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Predicting changes in neutralizing antibody activity for SARS-CoV-2 XBB.1.5 using in silico protein modeling 利用硅蛋白模型预测SARS-CoV-2 XBB.1.5中和抗体活性的变化
Q4 VIROLOGY Pub Date : 2023-04-26 DOI: 10.3389/fviro.2023.1172027
Colby T. Ford, Shirish Yasa, Denis Jacob Machado, Richard Allen White, Daniel A. Janies
The SARS-CoV-2 variant XBB.1.5 is of concern as it has high transmissibility. XBB.1.5 currently accounts for upwards of 30% of new infections in the United States. One year after our group published the predicted structure of the Omicron (B.1.1.529) variant’s receptor binding domain (RBD) and antibody binding affinity, we return to investigate the new mutations seen in XBB.1.5 which is a descendant of Omicron. Using in silico modeling approaches against newer neutralizing antibodies that are shown effective against B.1.1.529, we predict the immune consequences of XBB.1.5’s mutations and show that there is no statistically significant difference in overall antibody evasion when comparing to the B.1.1.529 and other related variants (e.g., BJ.1 andBM.1.1.1). However, noticeable changes in antibody binding affinity were seen due to specific amino acid changes of interest in the newer variants.
SARS-CoV-2变体XBB.1.5具有高传播性,值得关注。XBB.1.5目前占美国新感染病例的30%以上。在我们小组发表了预测的Omicron (B.1.1.529)变体的受体结合域(RBD)结构和抗体结合亲和力一年后,我们回到研究在Omicron的后代XBB.1.5中发现的新突变。使用针对新的中和抗体的计算机建模方法,对B.1.1.529有效,我们预测了XBB.1.5突变的免疫后果,并表明与B.1.1.529和其他相关变体(例如,BJ.1和bm .1.1.1)相比,总体抗体逃避没有统计学上的显著差异。然而,抗体结合亲和力的显著变化是由于新变异中感兴趣的特定氨基酸的变化。
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引用次数: 0
Molecular characterization of dengue virus serotype 1 infections in French travelers from Africa between 2013 and 2019 2013年至2019年来自非洲的法国旅行者中登革热病毒血清1型感染的分子特征
Q4 VIROLOGY Pub Date : 2023-04-20 DOI: 10.3389/fviro.2023.1124848
T. Fourié, G. Durand, F. Touret, G. Piorkowski, A. Dubot-Pérès, X. D. de Lamballerie, I. Leparc-Goffart, G. Grard
Laboratory-confirmed dengue virus (DENV) infections in Africa are rarely reported. In this study, we report 18 DENV serotype 1 (DENV-1) infections, diagnosed by the French National Reference Center for Arboviruses, in patients who had histories of recent travel in Africa. Our analyses revealed two cases, one from Niger in 2018 and one from the Republic of the Congo in 2016, where dengue fever had not been previously reported, and one case from Mauritania in 2015, where DENV-1 had not been previously reported. These cases support the reported spread of DENV outside its well-established tropical and subtropical environment toward the arid deserts of the Sahel. Phylogenetic analyses suggest that a single monophyletic DENV-1 lineage is currently in circulation in West Africa, having spread from East Africa after its original importation from Asia. Our study provides an improved understanding of DENV dynamics in Africa and underlines the importance of surveillance of travel-acquired infections.
