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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
Joint Authors
Isaguliants, Maria G.
Smirnova, Olga A.
Ivanov, Alexander V.
Starodubova, Elizaveta S.
Latanova, Anastasia
Petkov, Stefan
Kuzmenko, Yulia
Kilpeläinen, Athina
Krotova, Olga
Korolev, Sergey
Hinkula, Jorma
Karpov, Vadim
Source
Journal of Immunology Research
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-06-22
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
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.
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.
American Psychological Association (APA)
Latanova, Anastasia& Petkov, Stefan& Kuzmenko, Yulia& Kilpeläinen, Athina& Ivanov, Alexander V.& Smirnova, Olga A.…[et al.]. 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, no. 2017, pp.1-16.
https://search.emarefa.net/detail/BIM-1182069
Modern Language Association (MLA)
Latanova, Anastasia…[et al.]. 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 No. 2017 (2017), pp.1-16.
https://search.emarefa.net/detail/BIM-1182069
American Medical Association (AMA)
Latanova, Anastasia& Petkov, Stefan& Kuzmenko, Yulia& Kilpeläinen, Athina& Ivanov, Alexander V.& Smirnova, Olga A.…[et al.]. 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. 2017. Vol. 2017, no. 2017, pp.1-16.
https://search.emarefa.net/detail/BIM-1182069
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1182069