A5043439939- HIV Research and Treatment
- Mosquito-borne diseases and control
- Rabies epidemiology and control
- Viral Infections and Vectors
- Virology and Viral Diseases
- Immunotherapy and Immune Responses
- HIV/AIDS drug development and treatment
- Hepatitis C virus research
- Toxoplasma gondii Research Studies
- Hepatitis B Virus Studies
- Vector-borne infectious diseases
- Poxvirus research and outbreaks
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Allergic Rhinitis and Sensitization
- bioluminescence and chemiluminescence research
- HIV/AIDS Research and Interventions
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- Cytomegalovirus and herpesvirus research
- Antimicrobial Peptides and Activities
- Inflammasome and immune disorders
- Genomics, phytochemicals, and oxidative stress
- Extracellular vesicles in disease
- RNA modifications and cancer
Engelhardt Institute of Molecular Biology
2015-2024
Karolinska Institutet
2005-2022
Ministry of Health of the Russian Federation
2014-2019
Gamalei Institute of Epidemiology and Microbiology
2019
Russian Academy of Sciences
2013-2018
Chumakov Institute of Poliomyelitis and Viral Encephalitides
2016-2017
Yandex (Russia)
2015-2016
D.I. Ivanovsky Institute of Virology Russian Academy of Medical Sciences
2008-2014
Swedish Institute
2005-2010
University of Oslo
2006
Implantation of reporter-labeled tumor cells in an immunocompetent host involves a risk their immune elimination. We have studied this effect mouse model breast cancer after the orthotopic implantation mammary gland adenocarcinoma 4T1 genetically labelled with luciferase (Luc). Mice were implanted and two derivative Luc-expressing clones 4T1luc2 4T1luc2D6 exhibiting equal vitro growth rates. In vivo, daughter clone exhibited nearly same, 4T1luc2D6, lower rate than parental cells. The...
HIV-1 infection induces chronic oxidative stress. The resultant neurotoxicity has been associated with Tat protein. Here, we for the first time describe induction of stress by another protein, reverse transcriptase (RT). Expression RT in human embryonic kidney cells generated potent production reactive oxygen species (ROS), detected fluorescence-based probes. Quantitative RT-PCR demonstrated that expression HEK293 induced a 10- to 15-fold increased transcription phase II detoxifying enzymes...
Infection with tick-borne encephalitis virus (TBEV) causes pathological changes in the central nervous system. However, possible redox alterations infected cells that can contribute to pathogenicity remain unknown.In current study we explored ability of TBEV nonstructural protein 1 (NS1) induce oxidative stress and activate antioxidant defense via nuclear factor (erythroid-derived-2)-like 2/antioxidant response element (Nrf2/ARE) pathway.HEK 293T were transfected plasmid encoding NS1...
HIV-induced immune suppression results in the high prevalence of HIV/AIDS-associated malignancies including Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. HIV-infected people are also at an increased risk “non-AIDS-defining” not directly linked to but associated with viral infections. Their incidence is increasing despite successful antiretroviral therapy. The mechanism behind this phenomenon remains unclear. Here, we obtained daughter clones murine mammary gland adenocarcinoma...
The members of the Flaviviridae family are becoming an emerging threat for public health, causing increasing number infections each year and requiring effective treatment. consequences these can be severe include liver inflammation with subsequent carcinogenesis, endothelial damage hemorrhage, neuroinflammation, and, in some cases, death. mechanisms pathogenesis being actively investigated, but there still many gaps their understanding. Extracellular vesicles may play important roles...
Hepatitis C core protein is an attractive target for HCV vaccine aimed to exterminate infected cells. However, although highly immunogenic in natural infection, appears have low immunogenicity experimental settings. We design prototype based on core, and devise immunization regimens that would lead potent anti-core immune responses which circumvent the limitations earlier observed.Plasmids encoding with no translation initiation signal (pCMVcore); Kozak sequence (pCMVcoreKozak); IRES...
The efficacy of DNA vaccines is highly dependent on the methods used for their delivery and choice sites/targets gene injection, pointing at necessity a strict control over process. Here, we have investigated effect injection site expression immunogenicity in BALB/c mice, using as model weak immunogen, encoding firefly luciferase (Luc) delivered by superficial or deep with subsequent electroporation (EP). Immunization was assessed monitoring vivo 2D- 3D-bioluminescence imaging (BLI)...
