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Virus-vectoring thrips regulate the excessive multiplication of tomato spotted wilt virus using their antiviral immune responses. 病毒载体蓟马利用其抗病毒免疫反应调节番茄斑萎病毒的过度繁殖。
IF 3.8 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-05-01 DOI: 10.1099/jgv.0.001984
Eeshita Mandal, Falguni Khan, Eui-Joon Kil, Yonggyun Kim

The tomato spotted wilt virus (TSWV) is a member of the Tospoviridae family and has an negative/ambisense single-stranded RNA genome. Frankliniella occidentalis and F. intonsa are known to be dominant pests in Capsicum annuum (hot pepper) and can cause damage to the plant either directly by feeding, or indirectly by transmitting TSWV in a persistent and propagative manner, resulting in serious economic damage. This study compared the immune responses of two different thrips species against TSWV infection by transcriptome analysis, which then allowed the assessment of antiviral responses using RNA interference (RNAi). Both adult thrips shared about 90 % of the transcripts in non-viruliferous conditions. Most signal components of the immune pathways were shared by these two thrips species, and their expression levels fluctuated differentially in response to TSWV infection at early immature stages. The functional assays using RNAi treatments indicated that the Toll and JAK/STAT pathways were associated with the antiviral responses, but the IMD pathway was not. The upregulation of dorsal switch protein one supported its physiological role in recognizing TSWV infection and triggering the eicosanoid biosynthetic pathway, which mediates melanization and apoptosis in thrips. In addition, the signal components of the RNAi pathways fluctuated highly after TSWV infection. Individual RNAi treatments specific to the antiviral signalling and response components led to significant increases in the TSWV amount in the thrips, causing virus-induced mortality. These findings suggest that immune signalling pathways leading to antiviral responses are operating in the thrips to regulate TSWV litres to prevent a fatal viral overload. This study also indicates the differential antiviral responses between the TSWV-transmitting F. occidentalis and F. intonsa.

番茄斑枯病病毒(TSWV)是 Tospoviridae 家族的成员,具有阴性/反义单链 RNA 基因组。众所周知,Frankliniella occidentalis 和 F. intonsa 是辣椒(Capsicum annuum)的主要害虫,它们会直接取食或间接传播 TSWV,对植物造成损害,导致严重的经济损失。本研究通过转录组分析比较了两种不同蓟马对 TSWV 感染的免疫反应,然后利用 RNA 干扰(RNAi)评估了抗病毒反应。在无病毒条件下,两种成蓟马共享约 90% 的转录本。这两种蓟马共享免疫途径中的大多数信号成分,它们的表达水平在未成熟早期对 TSWV 感染的反应中出现不同程度的波动。使用 RNAi 处理进行的功能测试表明,Toll 和 JAK/STAT 通路与抗病毒反应有关,但 IMD 通路与之无关。背侧开关蛋白 1 的上调支持了其在识别 TSWV 感染和触发二十烷类生物合成途径(介导蓟马黑色化和凋亡)中的生理作用。此外,RNAi 途径的信号成分在 TSWV 感染后波动很大。针对抗病毒信号和反应元件的单个 RNAi 处理会导致蓟马体内的 TSWV 量显著增加,从而导致病毒诱导的死亡。这些发现表明,导致抗病毒反应的免疫信号通路在蓟马体内运行,以调节 TSWV 升数,防止致命的病毒超载。这项研究还表明,传播 TSWV 的 F. occidentalis 和 F. intonsa 之间存在不同的抗病毒反应。
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引用次数: 0
Decoding huge phage diversity: a taxonomic classification of Lak megaphages. 解码巨型噬菌体的多样性:拉克巨型噬菌体的分类法。
IF 3.6 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-05-01 DOI: 10.1099/jgv.0.001997
Ryan Cook, Marco A Crisci, Hannah V Pye, Andrea Telatin, Evelien M Adriaenssens, Joanne M Santini

High-throughput sequencing for uncultivated viruses has accelerated the understanding of global viral diversity and uncovered viral genomes substantially larger than any that have so far been cultured. Notably, the Lak phages are an enigmatic group of viruses that present some of the largest known phage genomes identified in human and animal microbiomes, and are dissimilar to any cultivated viruses. Despite the wealth of viral diversity that exists within sequencing datasets, uncultivated viruses have rarely been used for taxonomic classification. We investigated the evolutionary relationships of 23 Lak phages and propose a taxonomy for their classification. Predicted protein analysis revealed the Lak phages formed a deeply branching monophyletic clade within the class Caudoviricetes which contained no other phage genomes. One of the interesting features of this clade is that all current members are characterised by an alternative genetic code. We propose the Lak phages belong to a new order, the 'Grandevirales'. Protein and nucleotide-based analyses support the creation of two families, three sub-families, and four genera within the order 'Grandevirales'. We anticipate that the proposed taxonomy of Lak megaphages will simplify the future classification of related viral genomes as they are uncovered. Continued efforts to classify divergent viruses are crucial to aid common analyses of viral genomes and metagenomes.

