Please use this identifier to cite or link to this item:
10.1155/2017/7407136
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 |
Authors: | Latanova, Anastasia Petkov, Stefan Kuzmenko, Yulia Kilpelaïnen, Athina Ivanov, Alexander Smirnova, Olga Krotova, Olga Korolev, Sergey Hinkula, Jorma Karpov, Vadim Isaguliants, Maria Starodubova, Elizaveta Rīga Stradiņš University |
Keywords: | 1.6 Biological sciences;1.1. Scientific article indexed in Web of Science and/or Scopus database;Immunology and Allergy;Immunology;SDG 3 - Good Health and Well-being |
Issue Date: | 22-Jun-2017 |
Citation: | Latanova , A , Petkov , S , Kuzmenko , Y , Kilpelaïnen , A , Ivanov , A , Smirnova , O , Krotova , O , Korolev , S , Hinkula , J , Karpov , V , Isaguliants , M & Starodubova , E 2017 , ' 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 ' , Journal of Immunology Research , vol. 2017 , 7407136 . https://doi.org/10.1155/2017/7407136 |
Abstract: | Reverse transcriptase (RT) is a key enzyme in viral replication and susceptibility to ART and a crucial target of immunotherapy against drug-resistant HIV-1. 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-γ/IL-2, RT1.14opt-in induced granzyme B, and RT1.14oil induced perforin production. Perforin secretion correlated with coproduction of IFN-γ and IL-2 (R=0,97). Both DNA immunogens induced strong anti-RT antibody response. Ldpeptide 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. |
Description: | Publisher Copyright: © 2017 Anastasia Latanova et al. |
DOI: | 10.1155/2017/7407136 |
ISSN: | 2314-8861 |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
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Fusion_to_Flaviviral_Leader_Peptide_Targets_HIV_1_Reverse_Transcriptase_for_Secretion.pdf | 8.68 MB | Adobe PDF | View/Open |
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