Sökning: onr:"swepub:oai:DiVA.org:liu-139656" >
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
-
- Latanova, Anastasia (författare)
- Russian Academic Science, Russia; Gamaleja Research Centre Epidemiol and Microbiol, Russia; Karolinska Institute, Sweden
-
- Petkov, Stefan (författare)
- Karolinska Institutet
-
- Kuzmenko, Yulia (författare)
- Russian Academic Science, Russia
-
visa fler...
-
- Kilpelainen, Athina (författare)
- Karolinska Institute, Sweden
-
- Ivanov, Alexander (författare)
- Russian Academic Science, Russia
-
- Smirnova, Olga (författare)
- Russian Academic Science, Russia
-
- Krotova, Olga (författare)
- Russian Academic Science, Russia; Gamaleja Research Centre Epidemiol and Microbiol, Russia
-
- Korolev, Sergey (författare)
- Lomonosov Moscow State University, Russia
-
- Hinkula, Jorma (författare)
- Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten
-
- Karpov, Vadim (författare)
- Russian Academic Science, Russia
-
- Isaguliants, Maria (författare)
- Karolinska Institutet
-
- Starodubova, Elizaveta (författare)
- Russian Academic Science, Russia; Karolinska Institute, Sweden; Russian Academic Science, Russia
-
visa färre...
-
(creator_code:org_t)
- HINDAWI LTD, 2017
- 2017
- Engelska.
-
Ingår i: Journal of Immunology Research. - : HINDAWI LTD. - 2314-8861 .- 2314-7156.
- Relaterad länk:
-
https://liu.diva-por... (primary) (Raw object)
-
visa fler...
-
http://downloads.hin...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Latanova, Anasta ...
-
Petkov, Stefan
-
Kuzmenko, Yulia
-
Kilpelainen, Ath ...
-
Ivanov, Alexande ...
-
Smirnova, Olga
-
visa fler...
-
Krotova, Olga
-
Korolev, Sergey
-
Hinkula, Jorma
-
Karpov, Vadim
-
Isaguliants, Mar ...
-
Starodubova, Eli ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Annan klinisk me ...
- Artiklar i publikationen
-
Journal of Immun ...
- Av lärosätet
-
Linköpings universitet
-
Karolinska Institutet