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Identification of novel monoclonal antibodies specific for the conserved epitopes in the E2 protein of genotype 2 classical swine fever virus: implication for differential diagnosis 基因2型猪瘟病毒E2蛋白保守表位特异性单克隆抗体的鉴定及其鉴别诊断意义
4区 医学 Q3 Medicine Pub Date : 2023-10-11 DOI: 10.3389/av.2023.12124
Jun Zhang, Zeming Guo, Yulin Zhao, Yida Yang, Pan Huang, Ning Wang, Zhuoyu Qian, Menghan He, Jianmin Wu, Lv Luo, Zhongsheng Li, Chungen Pan
Since the last century, the spread of the genotype 2 classical swine fever virus (CSFV) has caused significant issues for the pig breeding industries. Ideal strategies for controlling CSFV include vaccination and keeping farms free of CSFV. For vaccination, several attenuated CSFV viruses originating from genotype 1 are widely used; for the latter, accurate diagnosis is required for detection of the CSFV infection. Nucleic acid testing for CSFV usually uses tonsil samples, which requires an inconvenient sampling operation that injures pigs. Commercial serological tests for CSFV antibodies or antigens are unable to distinguish the genotype for originating virus. In this study, 20 mAbs were developed from the mice hybridoma cells. Four of the mAbs were identified to have the ability to only recognize the peptides derived from sub-genotype 2.1 strain, and two of them, MM1 and MM5, were further studied to identify critical binding sites (epitopes) on the E2 protein of CSFV. A total of 353 genotype 2 collections were made worldwide in GeneBank, 90.9% of which contained MM1 or MM5 epitopes. Moreover, 95.1% of sub-genotype 2.1 isolations contained MM5 epitope. Therefore, MM1 and MM5 have the potential to be developed as a diagnostic tool for detection of genotype 2 virus antigen by indirect ELISA or antibodies by competitive ELISA.
自上个世纪以来,基因型2经典猪瘟病毒(CSFV)的传播给养猪业造成了重大问题。控制猪瘟的理想策略包括接种疫苗和使农场远离猪瘟。在疫苗接种方面,广泛使用源自基因型1的几种CSFV减毒病毒;对于后者,需要准确诊断以发现CSFV感染。猪瘟病毒的核酸检测通常使用扁桃体样本,这需要一个不方便的采样操作,伤害猪。CSFV抗体或抗原的商业血清学检测无法区分原病毒的基因型。本研究从小鼠杂交瘤细胞中制备了20个单抗。其中4个单克隆抗体仅能识别来自2.1亚基因型菌株的肽,并对其中2个单克隆抗体MM1和MM5进行了进一步研究,以鉴定猪瘟病毒E2蛋白的关键结合位点(表位)。GeneBank共收集到353份2型基因,其中90.9%含有MM1或MM5表位。此外,95.1%的亚基因型2.1分离物含有MM5表位。因此,MM1和MM5具有发展潜力,可作为间接ELISA检测基因型2病毒抗原或竞争性ELISA检测抗体的诊断工具。
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引用次数: 0
Detection of SARS-CoV-2 using a laboratory-developed ultra-fast NextGenPCR test versus a conventional RT-PCR test 使用实验室开发的超快速NextGenPCR检测与传统RT-PCR检测SARS-CoV-2的比较
4区 医学 Q3 Medicine Pub Date : 2023-10-10 DOI: 10.3389/av.2023.11588
Katarína Čurová, Viera Lovayová, Mária Nagyová, Leonard Siegfried, Viliam Donič, Gert de Vos
The reverse transcription polymerase chain reaction (RT-PCR) is considered the gold standard method for the detection of viruses in a clinic. The aim of this study was to compare the ability of conventional RT-PCR test (FTD TM SARS-CoV-2 Test) and laboratory-developed ultra-fast PCR test (NextGenPCR TM SARS-CoV-2 RT-PCR Reagent Kit) to detect the coronavirus SARS-CoV-2 causing COVID-19. A total of 318 nasopharyngeal swab specimens were collected from people under investigation for COVID-19. Despite the collection of two swab specimens from each patient and their different processing, the analysis showed an overall agreement of 95.9% between the conventional and laboratory-developed tests. The positive percentage agreement was 90.5% (114/126) and the negative percentage agreement was 99.5% (191/192). The ultra-fast NextGenPCR method does not require the isolation of RNA, provides a result of 20–96 specimens within 57–82 min after sampling, and offers a simple procedure of sample processing, analysis, and evaluation. Our results indicate that this method can be considered a potential diagnostic method for the detection of SARS-CoV-2 virus in hospitals, healthcare facilities, and research laboratories.
