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Fusion to Flavivira...
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
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- Latanova, Anastasia (author)
- Russian Academic Science, Russia; Gamaleja Research Centre Epidemiol and Microbiol, Russia; Karolinska Institute, Sweden
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- Petkov, Stefan (author)
- Karolinska Institutet
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- Kuzmenko, Yulia (author)
- Russian Academic Science, Russia
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- Kilpelainen, Athina (author)
- Karolinska Institute, Sweden
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- Ivanov, Alexander (author)
- Russian Academic Science, Russia
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- Smirnova, Olga (author)
- Russian Academic Science, Russia
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- Krotova, Olga (author)
- Russian Academic Science, Russia; Gamaleja Research Centre Epidemiol and Microbiol, Russia
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- Korolev, Sergey (author)
- Lomonosov Moscow State University, Russia
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- Hinkula, Jorma (author)
- Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten
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- Karpov, Vadim (author)
- Russian Academic Science, Russia
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- Isaguliants, Maria (author)
- Karolinska Institutet
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- Starodubova, Elizaveta (author)
- Russian Academic Science, Russia; Karolinska Institute, Sweden; Russian Academic Science, Russia
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(creator_code:org_t)
- HINDAWI LTD, 2017
- 2017
- English.
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In: Journal of Immunology Research. - : HINDAWI LTD. - 2314-8861 .- 2314-7156.
- Related links:
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Abstract
Subject headings
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- 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-gamma/IL-2, RT1.14opt-in induced granzyme B, and RT1.14oil induced perforin production. Perforin secretion correlated with coproduction of IFN-gamma and IL-2 (R = 0,97). 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Latanova, Anasta ...
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Petkov, Stefan
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Kuzmenko, Yulia
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Kilpelainen, Ath ...
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Ivanov, Alexande ...
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Smirnova, Olga
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show more...
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Krotova, Olga
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Korolev, Sergey
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Hinkula, Jorma
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Karpov, Vadim
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Isaguliants, Mar ...
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Starodubova, Eli ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Other Clinical M ...
- Articles in the publication
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Journal of Immun ...
- By the university
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Linköping University
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Karolinska Institutet