在非洲很少报告实验室确诊的登革热病毒感染。在这项研究中,我们报告了18例由法国国家虫媒病毒参考中心诊断的DENV血清1型(DENV-1)感染病例,这些患者近期有非洲旅行史。我们的分析发现了两例病例,一例来自2018年的尼日尔,一例来自2016年的刚果共和国,此前未报告登革热,另一例来自2015年的毛里塔尼亚,此前未报告DENV-1。这些病例支持所报告的DENV在其既定的热带和亚热带环境之外向萨赫勒干旱沙漠传播。系统发育分析表明,单一的单系DENV-1谱系在最初从亚洲输入后从东非传播,目前在西非流行。我们的研究提高了对非洲DENV动态的理解,并强调了监测旅行获得性感染的重要性。
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引用次数: 2
Regulation of viral RNA-dependent RNA polymerases by phosphorylation 磷酸化对病毒RNA依赖RNA聚合酶的调控
Q4 VIROLOGY Pub Date : 2023-04-06 DOI: 10.3389/fviro.2023.1176840
Camille Duflos, T. Michiels
RNA viruses encode an RNA-dependent RNA polymerase (RdRp), which is essential for transcription and replication of their genome since host cells lack equivalent enzymes. RdRp residues were shown to be phosphorylated by host kinases in several human, animal or plant viruses including flaviviruses, picornaviruses, coronaviruses, influenza viruses and tymoviruses. RdRps can be phosphorylated on several residues by distinct host kinases. Phosphomimetic mutations of identified phosphorylated residues either positively or negatively regulate RNA synthesis or association of RdRps with RNA or other proteins. Interestingly, some RdRps evolved to recruit cellular kinases through direct protein-protein interaction, likely to promote or to tightly control their own phosphorylation. Given the essential nature of RdRps for RNA virus replication, a better knowledge of RdRps’ phosphorylation is expected to facilitate the design of future drugs that strongly affect polymerase activity.
RNA病毒编码RNA依赖性RNA聚合酶(RdRp),由于宿主细胞缺乏等效的酶,RdRp对其基因组的转录和复制至关重要。在几种人类、动物或植物病毒中,RdRp残基被宿主激酶磷酸化,包括黄病毒、小核糖核酸病毒、冠状病毒、流感病毒和鼓室病毒。RdRps可以在几个残基上被不同的宿主激酶磷酸化。已鉴定的磷酸化残基的拟磷突变正向或负向调节RNA合成或RdRps与RNA或其他蛋白质的结合。有趣的是,一些RdRps进化为通过直接的蛋白质-蛋白质相互作用募集细胞激酶,可能促进或严格控制其自身的磷酸化。鉴于RdRps对RNA病毒复制的本质,更好地了解RdRps的磷酸化有望促进未来强烈影响聚合酶活性的药物的设计。
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引用次数: 0
Co-detection of respiratory syncytial virus with other respiratory viruses across all age groups before and during the COVID-19 pandemic 在COVID-19大流行之前和期间对所有年龄组的呼吸道合胞病毒与其他呼吸道病毒进行联合检测
Q4 VIROLOGY Pub Date : 2023-03-24 DOI: 10.3389/fviro.2023.1156012
Haya Hayek, Justin Z. Amarin, Yasmeen Z. Qwaider, A. Khanfar, Tess Stopczynski, J. Schmitz, J. Chappell, J. Wrenn, A. Spieker, N. Halasa, L. Howard
Background Patterns of respiratory syncytial virus (RSV) co-detection with other viruses may have been disrupted during the coronavirus disease 2019 (COVID-19) pandemic, but the clinical impact of viral co-detections with RSV is not well-established. We aimed to explore the frequency and clinical outcomes associated with RSV single detection and co-detection before and during the pandemic. Methods We conducted a single-center retrospective cohort study of all children and adults with respiratory samples tested using a respiratory pathogen panel (RPP; 01/01/2018–11/30/2022), a provider-ordered polymerase chain reaction–based assay that detects respiratory pathogens. We stratified our cohort into age groups: 0–4, 5–17, 18–64, and ≥65 years old. Among RSV-positive samples, we compared the proportion of samples with single RSV detection before and during the pandemic and the patterns of specific viral co-detections. We compared the odds of hospitalization, oxygen use, intensive care unit admission, and intubation between individuals with RSV single detection and those with co-detection. Results Among 57,940 samples collected during the study period, 3,986 (6.9%) were RSV-positive. RSV was co-detected with at least one other virus in 1,231/3,158 (39.0%), 104/348 (29.9%), 49/312 (15.7%), and 21/168 (12.5%) of samples from individuals 0–4, 5–17, 18–64, and ≥65 years old, respectively. The relative frequencies of RSV single detection and co-detection were comparable before and during the pandemic except in children 0–4 years old, in whom single RSV detections were more prevalent before (63.7%) than during (59.5%) the pandemic (p=0.021). In children 0–4 years old, RSV co-detection was associated with lower odds of hospitalization compared to single RSV detection, and RSV co-detection with parainfluenza viruses or human rhinovirus/enterovirus was associated with significantly lower odds of hospitalization, while RSV/SARS-CoV-2 co-detection was associated with higher odds of ICU admission. In adults ≥65 years old, RSV co-detection was associated with lower odds of oxygen use. Conclusion The proportion of RSV co-detection did not appreciably vary before and during the pandemic, except in young children, though the combinations of co-detected viruses did vary. Our findings suggest that the clinical impact of RSV co-detection with other viruses may be age-associated and virus-specific.