逆转录聚合酶链反应(RT-PCR)被认为是临床检测病毒的金标准方法。本研究的目的是比较传统RT-PCR检测(FTD TM SARS-CoV-2 test)和实验室开发的超快速PCR检测(NextGenPCR TM SARS-CoV-2 RT-PCR试剂盒)检测引起COVID-19的冠状病毒SARS-CoV-2的能力。从接受COVID-19调查的人员中共收集了318份鼻咽拭子标本。尽管从每位患者身上采集了两个拭子标本,处理方法也不同,但分析显示,常规检测与实验室开发的检测之间的总体一致性为95.9%。阳性比例为90.5%(114/126),阴性比例为99.5%(191/192)。超快速NextGenPCR方法不需要分离RNA,在取样后57-82分钟内提供20-96个标本的结果,并提供简单的样品处理、分析和评估程序。我们的结果表明,该方法可以被认为是在医院、医疗机构和研究实验室检测SARS-CoV-2病毒的潜在诊断方法。
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引用次数: 0
The effects of SARS-CoV-2 on susceptible human cells SARS-CoV-2对易感人体细胞的影响
4区 医学 Q3 Medicine Pub Date : 2023-09-28 DOI: 10.3389/av.2023.11997
Zinaida Klestova
The biological consequences of viral infection result from biochemical, physiological, structural, morphological and genetic changes in infected cells. In productive infections, virus-induced biological changes in cells may be closely related to the efficiency of viral replication or to the recognition of these cells by the immune system. These changes are usually associated with cytocidal viruses, as in the case of the pandemic coronavirus SARS-CoV-2, which causes COVID-19. Many of these changes are required for effective viral replication. The physiological state of living cells has a significant impact on the outcome of viral infection, as the host cell provides the synthetic machinery, key regulatory molecules and precursors for newly synthesised viral proteins and nucleic acids. This review focuses on novel target cell types for SARS-CoV-2 exposure outside the respiratory tract. Findings and examples are collected that provide information on virus-cell interactions. The identification of unusual target cells for SARS-CoV-2 may help to explain the diverse symptoms in COVID-19 patients and the long-lasting effects after infection. In particular, the discovery of previously undescribed target cells for SARS-CoV-2 action needs to be considered to improve treatment of patients and prevention of infection.
病毒感染的生物学后果是由受感染细胞的生化、生理、结构、形态和遗传变化引起的。在生产性感染中,病毒诱导的细胞生物学变化可能与病毒复制的效率或免疫系统对这些细胞的识别密切相关。这些变化通常与杀细胞病毒有关,例如导致COVID-19的大流行冠状病毒SARS-CoV-2。许多这些变化是有效的病毒复制所必需的。活细胞的生理状态对病毒感染的结果有重要影响,因为宿主细胞为新合成的病毒蛋白和核酸提供了合成机制、关键调节分子和前体。本文综述了SARS-CoV-2在呼吸道外暴露的新靶细胞类型。收集了提供病毒-细胞相互作用信息的发现和例子。SARS-CoV-2异常靶细胞的鉴定可能有助于解释COVID-19患者的不同症状以及感染后的长期影响。特别是,需要考虑发现以前未描述的SARS-CoV-2作用的靶细胞,以改善患者的治疗和预防感染。
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引用次数: 0
Silent SARS-CoV-2 infection: seroprevalence study of SARS-CoV-2 anti- nucleocapsid IgG antibodies in Kragujevac, Serbia 无声SARS-CoV-2感染:塞尔维亚克拉古耶瓦茨地区SARS-CoV-2抗核衣壳IgG抗体血清流行率研究
4区 医学 Q3 Medicine Pub Date : 2023-09-26 DOI: 10.3389/av.2023.11996
Neda Cicaric, Vanja Canovic, Milica Stojkovic, Sanja Matic, Srdjan Stefanovic, Suzana Popovic, Danijela Todorovic, Natasa Djordjevic, Biljana Radenkovic, Marko Radenkovic, Vasilije Antic, Dejan Baskic
Serological testing is a powerful tool for analyzing the infectious disease burden landscape. Therefore, this study aimed to determine the seroprevalence against SARS-CoV-2 in the population of the municipality of Kragujevac, Serbia, with a particular reference to silent infections. A total of 4,804 participants over 19 years of age were randomly sampled for population-based seroprevalence research. Anti-N IgG antibodies were measured using rapid serological tests (UNscience ® ). The population was divided into four Cohorts, according to the history of SARS-CoV-2 infection and vaccination