Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Vopr Virusol ; 66(2): 91-102, 2021 May 15.
Artigo em Russo | MEDLINE | ID: mdl-33993679

RESUMO

The Lassa virus one of the main etiological agent of hemorrhagic fevers in the world: according to WHO estimates, it affects 100,000 to 300,000 people annually, which results in up to 10,000 deaths [1]. Although expansion of Lassa fever caused by this pathogen is mostly limited to the West African countries: Sierra Leone, Liberia, Guinea and Nigeria, imported cases have been historically documented in Europe, the United States of America (USA), Canada, Japan, and Israel [2]. In 2017, WHO included the Lassa virus in the list of priority pathogens in need of accelerated research, development of vaccines, therapeutic agents and diagnostic tools regarding infections they cause [3]. This review describes main technological platforms used for the development of vaccines for the prevention of Lassa fever.


Assuntos
Febre Lassa , África Ocidental , Europa (Continente) , Humanos , Febre Lassa/epidemiologia , Febre Lassa/prevenção & controle , Vírus Lassa/imunologia , Vacinas Virais
2.
Vopr Virusol ; 66(1): 7-16, 2021 03 07.
Artigo em Russo | MEDLINE | ID: mdl-33683061

RESUMO

Ebola virus disease (EVD) (former Ebola hemorrhagic fever) is one of the most dangerous infectious diseases affecting humans and primates. Since the identification of the first outbreak in 1976, there have been more than 25 outbreaks worldwide, the largest of which escalated into an epidemic in 2014-2016 and caused the death of more than 11,000 people. There are currently 2 independent outbreaks of this disease in the eastern and western parts of the Democratic Republic of the Congo (DRC) at the same time. Bats (Microchiroptera) are supposed to be the natural reservoir of EVD, but the infectious agent has not yet been isolated from them. Most animal viruses are unable to replicate in humans. They have to develop adaptive mutations (AM) to become infectious for humans. In this review based on the results of a number of studies, we hypothesize that the formation of AM occurs directly in the human and primate population and subsequently leads to the development of EVD outbreaks.


Assuntos
Quirópteros , Ebolavirus , Doença pelo Vírus Ebola , Animais , República Democrática do Congo/epidemiologia , Surtos de Doenças , Ebolavirus/genética , Doença pelo Vírus Ebola/epidemiologia , Mutação
3.
Acta Naturae ; 13(4): 53-63, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35127147

RESUMO

Ebola fever is an acute, highly contagious viral disease with a mortality rate that can reach 90%. There are currently no licensed therapeutic agents specific to Ebola in the world. Monoclonal antibodies (MAbs) with viral-neutralizing activity and high specificity to the Ebola virus glycoprotein (EBOV GP) are considered as highly effective potential antiviral drugs. Over the past decade, nanobodies (single-domain antibodies, non-canonical camelid antibodies) have found wide use in the diagnosis and treatment of various infectious and non-infectious diseases. In this study, a panel of nanobodies specifically binding to EBOV GP was obtained using recombinant human adenovirus 5, expressing GP (Ad5-GP) for alpaca (Vicugna pacos) immunization, for the first time. Based on specific activity assay results, affinity constants, and the virus-neutralizing activity against the recombinant vesicular stomatitis virus pseudotyped with EBOV GP (rVSV-GP), the most promising clone (aEv6) was selected. The aEv6 clone was then modified with the human IgG1 Fc fragment to improve its pharmacokinetic and immunologic properties. To assess the protective activity of the chimeric molecule aEv6-Fc, a lethal model of murine rVSV-GP infection was developed by using immunosuppression. The results obtained in lethal model mice have demonstrated the protective effect of aEv6-Fc. Thus, the nanobody and its modified derivative obtained in this study have shown potential protective value against Ebola virus.

4.
Infect Genet Evol ; 63: 144-150, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29852294

RESUMO

Highly pathogenic avian influenza viruses (HPAIV) A(H5N8) of group B (Gochang1-like) have emerged in the Tyva Republic of eastern Russia in May 2016. Since November 2016, HPAIV A(H5N8) has spread throughout the European part of Russia. Thirty-one outbreaks were reported in domestic, wild and zoo birds in 2017. The present study aimed to perform a comparative analysis of new HPAIV A(H5N8) strains. Phylogenetic analysis revealed four genetically distinct subgroups in HPAIV A(H5N8) from the 2016-2017 season. Russian strains consisted of three subgroups with differences between isolates from Tyva, Siberia (Chany Lake), and the European part of Russia. Strains from the European part of Russia showed the beginnings of divergent evolution. Slight differences of the Voronezh strains were suggested by sensitivity to antiviral compounds. Testing for host-specific mutations in sequenced strains revealed the absence of mutations associated with possible increased tropism/virulence in mammalian species, including humans. Only one residue of polymerase basic-1, 13P, is discussed, because the L13P mutation increased complementary RNA synthesis in mammalian cells. We concluded that the evolution of HPAIV A(H5N8) is continuous. Surveillance in Russia revealed new cases of HPAIV A(H5N8) and led to the elaboration of prevention strategies, which should be implemented.