在2019冠状病毒病(COVID-19)大流行期间,呼吸道合胞病毒(RSV)与其他病毒共检测的模式可能已被破坏,但病毒与RSV共检测的临床影响尚未确定。我们的目的是探讨大流行前和大流行期间RSV单一检测和联合检测的频率和临床结果。方法:我们对所有儿童和成人进行了一项单中心回顾性队列研究,使用呼吸道病原体面板(RPP;2018年1月1日- 2022年11月30日),这是一种由供应商订购的基于聚合酶链反应的检测方法,可检测呼吸道病原体。我们将队列分层为年龄组:0-4岁、5-17岁、18-64岁和≥65岁。在RSV阳性样本中,我们比较了大流行前和大流行期间检测到单一RSV的样本比例以及特定病毒共同检测的模式。我们比较了单独检测RSV和同时检测RSV的患者的住院率、吸氧率、重症监护病房入院率和插管率。结果在57940份样本中,rsv阳性3986份(6.9%)。在0-4岁、5-17岁、18-64岁和≥65岁的人群中,分别有1231 / 3158(39.0%)、104/348(29.9%)、49/312(15.7%)和21/168(12.5%)与RSV共检出至少一种其他病毒。除0-4岁儿童外,流行前和流行期间RSV单检和共检的相对频率具有可比性,0-4岁儿童流行前(63.7%)高于流行期间(59.5%)(p=0.021)。在0-4岁儿童中,与单一RSV检测相比,RSV共检测与住院的几率较低,RSV与副流感病毒或人鼻病毒/肠道病毒共检测与住院的几率显著较低,而RSV/SARS-CoV-2共检测与ICU住院的几率较高。在≥65岁的成年人中,RSV联合检测与较低的氧气使用几率相关。结论除幼儿外,RSV共检比例在大流行前和大流行期间没有明显变化,但共检病毒组合存在差异。我们的研究结果表明,RSV与其他病毒共同检测的临床影响可能与年龄相关且病毒特异性。
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引用次数: 1
Identification of surfactin as an anti-severe fever with thrombocytopenia syndrome virus multi-target compound extracted from the culture broth of marine microbes 海洋微生物培养液中提取的抗严重发热伴血小板减少综合征病毒多靶点化合物表面活性素的鉴定
Q4 VIROLOGY Pub Date : 2023-03-07 DOI: 10.3389/fviro.2022.1064265
Shuzo Urata, Jun Takouda, Yoshihiro Watanabe, M. Sakaguchi, Yasuteru Sakurai, Y. Inahashi, M. Iwatsuki, J. Yasuda, Yoshimasa Tanaka, K. Takeda
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus first identified in China in 2011 and later reported in other Asian countries. Significant efforts have been made to develop anti-SFTSV compounds; however, there are no approved vaccines or antivirals against SFTSV infections. Marine organisms provide nearly unlimited biological resources to produce therapeutic drugs for the treatment and control of disease. In this study, we aimed to identify anti-SFTSV chemical compounds from the culture broth extracts of marine microbes collected from the coasts of the Nagasaki Prefecture, Japan. Of the 80 extracts, two showed an anti-SFTSV effect. One of them, which exhibited low cell toxicity, was used for further characterization. Chemical analysis combined with the anti-SFTSV effect identified surfactin as one of the main components of the selected extract. Our study showed a proof-of-concept to identify novel antiviral compounds from marine microbes against the virus of interest. Further analysis showed that surfactin affected the integrity of the virion membrane and inhibited SFTSV infection-induced membrane fusion at low pH conditions. Furthermore, surfactin inhibits the post-entry step of viral replication in the cell, which is a novel mode of antiviral action of surfactin. These results indicate that surfactin can target multiple steps of SFTSV replication in cells.