status with the whole inactivated virus vaccine BBIBP-CorV (Vero Cell ® , Sinopharm), as follows: Cohort I—confirmed SARS-CoV-2 infection, not vaccinated with the BBIBP-CorV vaccine; Cohort II—without confirmed SARS- CoV-2 infection, vaccinated with the BBIBP-CorV vaccine; Cohort III—confirmed SARS-CoV-2 infection, vaccinated with the BBIBP-CorV vaccine; Cohort IV—without confirmed SARS-CoV-2 infection, not vaccinated with the BBIBP-CorV vaccine (silent immunization). Cohorts I and IV included patients vaccinated with vaccines other than the BBIBP-CorV vaccine. The results showed that the overall prevalence of anti-N IgG antibodies was 56.5%, with the highest seroprevalence in Cohort III at 85.8%. In Cohort IV, the prevalence of anti-N IgG antibodies was 40.7%, attributed to silent immunization. The results also suggest that the prevalence of anti-N IgG antibodies decreased over time but remained detectable for more than 12 months in Cohort I. Since currently, there is no data on silent infection frequency in our country, these findings may provide insight into the extent of silent infections in the Serbian population.
血清学检测是分析传染病负担状况的有力工具。因此,本研究旨在确定塞尔维亚克拉古耶瓦茨市人口中SARS-CoV-2的血清流行率,特别是无声感染。共有4804名19岁以上的参与者被随机抽样进行基于人群的血清患病率研究。使用快速血清学测试(UNscience®)检测抗n IgG抗体。根据SARS-CoV-2感染史和接种全灭活疫苗BBIBP-CorV(中国医药集团Vero Cell®)的情况,将人群分为4个队列:队列1确诊为SARS-CoV-2感染,未接种BBIBP-CorV疫苗;队列ii -未确诊SARS- CoV-2感染,接种了BBIBP-CorV疫苗;iii队列确诊为SARS-CoV-2感染,接种了BBIBP-CorV疫苗;队列iv -未确诊SARS-CoV-2感染,未接种BBIBP-CorV疫苗(沉默免疫)。第1组和第4组包括接种了BBIBP-CorV疫苗以外疫苗的患者。结果显示,抗n IgG抗体的总体患病率为56.5%,其中队列III的血清阳性率最高,为85.8%。在队列IV中,抗n IgG抗体的患病率为40.7%,归因于沉默免疫。结果还表明,抗n IgG抗体的流行率随着时间的推移而下降,但在队列i中仍可检测到超过12个月。由于目前没有关于我国隐性感染频率的数据,这些发现可能有助于了解塞尔维亚人群中隐性感染的程度。
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引用次数: 0
Comprehensive codon usage analysis of the African Swine Fever Virus 非洲猪瘟病毒密码子使用的综合分析
4区 医学 Q3 Medicine Pub Date : 2023-09-18 DOI: 10.3389/av.2023.11562
Makoye Mhozya Kanyema, Mingyang Cheng, Jiawei Luo, Mei Lu, Xinyuan Xing, Yu Sun, Junhong Wang, Yiyuan Lu, Chunwei Shi, Yan Zeng, Guilian Yang, Xin Cao, Chunfeng Wang
The non-uniform usage of synonymous codons occurs in genomes of all organisms, including DNA and RNA viruses. The preferential selection of a codon at the expense of other synonymous codons within the same group is known as Codon Usage Bias. The understanding of this bias assists in unveiling the factors driving molecular evolution, as defined by the selection-mutation-drift theory. According to this model, molecular evolution is predominantly driven by mutation, natural selection, and genetic drift. Nevertheless, elements like nucleotide composition, gene length, and protein secondary structure also contribute to this process. Comprehensive genomic analyses that highlight the codon usage preference of the African Swine Fever Virus (ASFV) are infrequent. ASFV, a hemorrhagic and highly contagious viral disease, almost invariably results in 100% fatality among infected pigs and wild boars. This study, therefore, embarked on a thorough examination of codon usage patterns in ASFV’s complete genomic sequences, an endeavor of great relevance to molecular evolution studies, complex transmission models, and vaccine research. For an exhaustive evaluation of ASFV’s whole-genome codon usage, we used parameters like ENC, RSCU, and CAI. A Principal Component Analysis was carried out to reaffirm the interconnected RSCU