RESUMO
Human T-lymphotropic virus (HTLV), the first human retrovirus has been discovered which is known to cause the age-old assassinating disease HTLV-1 associated myelopathy. Cancer caused by this virus is adult T cell leukemia/lymphoma which targets 10-20 million throughout the world. The effect of this virus extends to the fact that it causes chronic disease to the spinal cord resulting in loss of sensation and further causes blood cancer. So, to overcome the complications, we designed a subunit vaccine by the assimilation of B-cell, cytotoxic T-lymphocyte , and helper T-lymphocyte epitopes. The epitopes were joined together along with adjuvant and linkers and a vaccine was fabricated which was further subjected to 3D modeling. The physiochemical properties, allergenicity, and antigenicity were evaluated. Molecular docking and dynamics were performed with the obtained 3D model against toll like receptor (TLR-3) immune receptor. Lastly, in silico cloning was performed to ensure the expression of the designed vaccine in pET28a(+) expression vector. The future prospects of the study entailed the in vitro and in vivo experimental analysis for evaluating the immune response of the designed vaccine construct.
Assuntos
Algoritmos , Biologia Computacional/métodos , Desenho Assistido por Computador , Desenho de Fármacos , Epitopos , Infecções por HTLV-I/prevenção & controle , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Proteínas Virais/imunologia , Vacinas Virais/farmacologia , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Imunogenicidade da Vacina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Terciária de Proteína , Relação Estrutura-Atividade , Receptor 3 Toll-Like/agonistas , Receptor 3 Toll-Like/química , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/farmacologia , Proteínas Virais/química , Proteínas Virais/genética , Vacinas Virais/química , Vacinas Virais/genética , Vacinas Virais/imunologiaRESUMO
In the eukaryotic transcriptome, the evolutionary conserved circular RNAs naturally occur from the family of noncoding RNAs. Circular RNAs possess a unique feature to interact with nucleic acids and ribonucleoproteins and are establishing themselves as an obligatory composition for the regulatory messages which are encoded by the genome. The back-splicing mechanism leads to the formation of circularized RNA, and because of this they become resistant to exonuclease-mediated degradation. The differential and aberrant expression of circular RNAs can be detected with the help of various profiling methods by using serum, plasma, and tissue samples. In this chapter, we have highlighted the role of circular RNAs as putative biomarker for the detection of various human diseases along with its profiling methods. Here we have discussed the differentially expressed circular RNAs in neurological disorders and infectious diseases along with cancer diseases. For instance, in case of pulmonary tuberculosis, hsa_circRNA_001937 was upregulated, while hsa_circRNA_102101 got downregulated; Hsa_circ_000178 was depicted to get upregulated in breast cancer which is associated with disease progression. Furthermore, it has been observed that circRNAs are abundantly present within the mammalian brain tissues. In epileptic condition, Circ-EFCAB2 was observed to get notably upregulated within patients. Taking the above conditions into consideration, circular RNAs have proven themselves as promising noninvasive biomarker for the detection of human diseases.
Assuntos
Biomarcadores/análise , RNA/análise , Diagnóstico Precoce , Feminino , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/genética , Humanos , MicroRNAs/metabolismo , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/genética , Neoplasias/diagnóstico , Neoplasias/genética , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/genética , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/genética , Gravidez , Prognóstico , RNA/metabolismo , RNA Circular , RNA Longo não Codificante/análise , RNA Longo não Codificante/metabolismo , RNA Neoplásico/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNA , Tuberculose/diagnóstico , Tuberculose/genéticaRESUMO
Tuberculosis is a menacing disease caused eminently to the people inhabiting the tropical and sub-tropical nations. A holistic approach is required to generate T and B memory cells to effectuate a long-term exemption from the pulmonary tuberculosis. In this study, immunoinformatic approaches were used to design a multi-epitope-based subunit vaccine for pulmonary tuberculosis which may improve human immune system. The various B-cell, TH cell and TC cell binding epitopes were predicted for selected 2 membrane and 12 secretory proteins of Mycobacterium tuberculosis. The final vaccine construct was assembled by merging the predicted epitope sequences and an adjuvant at the N-terminal of the construct. Furthermore, the physiochemical characterization was done to check the molecular weight, aliphatic index, theoretical PI, hydropathicity and thermostable nature of the designed vaccine. The construct was a potential antigen while wasn't allergenic in nature. Tertiary modeling was performed, by filtering them a refined model was chosen and was docked with TLR-4 (immune receptor). Molecular docking and dynamic simulation was performed and the microscopic interaction between the vaccine construct (ligand) and TLR-4 receptor complex was verified. In silico cloning was used to fortify the expression and translation efficiency of the vaccine within an expression vector.