严重发热伴血小板减少综合征病毒(SFTSV)是一种蜱传病毒,2011年首次在中国发现,后来在其他亚洲国家报道。已经做出了重大努力来开发抗SFTSV的化合物;然而,目前还没有批准的针对SFTSV感染的疫苗或抗病毒药物。海洋生物提供了几乎无限的生物资源来生产用于治疗和控制疾病的治疗药物。在本研究中,我们旨在从日本长崎县海岸采集的海洋微生物培养液提取物中鉴定抗SFTSV的化合物。在80种提取物中,有两种显示出抗SFTSV的作用。其中一种表现出低细胞毒性,用于进一步表征。化学分析和抗SFTSV作用相结合,确定表面活性素是所选提取物的主要成分之一。我们的研究表明,从海洋微生物中鉴定出新的抗病毒化合物可以对抗感兴趣的病毒。进一步的分析表明,在低pH条件下,表面活性素影响病毒粒子膜的完整性,并抑制SFTSV感染诱导的膜融合。此外,表面活性素抑制病毒在细胞中复制的进入后步骤,这是表面活性素抗病毒作用的一种新模式。这些结果表明,表面活性素可以靶向细胞中SFTSV复制的多个步骤。
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引用次数: 0
Oral intake of heat-killed Lactiplantibacillus pentosus ONRICb0240 partially protects mice against SARS-CoV-2 infection 口服热灭活乳酸菌ONRICb0240可部分保护小鼠免受SARS-CoV-2感染
Q4 VIROLOGY Pub Date : 2023-03-06 DOI: 10.3389/fviro.2023.1137133
Maki Kiso, R. Uraki, Mutsumi Ito, S. Yamayoshi, Yoshifumi Kotani, M. Imai, N. Kohda, Y. Kawaoka
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing coronavirus pandemic. Besides vaccines and antiviral drugs, probiotics have attracted attention for prevention of SARS-CoV-2 infection. Here, we examined the efficacy of heat-killed Lactiplantibacillus pentosus ONRICb0240 (b240) against SARS-CoV-2 infection in mice. We observed that oral intake of heat-killed b240 did not affect virus titers in the respiratory organs of SARS-CoV-2-infected mice, but did provide partial protection against SARS-CoV-2 infection. In addition, heat-killed b240 treatment suppressed the expression of IL-6, a key proinflammatory cytokine, on Day 2 post-infection. Our results highlight the promising protective role of heat-killed b240 and suggest a possible mechanism by which heat-killed b240 partially protects against SARS-CoV-2 infection by modulating host responses.