Assuntos
Vírus da Influenza A Subtipo H5N8/genética , Vírus da Influenza A Subtipo H5N8/patogenicidade , Influenza Aviária/virologia , Animais , Antivirais/farmacologia , Aves , Cães , Farmacorresistência Viral , Evolução Molecular , Influenza Aviária/epidemiologia , Células Madin Darby de Rim Canino , Mutação , Federação Russa/epidemiologia
5.
Acta Naturae ; 6(2): 95-105, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25093116

RESUMO

Current targeting strategies for genetic vectors imply the creation of a specific vector for every targeted receptor, which is time-consuming and expensive. Therefore, the development of a universal vector system whose surface can specifically bind molecules to provide efficient targeting is of particular interest. In this study, we propose a new approach in creating targeted vectors based on the genome of human adenovirus serotype 5 carrying the modified gene of the capsid protein pIX (Ad5-EGFP-pIX-ER): recombinant pseudoadenoviral nanoparticles (RPANs). The surfaces of such RPANs are able to bind properly modified chimeric nanoantibodies that specifically recognize a particular target antigen (carcinoembryonic antigen (CEA)) with high affinity. The efficient binding of nanoantibodies (aCEA-RE) to the RPAN capsid surfaces has been demonstrated by ELISA. The ability of the constructed vector to deliver target genes has been confirmed by experiments with the tumor cell lines A549 and Lim1215 expressing CEA. It has been shown that Ad5-EGFP-pIX-ER carrying aCEA-RE on its surface penetrates into the tumor cell lines A549 and Lim1215 via the CAR-independent pathway three times more efficiently than unmodified RPAN and Ad5-EGFP-pIX-ER without nanoantibodies on the capsid surface. Thus, RPAN Ad5-EGFP-pIX-ER is a universal platform that may be useful for targeted gene delivery in specific cells due to "nanoantibody-modified RPAN" binding.

6.
Acta Naturae ; 6(1): 76-84, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24772330

RESUMO

Anthrax is a particularly dangerous infectious disease that affects humans and livestock. It is characterized by intoxication, serosanguineous skin lesions, development of lymph nodes and internal organs, and may manifest itsself in either a cutaneous or septic form. The pathogenic agent is Bacillus anthracis, a grampositive, endospore-forming, rod-shaped aerobic bacterium. Efficacious vaccines that can rapidly induce a long-term immune response are required to prevent anthrax infection in humans. In this study, we designed three recombinant human adenovirus serotype-5-based vectors containing various modifications of the fourth domain of the B. anthracis protective antigen (PA). Three PA modifications were constructed: a secretable form (Ad-sPA), a non-secretable form (Ad-cPA), and a form with the protective antigen fused to the Fc fragment of immunoglobulin G2a (Ad-PA-Fc). All these forms exhibited protective properties against Bacillus anthracis. The highest level of protection was induced by the Ad-PA-Fc recombinant adenovirus. Our findings indicate that the introduction of the Fc antibody fragment into the protective antigen significantly improves the protective properties of the Ad-PA-Fc adenovirus against B. anthracis.

7.
Acta Naturae ; 6(4): 27-39, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25558392

RESUMO

Replication-defective adenoviral vectors are effective molecular tools for both gene therapy and gene vaccination. Using such vectors one can deliver and express target genes in different epithelial, liver, hematopoietic and immune system cells of animal and human origin. The success of gene therapy and gene vaccination depends on the production intensity of the target protein encoded by the transgene. In this work, we studied influence of Toll-like receptors (TLR) agonists on transduction and expression efficacy of adenoviral vectors in animal and human antigen-presenting cells. We found that agonists of TLR2, 4, 5, 7, 8 and 9 significantly enhance a production of the target protein in cells transduced with adenoviral vector having the target gene insert. The enhancement was observed in dendritic cells and macrophages expressing cytoplasmic (GFP), membrane (HA) or secretory (SEAP) proteins encoded by the respective rAd-vectors. Experiments in mice showed that enhancement of the transgene expression can be achieved in the organism of animals using a pharmaceutical-grade TLR4-agonist. In contrast to other TLR-agonists, the agonist of TLR3 substantially suppressed the expression of transgene in cells transduced with adenoviral vectors having insert of GFP or SEAP target genes. We propose that the enhancement of transgene expression is linked to the activation of MyD88→ NF-kB, while the inhibition of transgene expression depends on TRIF→ IRF signaling pathways. Both of these pathways jointly exploited by TLR4-agonists lead to the enhancement of transgene expression due to the dominant role of the MyD88→ NF-kB signaling.

