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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 Q4 VIROLOGY 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 Q4 VIROLOGY 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 Q4 VIROLOGY 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 Q4 VIROLOGY 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 Q4 VIROLOGY 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。
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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 Q4 VIROLOGY 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。
{"title":"In vitro antiviral activity of abietane diterpenoids isolated from Torreya nucifera against rotavirus infection","authors":"J. S. Park, J. Bae, J. Jung, Joong-Sun Kim, Su-Jin Park","doi":"10.3389/av.2023.11630","DOIUrl":"https://doi.org/10.3389/av.2023.11630","url":null,"abstract":"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.","PeriodicalId":7205,"journal":{"name":"Acta virologica","volume":"1 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45220133","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
Molecular characterization of multiple putative novel hepatitis B virus spliced DNA from a chronic hepatitis B patient 慢性乙型肝炎患者多种推测的新型乙型肝炎病毒剪接DNA的分子特征
IF 1.7 4区 医学 Q4 VIROLOGY Pub Date : 2023-07-04 DOI: 10.3389/av.2023.11663
Yihan Xiao, Zhigang Cui, Xiaojun Zhou, Zong-Hua Li, Lihua Li, Lixian Wu, Long Sun, Xiuji Cui
Spliced hepatitis B virus (HBV) RNA has been reported to affect the viral life cycle and progression of liver disease. As much as 30% of HBV RNA are spliced in infected cells, and some can be reverse transcribed to spliced DNA. To date, only a small number of spliced DNA have been identified and the majority require further investigation. This study aimed to identify the types of spliced DNA from the sera of a chronic hepatitis B patient. HBV DNA was isolated from the serum, and both full-length and spliced DNA were amplified by PCR. The amplified PCR products were then subcloned and sequenced using a Sanger sequence analysis. As a result, 19 types of spliced DNA were identified, 11 of which were assumed to be putative novel spliced DNA. These spliced DNA were doubly spliced with varied splice donor sites and splice acceptor sites. In addition to the frequently detected HBV SP1, SP2, and SP4, we also identified 11 putative novel spliced DNA in the serum. These findings indicate the complexity of HBV RNA splicing during viral life cycle.
剪接乙型肝炎病毒(HBV) RNA已被报道影响病毒生命周期和肝脏疾病的进展。多达30%的HBV RNA在感染细胞中被剪接,其中一些可以逆转录为剪接的DNA。到目前为止,只有一小部分剪接DNA被确定,大多数需要进一步研究。本研究旨在从慢性乙型肝炎患者的血清中鉴定剪接DNA的类型。从血清中分离HBV DNA,用PCR扩增全长DNA和剪接DNA。扩增的PCR产物随后进行亚克隆,并使用桑格序列分析进行测序。结果,鉴定出19种剪接DNA,其中11种被认为是假定的新剪接DNA。这些剪接的DNA通过不同的剪接供体位点和剪接受体位点进行双剪接。除了经常检测到的HBV SP1、SP2和SP4外,我们还在血清中发现了11种推测的新型剪接DNA。这些发现表明HBV RNA剪接在病毒生命周期中的复杂性。
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引用次数: 0
Influence of the SARS-CoV-2 Omicron (B.1.1.529) variant and booster vaccine doses on the seroprevalence of specific IgG antibodies in the staff of the Slovak Academy of Sciences SARS-CoV-2 Omicron (B.1.1.529)变体和加强疫苗剂量对斯洛伐克科学院工作人员特异性IgG抗体血清阳性率的影响
IF 1.7 4区 医学 Q4 VIROLOGY Pub Date : 2023-06-28 DOI: 10.3389/av.2023.11637
I. Kajanová, L. Jelenska, Ľ. Lukáčiková, Katarina Grossmannova, Martina Belisova, Nikola Istvanova, Natalia Gasparovicová, V. Zelník, S. Pastoreková, Z. Radiková, J. Kopáček
The presented seroprevalence study focused on specific antibodies to the SARS-CoV-2 virus is the second survey conducted among SAS employees. Its realization enabled monitoring of the impact of booster vaccination doses and the spread of the Omicron variant in a defined group of people. The total seropositivity of the involved SAS employees in autumn 2022 was 96.04%. In the group of vaccinated participants (1,189) the seropositivity rate was 99.5%, while among unvaccinated participants (176) it was 72.73%. By October 2022, when the study was conducted, 65.05% (888) of the participants have had a positive PCR/Ag test for SARS-CoV-2 at least once. Based on the presence of antibodies against the nucleoprotein (NCP) of SARS-CoV-2 it was proven, that 27.39% of participants (25.12% of vaccinated; 51.22% of non-vaccinated) who have never had a positive PCR/Ag test for SARS-CoV-2, overcame the COVID-19. According to self-assessment of the disease course, it was shown that a severe course occurred in 6.31% of the participants who overcame the disease without prior vaccination and in 1.44% of the participants who overcame COVID-19 after completing the baseline vaccination scheme. The most significant finding of the study is the evidence of significantly lower levels of specific antibodies after overcoming the Omicron variant of SARS-CoV-2, and thus its reduced immunogenicity compared to ancestral virus and earlier variants of concern.