严重急性呼吸系统综合征冠状病毒2型是持续的冠状病毒大流行的原因。除了疫苗和抗病毒药物外,益生菌在预防严重急性呼吸系统综合征冠状病毒2型感染方面也引起了关注。在这里,我们检测了热灭活的戊型乳酸杆菌ONRICb0240(b240)对小鼠感染严重急性呼吸系统综合征冠状病毒2型的疗效。我们观察到,口服热灭活b240不会影响感染严重急性呼吸系统综合征冠状病毒2型的小鼠呼吸器官中的病毒滴度,但确实对严重急性呼吸系冠状病毒2型感染提供了部分保护。此外,热杀b240治疗在感染后第2天抑制了IL-6的表达,IL-6是一种关键的促炎细胞因子。我们的研究结果强调了热杀死的b240有前景的保护作用,并提出了一种可能的机制,通过这种机制,热杀死的b240通过调节宿主反应来部分预防严重急性呼吸系统综合征冠状病毒2型感染。
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引用次数: 0
Epitope mapping of SARS-CoV-2 spike protein differentiates the antibody binding activity in vaccinated and infected individuals SARS-CoV-2刺突蛋白表位定位可区分疫苗接种者和感染者的抗体结合活性
Q4 VIROLOGY Pub Date : 2023-03-03 DOI: 10.3389/fviro.2023.988109
Nathaniel Felbinger, D. Trudil, L. Loomis, R. Ascione, G. Siragusa, S. Haba, Shruti Rastogi, Aidan Mucci, Mark Claycomb, Sebastian Snowberger, B. Luke, S. Francesconi, Shirley Tsang
Previous studies have attempted to characterize the antibody response of individuals to the SARS-CoV-2 virus on a linear peptide level by utilizing peptide microarrays. These studies have helped to identify epitopes that have potential to be used for diagnostic tests to identify infected individuals. The immunological responses of individuals who have received the two most popular vaccines available in the US, the Moderna mRNA-1273 or the Pfizer BNT162b2 mRNA vaccines, have not been characterized. We aimed to identify linear peptides of the SARS-CoV-2 spike protein that elicited high IgG or IgA binding activity and to compare the immunoreactivity of infected individuals to those who received both doses of either vaccine by utilizing peptide microarrays. Our results revealed peptide epitopes of significant IgG binding among recently infected individuals. Some of these peptides are located near variable regions of the receptor binding domains as well as the conserved region in the c-terminal of the spike protein implicated in the high infectivity of SARS-CoV-2. Vaccinated individuals lacked a response to these distinct markers despite the overall antibody binding activity being similar.
先前的研究试图利用肽微阵列在线性肽水平上表征个体对SARS-CoV-2病毒的抗体反应。这些研究有助于确定表位,这些表位有可能用于诊断测试,以识别受感染的个体。接种了美国最流行的两种疫苗(Moderna mRNA-1273或Pfizer BNT162b2 mRNA疫苗)的个体的免疫反应尚未确定。我们的目的是鉴定引起高IgG或IgA结合活性的SARS-CoV-2刺突蛋白的线性肽,并利用肽微阵列比较感染个体与接受两种剂量疫苗的个体的免疫反应性。我们的结果显示肽表位显著IgG结合最近感染的个体。其中一些肽位于受体结合域的可变区域附近,以及与SARS-CoV-2高传染性有关的刺突蛋白c端的保守区域。尽管总体抗体结合活性相似,但接种疫苗的个体对这些不同的标记物缺乏反应。
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引用次数: 0
Willingness to accept COVID-19 vaccine and its determinants in Ethiopia: A systematic review and meta-analysis 埃塞俄比亚人接受COVID-19疫苗的意愿及其决定因素:系统回顾和荟萃分析
Q4 VIROLOGY Pub Date : 2023-03-03 DOI: 10.3389/fviro.2023.1065991
Tadesse Tolossa, Getahun Fetensa, Bikila Regassa Feyisa, B. Wakuma, Matiyos Lema
Introduction Vaccination is one of the most crucial strategies in the control of pandemics such as COVID-19. Although a couple of research has been conducted to assess the willingness of the population to accept the COVID-19 vaccine, the findings are inconsistent and inconclusive. This study aimed to assess the pooled willingness to uptake the COVID-19 vaccine and its determinants in Ethiopia. Methods Published and unpublished articles were accessed from various electronic databases and digital libraries. A random-effects model was used to estimate the pooled effect size with a 95% confidence interval. Inverse variance (I2) was used to visualize the presence of heterogeneity. Publication bias was assessed using funnel plots and Egger’s statistical test. Results A total of 2345 studies were identified from several databases and 16 studies fulfilled the eligibility criteria and were included in the final meta-analysis. The pooled magnitude of willingness to accept the COVID-19 vaccine in Ethiopia was 55.19% (95% CI: 42.91, 67.48). The current meta-analysis indicated that age greater than 25 years (OR=1.49, 95% CI: 1.12, 1.98) and having a good attitude towards the COVID-19 vaccine (3.57, 95% CI: 1.46, 8.72) were significantly associated with the COVID-19 vaccine uptake. Conclusions and recommendations In general, the magnitude of the COVID-19 vaccine acceptance rate among the public is unacceptably low in Ethiopia. Therefore, there is a need to build public trust through the provision of reliable and consistent information about vaccines using different media outlets.