lineages based on the continent, and their evolutionary relationships were later elucidated through phylogenetic tree construction. ASFV emerged as a low-biased codon user (ENC = 52.8) that is moderately adapted to its host. Its genome has a high AT composition (64.05%), suggesting the impact of mutational pressure on genomic evolution. However, neutrality plot analysis revealed natural selection’s slight supremacy over mutational pressure. The low codon bias (>45) implies ASFV’s diverse usage of synonymous codons within a given codon family, allowing for effective translation and subsequent successful viral replication cycles. Its moderate adaptation (CAI = 0.56) permits the virus to infect a range of hosts, including reservoirs such as warthogs and bush pigs. To the best of our knowledge, this is the pioneering report providing a comprehensive examination of ASFV’s complete genomic sequences. Consequently, research focusing on viral gene expression and regulation, gene function prediction, parasite-host interaction, immune dysfunction, and drug and vaccine design may find this report to be a valuable resource.
同义密码子的不均匀使用发生在所有生物体的基因组中,包括DNA和RNA病毒。密码子的优先选择以牺牲同一组内其他同义密码子为代价被称为密码子使用偏差。对这种偏见的理解有助于揭示驱动分子进化的因素,正如选择-突变-漂移理论所定义的那样。根据这个模型,分子进化主要是由突变、自然选择和遗传漂变驱动的。然而,核苷酸组成、基因长度和蛋白质二级结构等因素也有助于这一过程。强调非洲猪瘟病毒(ASFV)密码子使用偏好的全面基因组分析并不常见。非洲猪瘟是一种出血性和高度传染性的病毒性疾病,在受感染的猪和野猪中几乎总是导致100%的死亡率。因此,本研究开始了对非洲猪瘟全基因组序列密码子使用模式的深入研究,这一努力与分子进化研究、复杂传播模型和疫苗研究具有重要意义。为了全面评估ASFV的全基因组密码子使用情况,我们使用了ENC、RSCU和CAI等参数。通过主成分分析,确认了基于大陆的RSCU相互关联的谱系,并通过系统发育树的构建阐明了它们的进化关系。ASFV作为低偏密码子使用者出现(ENC = 52.8),对其宿主具有适度的适应性。其基因组具有较高的AT组成(64.05%),表明突变压力对基因组进化的影响。然而,中性图分析显示自然选择略高于突变压力。低密码子偏差(>45)意味着ASFV在给定密码子家族中对同义密码子的不同使用,允许有效的翻译和随后成功的病毒复制周期。它的中等适应性(CAI = 0.56)允许病毒感染一系列宿主,包括疣猪和丛林猪等宿主。据我们所知,这是一份开创性的报告,提供了非洲猪瘟完整基因组序列的全面检查。因此,关注病毒基因表达和调控、基因功能预测、寄生虫-宿主相互作用、免疫功能障碍以及药物和疫苗设计的研究可能会发现本报告是一个有价值的资源。
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引用次数: 0
Berberine inhibitory action against zika and dengue viruses in cell cultures 细胞培养中小檗碱对寨卡病毒和登革热病毒的抑制作用
IF 1.7 4区 医学 Q3 Medicine Pub Date : 2023-09-01 DOI: 10.3389/av.2023.11931
Denise A. Giannone, Luana E. Piccini, J. E. Brunetti, V. M. Quintana, E. Damonte, V. Castilla
Berberine (BBR) is a plant derived isoquinoline alkaloid that displays a great variety of biological activities. In this study we showed that BBR exhibits a strong antiviral activity with broad spectrum of inhibition against different strains of Zika virus (ZIKV) and the four serotypes of dengue virus (DENV) in Vero cells. The inhibitory effect of BBR on ZIKV and DENV-2 growth was also demonstrated in human cell lines. The analysis of BBR mode of action showed that the compound did not affect early events of viral multiplication cycle or viral protein expression. By contrast, BBR strongly impaired the formation of intracellular and extracellular infectious viral particles. Furthermore, BBR was able to inhibit ZIKV induced activation of ERK1/2 and p38 cell signaling pathways and also reduced p38 phosphorylation in uninfected cells. Like BBR, the p38 inhibitor SB202190 reduced p38 phosphorylation in both uninfected and ZIKV infected cultures and caused a significant diminishment of viral yields even when it was added late during the infection. These results suggest for the first time that the inhibitory effect of BBR on p38 signaling might contribute to the antiviral action of the compound against flaviviruses.
