Investigating the Immunogenic Properties of a Mutagenized NS3/4A-Based HCV Genotype 3a DNA Vaccine.

IF 1.5 4区 医学 Q4 IMMUNOLOGY
Viral immunology Pub Date : 2025-01-01 Epub Date: 2025-01-09 DOI:10.1089/vim.2024.0063
Palatip Chutoam, Kanokporn Srisucharitpanit, Uraiwan Intamaso
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引用次数: 0

Abstract

Chronic hepatitis C virus (HCV) infection poses a major health risk worldwide, with patients susceptible to liver cirrhosis and hepatocellular carcinoma. This study focuses on the development of effective therapeutic strategies for HCV infection through the investigation of immunogenic properties of a DNA construct based on the NS3/4A gene of HCV genotype (g)3a. Gene expression of the mutagenized (mut) NS3/4A target genes was assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Additionally, bioinformatics tools were employed to evaluate the impact of the mut-NS3/4A-based DNA vaccine. Analysis revealed increased mut-NS3/4A mRNA levels and target protein abundance compared with the native sequence. Elevated mut-NS3/NS4A levels could result from increased RNA stability and proper protein folding. Physicochemical analyses of the protein demonstrated favorable attributes such as thermostability and solubility. Three-dimensional mut-NS3/4A protein modeling confirmed its high stability and agreement with known protein structures. Additionally, potential immunogenic regions of both T and B cell epitopes were discovered based on peptide binding to major histocompatibility complex molecules of Asian origin. Importantly, these epitopes exhibited nonallergenic and nontoxic characteristics. These findings highlight the potential of the NS3/4A-based DNA construct as a promising candidate for an HCVg3a vaccine tailored for the Asian population, providing valuable insights for future immunotherapeutic approaches.

基于ns3 /4的HCV基因型3a突变DNA疫苗的免疫原性研究
慢性丙型肝炎病毒(HCV)感染是世界范围内的主要健康风险,患者易患肝硬化和肝细胞癌。本研究的重点是通过研究HCV基因型(g)3a的NS3/4A基因DNA构建体的免疫原性,开发有效的HCV感染治疗策略。通过逆转录-定量聚合酶链反应(RT-qPCR)和Western blot检测诱变(mut) NS3/4A靶基因的基因表达情况。此外,采用生物信息学工具评估基于mut- ns3 /4的DNA疫苗的影响。分析显示,与天然序列相比,mut-NS3/4A mRNA水平和靶蛋白丰度均有所增加。mut-NS3/NS4A水平升高可能是由于RNA稳定性和适当的蛋白质折叠增加所致。理化分析表明,该蛋白具有热稳定性和溶解度等优良特性。mut-NS3/4A蛋白的三维建模证实了其高稳定性和与已知蛋白结构的一致性。此外,基于与亚洲来源的主要组织相容性复合体分子的肽结合,发现了T和B细胞表位的潜在免疫原性区域。重要的是,这些表位表现出非过敏性和无毒的特点。这些发现突出了基于ns3 /4的DNA结构作为针对亚洲人群定制的HCVg3a疫苗的有希望候选物的潜力,为未来的免疫治疗方法提供了有价值的见解。
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来源期刊
Viral immunology
Viral immunology 医学-病毒学
CiteScore
3.60
自引率
0.00%
发文量
84
审稿时长
6-12 weeks
期刊介绍: Viral Immunology delivers cutting-edge peer-reviewed research on rare, emerging, and under-studied viruses, with special focus on analyzing mutual relationships between external viruses and internal immunity. Original research, reviews, and commentaries on relevant viruses are presented in clinical, translational, and basic science articles for researchers in multiple disciplines. Viral Immunology coverage includes: Human and animal viral immunology Research and development of viral vaccines, including field trials Immunological characterization of viral components Virus-based immunological diseases, including autoimmune syndromes Pathogenic mechanisms Viral diagnostics Tumor and cancer immunology with virus as the primary factor Viral immunology methods.
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