8.
Bull Exp Biol Med ; 156(1): 122-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24319708

RESUMO

We determined conditions for effective transduction of multipotent mesenchymal stromal cells from human adipose tissue with adenoviral constructs carrying the gene of human bone morphogenetic protein BMP-2. The peak of transgene transcription and BMP-2 protein secretion in the transduced cultures was observed on day 6 after infection. The maximum transcription of BMP-2 gene and genes of osteogenic markers (bone sialoprotein, osteopontin, and osteocalcin) was observed in the medium containing sodium ß-glycerophosphate and ascorbic acid. Addition of D 3 vitamin did not enhance the expression of BMP-2 gene in transduced cells. The obtained cell cultures with high osteogenic potential can be used in bone tissue engineering.


Assuntos
Adenoviridae/genética , Proteína Morfogenética Óssea 2/genética , Células-Tronco Mesenquimais/metabolismo , Tecido Adiposo Branco/citologia , Antígenos CD/metabolismo , Proteína Morfogenética Óssea 2/biossíntese , Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular , Células Cultivadas , Humanos , Sialoproteína de Ligação à Integrina/metabolismo , Células-Tronco Mesenquimais/fisiologia , Osteocalcina/metabolismo , Osteopontina/metabolismo , Transcrição Genética , Transdução Genética
9.
Bull Exp Biol Med ; 154(4): 558-61, 2013 Feb.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-23486603

RESUMO

Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by progressive death of cerebral and spinal motorneurons. Using behavioral tests we studied the efficiency of gene-cell therapy in SOD1 G93A transgenic mice receiving xenotransplantation of human umbilical cord blood mononuclear cells genetically modified with adenoviral vectors encoding vascular endothelial growth factor (VEGF) and reporter green fluorescent protein (EGFP) genes. The cells were transplanted to mice on week 27 of life (preclinical stage of the disease). Behavioral tests (open field, grip strength test) showed that transplantation of umbilical cord blood mononuclear cells expressing VEGF significantly improved the parameters of motor and explorative activity, grip strength, and animal survival. Thus, gene-cell therapy based on genetically modified mononuclear cells expressing VEGF can be efficient for the treatment of amyotrophic lateral sclerosis.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Esclerose Amiotrófica Lateral/terapia , Superóxido Dismutase/metabolismo , Animais , Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Genética/métodos , Humanos , Camundongos , Camundongos Transgênicos , Superóxido Dismutase/genética , Transplante Heterólogo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Acta Naturae ; 4(3): 82-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23150806

RESUMO

Non-thermal plasma (NTP) consists of a huge amount of biologically active particles, whereas its temperature is close to ambient. This combination allows one to use NTP as a perspective tool for solving different biomedical tasks, including antitumor therapy. The treatment of tumor cells with NTP caused dose-dependent effects, such as growth arrest and apoptosis. However, while the outcome of NTP treatment has been established, the molecular mechanisms of the interaction between NTP and eukaryotic cells have not been thoroughly studied thus far. In this work, the mechanisms and the type of death of human colon carcinoma HCT 116 cells upon application of non-thermal argon plasma were studied. The effect of NTP on the major stress-activated protein p53 was investigated. The results demonstrate that the viability of HCT116 cells upon plasma treatment is dependent on the functional p53 protein. NTP treatment caused an increase in the intracellular concentration of p53 and the induction of the p53-controlled regulon. The p53-dependent accumulation of active proapoptotic caspase-3 was shown in NTP-treated cells. The study was the first to demonstrate that treatment of human colon carcinoma cells with NTP results in p53-dependent apoptosis. The results obtained contribute to our understanding of the applicability of NTP in antitumor therapy.

11.
Bull Exp Biol Med ; 154(2): 241-4, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23330135

RESUMO

We studied the interactions between sulfated polysaccharides, fucoidans from sea brown algae Laminaria japonica, Laminaria cichorioides, and Fucus evanescens, with human Toll-like receptors (TLR) expressed on membranes of cultured human embryonic kidney cells (HEK293-null, HEK293-TLR2/CD14, HEK293-hTLR4/CD14-MD2, and HEK293-hTLR5). Fucoidans interacted with TLR-2 and TLR-4, but not with TLR-5, and were nontoxic for the cell cultures. L. japonica fucoidan (1 mg/ml), L. cichorioides fucoidan (100 µg/ml and 1 mg/ml), and F. evanescens fucoidan (10 µg/ml-1 mg/ml) activated transcription nuclear factor NF-Ï°B by binding specifically to TLR-2. L. japonica fucoidan (100 µg/ml and 1 mg/ml), L. cichorioides fucoidan (10 µg/ml-1 mg/ml), and F. evanescens fucoidan (1 µg/ml-1 mg/ml) activated NF-Ï°B via binding to TLR-4. These results indicated that fucoidans could induce in vivo defense from pathogenic microorganisms of various classes.