疫苗接种是控制COVID-19等大流行的最关键战略之一。尽管已经进行了一些研究来评估人们接受COVID-19疫苗的意愿,但研究结果并不一致,也没有定论。本研究旨在评估埃塞俄比亚接种COVID-19疫苗的总体意愿及其决定因素。方法从各种电子数据库和数字图书馆检索已发表和未发表的文章。采用随机效应模型估计合并效应大小,置信区间为95%。反方差(I2)用于显示异质性的存在。采用漏斗图和Egger统计检验评估发表偏倚。结果从多个数据库中共筛选出2345项研究,其中16项研究符合入选标准,并被纳入最终的荟萃分析。埃塞俄比亚接受COVID-19疫苗的总意愿值为55.19% (95% CI: 42.91, 67.48)。目前的荟萃分析显示,年龄大于25岁(OR=1.49, 95% CI: 1.12, 1.98)和对COVID-19疫苗持良好态度(3.57,95% CI: 1.46, 8.72)与COVID-19疫苗的吸收率显著相关。总体而言,埃塞俄比亚公众对COVID-19疫苗的接受率低得令人无法接受。因此,有必要通过利用不同的媒体渠道提供关于疫苗的可靠和一致的信息来建立公众信任。
{"title":"Willingness to accept COVID-19 vaccine and its determinants in Ethiopia: A systematic review and meta-analysis","authors":"Tadesse Tolossa, Getahun Fetensa, Bikila Regassa Feyisa, B. Wakuma, Matiyos Lema","doi":"10.3389/fviro.2023.1065991","DOIUrl":"https://doi.org/10.3389/fviro.2023.1065991","url":null,"abstract":"Introduction Vaccination is one of the most crucial strategies in the control of pandemics such as COVID-19. Although a couple of research has been conducted to assess the willingness of the population to accept the COVID-19 vaccine, the findings are inconsistent and inconclusive. This study aimed to assess the pooled willingness to uptake the COVID-19 vaccine and its determinants in Ethiopia. Methods Published and unpublished articles were accessed from various electronic databases and digital libraries. A random-effects model was used to estimate the pooled effect size with a 95% confidence interval. Inverse variance (I2) was used to visualize the presence of heterogeneity. Publication bias was assessed using funnel plots and Egger’s statistical test. Results A total of 2345 studies were identified from several databases and 16 studies fulfilled the eligibility criteria and were included in the final meta-analysis. The pooled magnitude of willingness to accept the COVID-19 vaccine in Ethiopia was 55.19% (95% CI: 42.91, 67.48). The current meta-analysis indicated that age greater than 25 years (OR=1.49, 95% CI: 1.12, 1.98) and having a good attitude towards the COVID-19 vaccine (3.57, 95% CI: 1.46, 8.72) were significantly associated with the COVID-19 vaccine uptake. Conclusions and recommendations In general, the magnitude of the COVID-19 vaccine acceptance rate among the public is unacceptably low in Ethiopia. Therefore, there is a need to build public trust through the provision of reliable and consistent information about vaccines using different media outlets.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42909130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Visualisation of microalgal-viral interactions by high-speed atomic force microscopy 用高速原子力显微镜观察微藻与病毒的相互作用
Q4 VIROLOGY Pub Date : 2023-03-02 DOI: 10.3389/fviro.2023.1111335
Christopher T Evans, O. Payton, L. Picco, M. Allen
Visualization of viruses and their hosts has been paramount to their study and understanding. The direct observation of the morphological dynamics of infection is a highly desired capability and the focus of instrument development across a variety of microscopy technologies. This study demonstrates progress that has been made in exploiting the capabilities offered by HS-AFM to characterise the interactions between coccolithoviruses and their globally important coccolithophore hosts. We observe whole Emiliania huxleyi Virus capsids, transient binding to Emiliania huxleyi derived supported lipid bilayers, and host-virus binding in real-time in an environmentally relevant, aqueous environment.