DNA vaccines require a considerable enhancement of immunogenicity. Here, we optimized prototype vaccine against drug-resistant HIV-1 based on weak Th2-immunogen, reverse transcriptase (RT). We designed expression-optimized genes encoding inactivated wild-type and RTs (RT-DNAs) introduced them into mice by intradermal injections followed electroporation. RT-DNAs were administered as single or double primes with without cyclic-di-GMP, prime boost RT-DNA mixed luciferase-encoding plasmid...
Optimization of DNA vaccine delivery improves the potency immune response and is crucial to clinical success. Here, we inquired how such optimization impacts magnitude response, its specificity type. BALB/c mice were DNA-immunized with two model immunogens, HIV-1 protease reverse transcriptase by intramuscular or intradermal injections electroporation. immunogens co-delivered encoding luciferase. Delivery expression monitored in vivo bioluminescence imaging (BLI). The endpoint responses...
Mutations in reverse transcriptase (RT) confer high levels of HIV resistance to drugs. However, while conferring drug resistance, they can lower viral replication capacity (fitness). The molecular mechanisms behind remain largely unknown. aim the study was characterize effect drug-resistance mutations on RT expression. Genes encoding AZT-resistant RTs with single or combined D67N, K70R, T215F, and K219Q, derived from drug-resistant HIV-1 strains were designed expressed a variety eukaryotic...
Our objective is to create gene immunogens targeted against drug-resistant HIV-1, focusing on HIV-1 enzymes as critical components in viral replication and drug resistance. Consensus-based vaccines are specifically fit for variable pathogens such have many advantages over genes their expression-optimized variants. With this mind, we designed the consensus integrase (IN) of clade A strain predominant territory former Soviet Union its inactivated derivative with without mutations conferring...
Rabies is an infectious disease among humans and animals that remains incurable, despite its longstanding research history. The only way to prevent the prompt treatment, including vaccination as obligatory component administration of antirabies immunoglobulin a supplement. Since first performed in 19th century, large number different rabies vaccines have been developed. Progress molecular biology biotechnology enabled development effective safe technologies vaccine production. Currently,...
Immunization with naked genes (DNA-immunization) is a perspective modern approach to prophylactic as well therapeutic vaccination against pathogens, cancer and allergy. A panel of DNA immunogens has been developed, some are already in the clinical trials. However, immunogenicity vaccines, specifically those applied humans, needs considerable improvement. There several approaches increase vaccine immunogenicity. One implies modifications encoded immunogen that change its processing...
Reverse transcriptase (RT) is a key enzyme in viral replication and susceptibility to ART crucial target of immunotherapy against drug-resistant HIV-1. RT induces oxidative stress which undermines the attempts make it immunogenic. We hypothesized that artificial secretion may reduce more Inactivated multidrug-resistant (RT1.14opt-in) was N-terminally fused signal providing NS1 protein TBEV (Ld) generating optimized inactivated Ld-carrying RT1.14oil. Promotion prohibited proteasomal...
Currently, many DNA vaccines against infectious diseases are in clinical trials; however, their efficacy needs to be improved. The potency of immunogen can optimized by targeting technologies. In the current study, increase NS1 encoded plasmid, proteasome was applied. variants with or without translocation sequence and ornithine decarboxylase as a signal proteasomal degradation were tested for expression, localization, protein turnover, protection properties. Deletion abrogated presentation...
The efficient cell-mediated immune response clears cells expressing deoxyribonucleic acid (DNA) immunogens, but there are no methods to monitor this in vivo. We hypothesized that immune-mediated clearance can be monitored vivo if DNA immunogens coexpressed with reporter(s). To test this, we designed genes encoding human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT) fused via its N- or C-terminus 30-amino acid-long Gly-Ala-repeat of Epstein-Barr nuclear antigen the N-terminus...
Hepatitis delta virus (HDV) is a viroid-like blood-borne human pathogen that accompanies hepatitis B infection in 5% patients. HDV has been studied for four decades; however, the knowledge on its life-cycle and pathogenesis still sparse. The studies are hampered by absence of commercially-available HDV-specific antibodies. Here, we describe set reproducible methods expression E. coli His-tagged small antigen (S-HDAg), purification, production polyclonal anti-S-HDAg antibodies rabbits. S-HDAg...