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1.
Mol Biol ; 55(4): 538-547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465926

RESUMO

Most vaccines work by inducing neutralizing antibodies that target the viral envelope. Enveloped RNA viruses have evolved mechanisms for surface glycoproteins to evade host immune responses, which exhibit substantial variability, even among different strains. Natural infection and vaccines using native forms of surface proteins may induce broadly neutralizing antibodies, yet with low and ineffective levels. Class I membrane-fusion proteins of enveloped RNA viruses, HIV-1, influenza A virus, SARS-CoV-2, yield a stable conformation (so-called "pre-fusion") in providing fusion between viral and host cell membranes. Modified viral surface proteins that are based on these features induce neutralizing antibodies with activity available against a broad spectrum of circulating strains and make it possible to overcome the difficulties associated with escape/variability of viral antigen.

2.
Mol Biol (Mosk) ; 55(4): 585-597, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34432776

RESUMO

Most vaccines work by inducing neutralizing antibodies that target the viral envelope. Enveloped RNA viruses have evolved mechanisms for surface glycoproteins to evade host immune responses, which exhibit substantial variability, even among different strains. Natural infection and vaccines using native forms of surface proteins may induce broadly neutralizing antibodies, yet with low and ineffective levels. Class I membrane-fusion proteins of enveloped RNA viruses, HIV-1, influenza A virus, SARS-CoV-2, yield a stable conformation (so-called "pre-fusion") in providing fusion between viral and host cell membranes. Modified viral surface proteins that are based on these features induce neutralizing antibodies with activity available against a broad spectrum of circulating strains and make it possible to overcome the difficulties associated with escape/variability of viral antigen.


Assuntos
COVID-19 , Vacinas , Anticorpos Neutralizantes , Humanos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
3.
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.

4.
Oncogene ; 27(33): 4521-31, 2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-18408766

RESUMO

Prokaryotes of the genus Mycoplasma are the smallest cellular organisms that persist as obligate extracellular parasites. Although mycoplasma infection is known to be associated with chromosomal instability and can promote malignant transformation, the mechanisms underlying these phenomena remain unknown. Since persistence of many cellular parasites requires suppression of apoptosis in host cells, we tested the effect of mycoplasma infection on the activity of the p53 and nuclear factor (NF)-kappaB pathways, major mechanisms controlling programmed cell death. To monitor the activity of p53 and NF-kappaB in mycoplasma-infected cells, we used a panel of reporter cell lines expressing the bacterial beta-galactosidase gene under the control of p53- or NF-kappaB-responsive promoters. Cells incubated with media conditioned with different species of mycoplasma showed constitutive activation of NF-kappaB and reduced activation of p53, common characteristics of the majority of human tumor cells, with M. arginini having the strongest effect among the species tested. Moreover, mycoplasma infection reduced the expression level and inducibility of an endogenous p53-responsive gene, p21(waf1), and inhibited apoptosis induced by genotoxic stress. Infection with M. arginini made rat and mouse embryo fibroblasts susceptible to transformation with oncogenic H-Ras, whereas mycoplasma-free cells underwent irreversible p53-dependent growth arrest. Mycoplasma infection was as effective as shRNA-mediated knockdown of p53 expression in making rodent fibroblasts permissive to Ras-induced transformation. These observations indicate that mycoplasma infection plays the role of a p53-suppressing oncogene that cooperates with Ras in cell transformation and suggest that the carcinogenic and mutagenic effects of mycoplasma might be due to inhibition of p53 tumor suppressor function by this common human parasite.


Assuntos
Transformação Celular Neoplásica/metabolismo , Embrião de Mamíferos/metabolismo , Fibroblastos/metabolismo , Infecções por Mycoplasma/metabolismo , Mycoplasma/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/genética , Linhagem Celular , Transformação Celular Neoplásica/genética , Instabilidade Cromossômica/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Dano ao DNA/genética , Embrião de Mamíferos/microbiologia , Fibroblastos/microbiologia , Humanos , Camundongos , Infecções por Mycoplasma/genética , NF-kappa B/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Ratos , Elementos de Resposta/genética , Proteína Supressora de Tumor p53/genética
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