of RT-based DNA vaccines. Identification of the molecular determinants of low cellular immunogenicity of RT requires further studies.<\/jats:p>","DOI":"10.1155\/2017\/7407136","type":"journal-article","created":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T21:05:19Z","timestamp":1498165519000},"page":"1-16","source":"Crossref","is-referenced-by-count":8,"title":["Fusion to Flaviviral Leader Peptide Targets HIV-1 Reverse Transcriptase for Secretion and Reduces Its Enzymatic Activity and Ability to Induce Oxidative Stress but Has No Major Effects on Its Immunogenic Performance in DNA-Immunized Mice"],"prefix":"10.1155","volume":"2017","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2260-6551","authenticated-orcid":true,"given":"Anastasia","family":"Latanova","sequence":"first","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia"},{"name":"Gamaleja Research Center of Epidemiology and Microbiology, Moscow, Russia"},{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Petkov","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3327-4967","authenticated-orcid":true,"given":"Yulia","family":"Kuzmenko","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4303-2443","authenticated-orcid":true,"given":"Athina","family":"Kilpel\u00e4inen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5659-9679","authenticated-orcid":true,"given":"Alexander","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4980-9754","authenticated-orcid":true,"given":"Olga","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6365-0372","authenticated-orcid":true,"given":"Olga","family":"Krotova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia"},{"name":"Gamaleja Research Center of Epidemiology and Microbiology, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2278-4451","authenticated-orcid":true,"given":"Sergey","family":"Korolev","sequence":"additional","affiliation":[{"name":"Chemistry Department, Belozersky Research Institute of Physico-Chemical Biology of Lomonosov Moscow State University, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorma","family":"Hinkula","sequence":"additional","affiliation":[{"name":"Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6685-1172","authenticated-orcid":true,"given":"Vadim","family":"Karpov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-2254","authenticated-orcid":true,"given":"Maria","family":"Isaguliants","sequence":"additional","affiliation":[{"name":"Gamaleja Research Center of Epidemiology and Microbiology, Moscow, Russia"},{"name":"Riga Stradins University, Riga, Latvia"},{"name":"M.P. 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