小檗碱(Berberine, BBR)是一种植物衍生的异喹啉生物碱,具有多种生物活性。本研究表明,BBR在Vero细胞中对寨卡病毒(ZIKV)的不同毒株和登革热病毒(DENV)的四种血清型具有较强的抗病毒活性,具有广谱抑制作用。在人细胞系中也证实了BBR对ZIKV和DENV-2生长的抑制作用。BBR作用模式分析表明,该化合物不影响病毒增殖周期的早期事件或病毒蛋白的表达。相比之下,BBR强烈地破坏了细胞内和细胞外感染性病毒颗粒的形成。此外,BBR能够抑制ZIKV诱导的ERK1/2和p38细胞信号通路的激活,并在未感染的细胞中降低p38磷酸化。与BBR一样,p38抑制剂SB202190在未感染和寨卡病毒感染的培养物中都降低了p38磷酸化,即使在感染后期添加,也会显著降低病毒产量。这些结果首次表明,BBR对p38信号的抑制作用可能有助于该化合物对黄病毒的抗病毒作用。
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引用次数: 0
In vitro induction of neutrophil extracellular traps by SARS-CoV-2 is biased by extracellular mitochondria 严重急性呼吸系统综合征冠状病毒2型体外诱导中性粒细胞细胞外陷阱受细胞外线粒体的影响
IF 1.7 4区 医学 Q3 Medicine Pub Date : 2023-09-01 DOI: 10.3389/av.2023.11801
J. Janko, M. Sláviková, Boris Klempa, Peter Celec, Michal Pastorek
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a highly variable course that is dependent on the host immune system reaction. Lung tissue damage, endothelial dysfunction, and microthrombosis in severe COVID-19 is linked to neutrophilia and the production of neutrophil extracellular traps (NETs). Previous studies have shown that NETs are involved in the pathology of COVID-19 and that the virus itself induces NET formation, although the underlying mechanisms are not clear. In this study, we aimed to investigate the induction of NETs by SARS-CoV-2 in vitro. We have found that both, infectious and heat-inactivated virus induce NETs formation. Surprisingly, cell culture media derived from uninfected Vero cells exhibit similar potency. This suggests that NET inducers other than the virus might be involved. Mitochondria released from dying cells during SARS-CoV-2 infection acting as damage-associated molecular patterns (DAMPs) were identified as potential contributors to neutrophil activation and NET formation. Our findings point to an important source of bias when analyzing NETs induction by SARS-CoV-2 in vitro, but also the immune reaction to viruses in general. Further implications for the understanding of COVID-19 pathogenesis remain to be elucidated.
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染有一个高度可变的过程,取决于宿主免疫系统的反应。严重新冠肺炎的肺组织损伤、内皮功能障碍和微血栓与中性粒细胞增多症和中性粒细胞外陷阱(NET)的产生有关。先前的研究表明,NET参与了新冠肺炎的病理学,并且病毒本身诱导了NET的形成,尽管其潜在机制尚不清楚。在本研究中,我们旨在研究严重急性呼吸系统综合征冠状病毒2型在体外对NETs的诱导作用。我们发现,传染性和热灭活病毒都能诱导NETs的形成。令人惊讶的是,来源于未感染的Vero细胞的细胞培养基显示出类似的效力。这表明可能与病毒以外的NET诱导物有关。严重急性呼吸系统综合征冠状病毒2型感染期间死亡细胞释放的线粒体作为损伤相关分子模式(DAMP)被确定为中性粒细胞激活和NET形成的潜在贡献者。我们的研究结果指出,在体外分析严重急性呼吸系统综合征冠状病毒2型对NETs的诱导,以及对病毒的免疫反应时,存在一个重要的偏差来源。对理解新冠肺炎发病机制的进一步影响仍有待阐明。
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引用次数: 0
Immunity towards human respiratory syncytial virus 对人类呼吸道合胞病毒的免疫
IF 1.7 4区 医学 Q3 Medicine Pub Date : 2023-08-24 DOI: 10.3389/av.2023.11887
Dahiana Correa, Diana M Giraldo, Salomon Gallego, N. Taborda, Juan C. Hernández
Respiratory infections remain a significant cause of morbidity and mortality, becoming a serious public health issue worldwide. The human respiratory syncytial virus (hRSV) is still one of the most relevant pathogenic agents involved in respiratory infections in children, the leading cause of bronchiolitis worldwide. In most cases, hRSV infection is not complicated; however, limited treatment and vaccine options increase the morbidity rates associated with bronchiolitis. The innate immune response governs the severity of the disease and controls the viral infection outcome. Current knowledge about the mechanisms involved in viral PAMPs (pathogen-associated molecular pattern molecules) recognition, genetic characteristics of the inflammatory response, and understanding of antiviral response is crucial for vaccine development and biomarker tools to predict complications and guide therapeutic management. Here, we review key concepts related to pathogenesis and immune response against hRSV, highlighting aspects that could be considered in vaccine development.