这项针对SARS-CoV-2病毒特异性抗体的血清阳性率研究是在SAS员工中进行的第二次调查。它的实现使监测加强疫苗接种剂量的影响和欧米克隆变异在特定人群中的传播成为可能。2022年秋季SAS员工血清总阳性率为96.04%。接种组(1189人)血清阳性率为99.5%,未接种组(176人)血清阳性率为72.73%。到2022年10月进行这项研究时,65.05%(888)的参与者至少一次对SARS-CoV-2进行了PCR/Ag检测阳性。基于SARS-CoV-2核蛋白(NCP)抗体的存在,证明27.39%的参与者(25.12%的接种者;51.22%未接种疫苗的人(PCR/Ag检测从未呈阳性)克服了COVID-19。根据病程自我评估,未接种疫苗的患者中有6.31%出现严重病程,完成基线疫苗接种方案的患者中有1.44%出现严重病程。该研究最重要的发现是,在克服SARS-CoV-2的Omicron变体后,特异性抗体水平显着降低,因此与祖先病毒和早期受关注的变体相比,其免疫原性降低。
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引用次数: 0
Heat inactivation by high temperature as an approach to combat infections caused by airborne pathogens 高温灭活是一种对抗由空气传播的病原体引起的感染的方法
IF 1.7 4区 医学 Q4 VIROLOGY Pub Date : 2023-06-27 DOI: 10.3389/av.2023.11640
M. Sláviková, J. Strukova, B. Klempa, F. Simančík, S. Pastoreková, V. Zelník, J. Kopáček
The current pandemic of SARS-CoV-2 coronavirus infection has highlighted the importance of control measures to combat infections caused by airborne pathogens. Non-specific actions include various means of microorganism inactivation by chemical or physical methods targeting structural components of a given pathogen. Exposure of viruses and bacteria to elevated temperatures is one of the effective methods for discharging their harmful potential. Using a model of the Human Adenovirus 5 exposed to elevated temperatures with subsequent titration of the virus in vitro in A549 cells, we showed a dramatic decrease of the virus titer after heat treatment for 5 s at temperatures over 100°C. To verify the potential of the heat inactivation in a closed environment, the prototype of a high-capacity pathogen-cleaning device was constructed and tested. Application of the device for 2 h at an airflow rate of 900 m3/h in a room of 226 m3 reduced the total number of microorganisms in the air by more than 50% at all collection sites in the room.
当前严重急性呼吸系统综合征冠状病毒2型感染的大流行凸显了控制措施对抗空气传播病原体引起的感染的重要性。非特异性作用包括通过针对给定病原体的结构成分的化学或物理方法使微生物失活的各种手段。将病毒和细菌暴露在高温下是释放其有害潜能的有效方法之一。使用暴露于高温下的人类腺病毒5的模型,随后在A549细胞中对病毒进行体外滴定,我们发现在超过100°C的温度下热处理5 s后,病毒滴度显著降低。为了验证在封闭环境中热灭活的潜力,构建并测试了高容量病原体清洁装置的原型。在226立方米的房间中以900立方米/小时的气流速度应用该装置2小时,使房间中所有收集点的空气中微生物总数减少了50%以上。
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引用次数: 0
The modulation of metabolomics and antioxidant stress is involved in the effect of nitazoxanide against influenza A virus in vitro 代谢组学和抗氧化应激的调节参与了硝唑尼特抗甲型流感病毒的体外作用
IF 1.7 4区 医学 Q4 VIROLOGY Pub Date : 2023-06-23 DOI: 10.3389/av.2023.11612
Zhen Huang, Haihong Zheng, Yanping Wang, Xiao-yang Wang, Chunmei Wang, Yingchun Liu, Wen Zhou, Zhaoxiong Wang, Ke‐Zhi Zhang
The prevalence of highly infectious influenza A virus (IAV) is still a major threat to global human health. Nitazoxanide (NTZ) possesses potent antiviral properties against the influenza virus. However, the role of small molecular metabolites and antioxidant stress in the NTZ’s anti-influenza virus mechanism is not yet fully understood. This study compared the changes in cellular metabolism, ROS levels, antioxidant enzyme activities, and Keap-1/Nrf2 pathway in IAV-infected MDCK cells after NTZ treatment in vitro, using LC-MS-based metabolomics, flow cytometry, immunoblot. We observed that the NTZ treatment in the IAV-infected cells drastically altered the metabolism of small molecules, among which eleven metabolites were highly relevant to NTZ. The virus induced oxidative stress was also remarkably suppressed by NTZ. Meanwhile, the Nrf2 pathway and some proteins with modulating antiviral activity were activated after NTZ treatment, protecting cells from IAV injury. Therefore, regulation of the intracellular oxidative state is the primary outcome of NTZ treatment, which may underpin an antiviral mechanism attributed to the thiazolide.
高传染性甲型流感病毒(IAV)的流行仍然是对全球人类健康的主要威胁。Nitazoxanide (NTZ)对流感病毒具有有效的抗病毒特性。然而,小分子代谢物和抗氧化应激在NTZ抗流感病毒机制中的作用尚不完全清楚。本研究采用lc - ms代谢组学、流式细胞术、免疫印迹等方法,比较体外NTZ处理iav感染MDCK细胞后细胞代谢、ROS水平、抗氧化酶活性及Keap-1/Nrf2通路的变化。我们观察到,在iav感染的细胞中,NTZ处理显著改变了小分子的代谢,其中11种代谢物与NTZ高度相关。NTZ对病毒诱导的氧化应激也有显著的抑制作用。同时,NTZ处理后Nrf2通路和一些抗病毒活性调节蛋白被激活,保护细胞免受IAV损伤。因此,细胞内氧化状态的调节是NTZ治疗的主要结果,这可能是噻唑类药物抗病毒机制的基础。
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引用次数: 1
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