病毒及其宿主的可视化对他们的研究和理解至关重要。直接观察感染的形态动力学是一种非常理想的能力,也是各种显微镜技术中仪器开发的重点。这项研究证明了在利用HS-AFM提供的能力来表征球石病毒与其全球重要的球石宿主之间的相互作用方面取得的进展。我们在与环境相关的水性环境中实时观察到整个艾米莉安娜·胡克斯利病毒衣壳、与艾米莉安娜·哈克斯利衍生的负载脂质双层的瞬时结合以及宿主病毒的结合。
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引用次数: 0
Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses. 在SARS-CoV-2中和抗体反应中频繁使用IGHV3-30-3。
Q4 VIROLOGY Pub Date : 2023-03-01 DOI: 10.3389/fviro.2023.1128253
Pradeepa Pushparaj, Andrea Nicoletto, Xaquin Castro Dopico, Daniel J Sheward, Sungyong Kim, Simon Ekström, Ben Murrell, Martin Corcoran, Gunilla B Karlsson Hedestam

The antibody response to SARS-CoV-2 shows biased immunoglobulin heavy chain variable (IGHV) gene usage, allowing definition of genetic signatures for some classes of neutralizing antibodies. We investigated IGHV gene usage frequencies by sorting spike-specific single memory B cells from individuals infected with SARS-CoV-2 early in the pandemic. From two study participants and 703 spikespecific B cells, the most used genes were IGHV1-69, IGHV3-30-3, and IGHV3-30. Here, we focused on the IGHV3-30 group of genes and an IGHV3-30-3-using ultrapotent neutralizing monoclonal antibody, CAB-F52, which displayed broad neutralizing activity also in its germline-reverted form. IGHV3-30-3 is encoded by a region of the IGH locus that is highly variable at both the allelic and structural levels. Using personalized IG genotyping, we found that 4 of 14 study participants lacked the IGHV3-30-3 gene on both chromosomes, raising the question if other, highly similar IGHV genes could substitute for IGHV3-30-3 in persons lacking this gene. In the context of CAB-F52, we found that none of the tested IGHV3-33 alleles, but several IGHV3-30 alleles could substitute for IGHV3-30-3, suggesting functional redundancy between the highly homologous IGHV3-30 and IGHV3-30-3 genes for this antibody.

对SARS-CoV-2的抗体反应显示有偏倚的免疫球蛋白重链变量(IGHV)基因使用,允许定义某些类别的中和抗体的遗传特征。我们通过在大流行早期从SARS-CoV-2感染者中分选刺特异性单记忆B细胞来调查IGHV基因的使用频率。从两名研究参与者和703个尖刺特异性B细胞中,最常用的基因是IGHV1-69、IGHV3-30-3和IGHV3-30。在这里,我们重点研究了IGHV3-30组基因和使用超强中和单克隆抗体CAB-F52的IGHV3-30-3,该单克隆抗体在其种系恢复形式中也显示出广泛的中和活性。IGHV3-30-3是由IGH位点的一个区域编码的,该区域在等位基因和结构水平上都是高度可变的。通过个性化IG基因分型,我们发现14名研究参与者中有4人在两条染色体上都缺乏IGHV3-30-3基因,这就提出了一个问题,即其他高度相似的IGHV基因是否可以替代缺乏该基因的人的IGHV3-30-3。在CAB-F52的背景下,我们发现所有测试的IGHV3-33等位基因都不能替代IGHV3-30-3,但有几个IGHV3-30等位基因可以替代IGHV3-30-3,这表明该抗体高度同源的IGHV3-30和IGHV3-30-3基因之间存在功能冗余。
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引用次数: 0
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