呼吸道感染仍然是发病率和死亡率的重要原因,已成为世界范围内一个严重的公共卫生问题。人类呼吸道合胞病毒(hRSV)仍然是儿童呼吸道感染中最相关的病原体之一,也是世界范围内毛细支气管炎的主要原因。在大多数情况下,hRSV感染并不复杂;然而,有限的治疗和疫苗选择增加了毛细支气管炎的发病率。先天免疫反应控制疾病的严重程度并控制病毒感染的结果。目前关于病毒PAMP(病原体相关分子模式分子)识别机制、炎症反应的遗传特征以及对抗病毒反应的理解的知识对于疫苗开发和生物标志物工具预测并发症和指导治疗管理至关重要。在这里,我们回顾了与hRSV的发病机制和免疫反应相关的关键概念,强调了在疫苗开发中可以考虑的方面。
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引用次数: 0
Initial high throughput proteomic analysis reveals alterations in CD19+ B lymphocyte profile in acute COVID-19 patients 初步高通量蛋白质组学分析揭示急性新冠肺炎患者CD19+B淋巴细胞谱的变化
IF 1.7 4区 医学 Q3 Medicine Pub Date : 2023-08-22 DOI: 10.3389/av.2023.11702
Miroslav Marcin, Ondrej Zahornacký, Mária Kacírová, M. Sulíková, Miloslava Bajer-Ďuráčová, P. Rehulka, P. Bober, J. Fedacko, P. Jarčuška, J. Sabó
The immune response to SARS-CoV-2, the virus responsible for COVID-19, involves intricate interactions between immune cells and viral antigens. CD19+ lymphocytes play a critical role in driving the humoral immune response. In this study, high-throughput proteomic analysis was performed using tandem mass spectrometry to investigate the changes in proteomic profiles of CD19+ whole cell lysates from 6 healthy individuals and 6 acute COVID-19 patients. The volcano plot and heat map showed significant differences in proteomic profiles between these two groups, indicating a distinct molecular signature associated with acute COVID-19. Enrichment analysis, especially over-representation analysis (ORA) using the Reactome database, revealed that proteins involved in neutrophil degranulation and interferon alpha/beta signaling pathways were among the most affected, indicating alterations in key defense processes. These findings, therefore, provide new insights into the molecular mechanisms underlying CD19+ cell responses in acute COVID-19.