Assuntos
Feófitas/química , Polissacarídeos/metabolismo , Receptores Toll-Like/metabolismo , Células HEK293 , Humanos , NF-kappa B/metabolismo , Polissacarídeos/farmacologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor 5 Toll-Like/metabolismo
12.
Acta Naturae ; 3(3): 64-70, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22649695

RESUMO

The present study is devoted to the feasibility of expressing the single-domain mini-antibody (nanoantibody) selected from the library of sequences of the variable domains of special single-stranded antibodies derived from an immunized camel, a gene of which was introduced into eukaryotic cells within a recombinant adenoviral vector. A vector bearing the gene of a single-domain nanoantibody was obtained using the AdEasy Adenoviral Vector System (Stratagene). This method of delivering the nanoantibody gene facilitates efficient expression of this gene and functional activity of the nanoantibody. The results obtained can be used to produce passive immunizing tools against pathogens or new-generation immunobiological antitoxic medication.

13.
Acta Naturae ; 3(3): 100-6, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22649700

RESUMO

Recombinant human adenovirus serotype 5 (Ad5/35F-IL2) with modified fibres containing the C-terminal domain fiber-knob of human adenovirus serotype 35, carrying the gene of recombinant human IL-2, has been designed. As a result of the fiber modification, the adenovirus can efficiently deliver the genetic information to bone marrow leukocytes and the tumor blood cells KG-1A (human myeloblastic leukemia cells) and U937 (human histiocytic lymphoma cells), which are normally resistant to Ad5 infection. The flow cytometry data reveal that the modified Ad5/35F penetrates into a population of monocytes, granulocytes, and blast cells of human bone marrow. The expression of interleukin-2 in CAR-negative bone marrow leukocytes (3682.52 ± 134.21 pg/ml) and the cell lines KG-1A (748.3 ± 32.8 pg/ml) and U937 (421.5 ± 59.4 pg/ml) transduced with adenovirus Ad5/35F-IL2 is demonstrated. The fiber-modified adenovirus can be used as a vector for the efficient gene delivery of interleukin-2 to human normal and tumor hematopoietic cells.

14.
Biochemistry (Mosc) ; 75(9): 1098-114, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21077829

RESUMO

Toll-like receptors (TLR) are among key receptors of the innate mammalian immune system. Receptors of this family are able to recognize specific highly conserved molecular regions (patterns) in pathogen structures, thus initiating reactions of both innate and acquired immune response finally resulting in the elimination of the pathogen. In this case every individual TLR type is able to bind a broad spectrum of molecules of microbial origin characterized by different chemical properties and structures. Recent data demonstrate the existence of a multistep mechanism of the TLR recognition of the pathogen in which, in addition to receptors proper, the involvement of different adapter molecules is necessary. However, functions of separate adapter molecules as well as the principles of formation of a multicomponent system of ligand-specific recognition are still not quite understandable. We describe all identified as well as possible (candidate) adapter TLR molecules by giving their brief characteristics, and we also propose generalized possible variants of the TLR ligand-specific recognition with involvement of adapter molecules.


Assuntos
Ligantes , Receptores Toll-Like/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Antígenos CD36/metabolismo , Drosophila , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Antígeno 96 de Linfócito/metabolismo , Domínios e Motivos de Interação entre Proteínas , Transdução de Sinais , Receptores Toll-Like/análise , Receptores Toll-Like/química
15.
Bull Exp Biol Med ; 145(4): 460-3, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19110594

RESUMO

The effects of gram-positive bacterial strains (Lactobacillus acidophilus and Lactobacillus rhamnosus) and their subcellular components on the survival of hemopoietic clonogenic cells were evaluated by the formation of endogenous splenic colonies. The effects of these preparations on NO production were studied by the spin-trap paramagnetic resonance spectroscopy. Bacterial preparations from gram-positive bacteria stimulated survival of hemopoietic clonogenic cells, but did not induce NO production in contrast to E. coli LPS.


Assuntos
Bactérias Gram-Positivas/fisiologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/fisiologia , Lipopolissacarídeos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Bactérias Gram-Positivas/química , Bactérias Gram-Positivas/citologia , Células-Tronco Hematopoéticas/microbiologia , Lactobacillus acidophilus/química , Lactobacillus acidophilus/citologia , Lactobacillus acidophilus/fisiologia , Lactobacillus rhamnosus/química , Lactobacillus rhamnosus/citologia , Lactobacillus rhamnosus/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Frações Subcelulares/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...