对导致新冠肺炎的SARS-CoV-2病毒的免疫反应涉及免疫细胞和病毒抗原之间复杂的相互作用。CD19+淋巴细胞在驱动体液免疫反应中起着关键作用。在本研究中,使用串联质谱法进行高通量蛋白质组学分析,以研究6名健康个体和6名急性新冠肺炎患者的CD19+全细胞裂解物的蛋白质组学图谱的变化。火山图和热图显示了这两组之间蛋白质组学图谱的显著差异,表明与急性新冠肺炎相关的独特分子特征。富集分析,特别是使用Reactome数据库的过度表达分析(ORA)显示,参与中性粒细胞脱颗粒和干扰素α/β信号通路的蛋白质受到的影响最大,表明关键防御过程发生了变化。因此,这些发现为急性新冠肺炎中CD19+细胞反应的分子机制提供了新的见解。
{"title":"Initial high throughput proteomic analysis reveals alterations in CD19+ B lymphocyte profile in acute COVID-19 patients","authors":"Miroslav Marcin, Ondrej Zahornacký, Mária Kacírová, M. Sulíková, Miloslava Bajer-Ďuráčová, P. Rehulka, P. Bober, J. Fedacko, P. Jarčuška, J. Sabó","doi":"10.3389/av.2023.11702","DOIUrl":"https://doi.org/10.3389/av.2023.11702","url":null,"abstract":"The immune response to SARS-CoV-2, the virus responsible for COVID-19, involves intricate interactions between immune cells and viral antigens. CD19+ lymphocytes play a critical role in driving the humoral immune response. In this study, high-throughput proteomic analysis was performed using tandem mass spectrometry to investigate the changes in proteomic profiles of CD19+ whole cell lysates from 6 healthy individuals and 6 acute COVID-19 patients. The volcano plot and heat map showed significant differences in proteomic profiles between these two groups, indicating a distinct molecular signature associated with acute COVID-19. Enrichment analysis, especially over-representation analysis (ORA) using the Reactome database, revealed that proteins involved in neutrophil degranulation and interferon alpha/beta signaling pathways were among the most affected, indicating alterations in key defense processes. These findings, therefore, provide new insights into the molecular mechanisms underlying CD19+ cell responses in acute COVID-19.","PeriodicalId":7205,"journal":{"name":"Acta virologica","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45679641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In vitro antiviral activity of abietane diterpenoids isolated from Torreya nucifera against rotavirus infection 香榧abietane二萜体外抗轮状病毒感染活性的研究
IF 1.7 4区 医学 Q3 Medicine Pub Date : 2023-08-22 DOI: 10.3389/av.2023.11630
J. S. Park, J. Bae, J. Jung, Joong-Sun Kim, Su-Jin Park
Although vaccines have been developed for rotavirus infections, there is currently no effective therapeutic treatment. Therefore, this study aimed to evaluate the efficacy of 18-hydroxyferruginol (1) and 18-oxoferruginol (2) isolated from Torreya nucifera (T. nucifera) against bovine G8P[7] and porcine G5P[7] rotaviruses using two different assay strategies: 1) reduction of viral infectivity by neutralizing the virus (virucidal assay) and 2) inhibition of viral replication after infection (post-treatment assay). In the post-treatment assay, compounds 1 and 2 exhibited strong anti-rotavirus activity, with 50% effective concentration values of 24.7 μM (selectivity index; SI= 2.52) and 23.2 μM (SI= 1.75) against bovine G8P[7], 21.1 μM (SI= 2.95) and 22.6 μM (SI= 1.80) against porcine G5P[7], respectively. During viral replication, the two compounds demonstrated stronger inhibition of viral RNA synthesis in the late stages (18 h) than in the early stages (6 h). Compounds 1 and 2 also inhibited the synthesis of viral proteins such as VP6, as determined by immunofluorescence assay. Thus, it appears that compounds 1 and 2 isolated from T. nucifera possess strong antiviral activity against rotaviruses, inhibit viral replication, and may be developed into potential plant-derived therapeutic candidates against rotavirus infection.
尽管轮状病毒感染的疫苗已经开发出来,但目前还没有有效的治疗方法。因此,本研究旨在评估从香榧(T.nucifera)中分离的18-羟基铁酚(1)和18-氧代铁酚(2)对牛G8P[7]和猪G5P[7]轮状病毒的效力,使用两种不同的检测策略:1)通过中和病毒降低病毒感染性(杀病毒检测)和2)感染后抑制病毒复制(治疗后检测)。在处理后测定中,化合物1和2表现出较强的抗轮状病毒活性,对牛G8P[7]的50%有效浓度值分别为24.7μM(选择性指数;SI=2.52)和23.2μM(SI=1.75),对猪G5P[7]分别为21.1μM(SI=2.95)和22.6μM(SI=1.80)。在病毒复制过程中,这两种化合物在晚期(18小时)对病毒RNA合成的抑制作用比早期(6小时)更强。化合物1和2也抑制病毒蛋白如VP6的合成,如通过免疫荧光测定所测定的。因此,从T.nucifera分离的化合物1和2似乎对轮状病毒具有很强的抗病毒活性,抑制病毒复制,并可能发展成为潜在的植物来源的抗轮状病毒感染的候选治疗药物。
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