对未培养病毒的高通量测序加快了人们对全球病毒多样性的了解,并发现了比迄今为止培养的病毒大得多的病毒基因组。值得注意的是,拉克噬菌体是一个神秘的病毒群,在人类和动物微生物组中发现了一些已知最大的噬菌体基因组,它们与任何栽培病毒都不同。尽管测序数据集中存在丰富的病毒多样性,但未培养的病毒很少被用于分类学分类。我们研究了 23 种湖泊噬菌体的进化关系,并提出了分类方法。蛋白质预测分析表明,Lak噬菌体在Caudoviricetes类中形成了一个分支很深的单系支系,该支系不包含其他噬菌体基因组。该支系的一个有趣特点是,目前的所有成员都具有另一种遗传密码。我们建议拉克噬菌体属于一个新的纲--"Grandevirales"。基于蛋白质和核苷酸的分析支持在 "Grandevirales "目中建立两个科、三个亚科和四个属。我们预计,所提出的拉克巨型病毒分类法将简化未来发现的相关病毒基因组的分类。继续努力对不同的病毒进行分类对于帮助病毒基因组和元基因组的共同分析至关重要。
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引用次数: 0
Molecular mechanisms behind the generation of pro-oncogenic HIV-1 matrix protein p17 variants 产生促致癌 HIV-1 基质蛋白 p17 变体背后的分子机制
IF 3.8 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-30 DOI: 10.1099/jgv.0.001982
Alberto Zani, Serena Messali, Antonella Bugatti, Matteo Uggeri, Alessandro Rondina, Leonardo Sclavi, Francesca Caccuri and Arnaldo Caruso
HIV-1 matrix protein p17 variants (vp17s), characterized by amino acid insertions at the COOH-terminal region of the viral protein, have been recently identified and studied for their biological activity. Different from their wild-type counterpart (refp17), vp17s display a potent B cell growth and clonogenic activity. Recent data have highlighted the higher prevalence of vp17s in people living with HIV-1 (PLWH) with lymphoma compared with those without lymphoma, suggesting that vp17s may play a key role in lymphomagenesis. Molecular mechanisms involved in vp17 development are still unknown. Here we assessed the efficiency of HIV-1 Reverse Transcriptase (RT) in processing this genomic region and highlighted the existence of hot spots of mutation in Gag, at the end of the matrix protein and close to the matrix-capsid junction. This is possibly due to the presence of inverted repeats and palindromic sequences together with a high content of Adenine in the 322–342 nucleotide portion, which constrain HIV-1 RT to pause on the template. To define the recombinogenic properties of hot spots of mutation in the matrix gene, we developed plasmid vectors expressing Gag and a minimally modified Gag variant, and measured homologous recombination following cell co-nucleofection by next-generation sequencing. Data obtained allowed us to show that a wide range of recombination events occur in concomitance with the identified hot spots of mutation and that imperfect events may account for vp17s generation.
艾滋病毒-1基质蛋白p17变体(vp17s)的特点是在病毒蛋白的COOH-末端区域插入氨基酸,最近发现了这些变体,并对其生物活性进行了研究。与野生型对应物(refp17)不同,vp17s 具有强大的 B 细胞生长和克隆活性。最近的数据显示,在患有淋巴瘤的 HIV-1 感染者(PLWH)中,vp17s 的发病率高于未患淋巴瘤的感染者,这表明 vp17s 可能在淋巴瘤的发生中起着关键作用。参与 vp17 形成的分子机制尚不清楚。在这里,我们评估了 HIV-1 逆转录酶(RT)处理该基因组区域的效率,并强调了在基质蛋白末端和靠近基质-噬菌体交界处的 Gag 中存在突变热点。这可能是由于在 322–342 核苷酸部分存在倒位重复序列和回文序列以及高含量的腺嘌呤,这些因素限制了 HIV-1 RT 在模板上的暂停。为了确定基质基因突变热点的重组特性,我们开发了表达 Gag 和最小修饰 Gag 变体的质粒载体,并通过新一代测序法测量了细胞共核转染后的同源重组。获得的数据使我们能够证明,与已确定的突变热点同时发生的重组事件范围很广,不完善的事件可能是产生 vp17s 的原因。
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引用次数: 0
ICTV Virus Taxonomy Profile: Nairoviridae 2024 ICTV 病毒分类简介:奈洛病毒科 2024
IF 3.8 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-30 DOI: 10.1099/jgv.0.001974
Jens H. Kuhn, Sergey V. Alkhovsky, Tatjana Avšič-Županc, Éric Bergeron, Felicity Burt, Koray Ergünay, Aura R. Garrison, Marco Marklewitz, Ali Mirazimi, Anna Papa, Janusz T. Pawęska, Jessica R. Spengler and Gustavo Palacios
Nairoviridae is a family for negative-sense RNA viruses with genomes of about 17.2–21.1 kb. These viruses are maintained in and/or transmitted by arthropods among birds, reptiles and mammals. Norwaviruses and orthonairoviruses can cause febrile illness in humans. Several orthonairoviruses can infect mammals, causing mild, severe and sometimes, fatal diseases. Nairovirids produce enveloped virions containing two or three single-stranded RNA segments with open reading frames that encode a nucleoprotein (N), sometimes a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Nairoviridae, which is available at www.ictv.global/report/nairoviridae.
奈洛病毒科(Nairoviridae)是一个基因组约为 17.2–21.1 kb 的负义 RNA 病毒科。这些病毒在鸟类、爬行动物和哺乳动物中通过节肢动物维持和/或传播。诺瓦克病毒和原脊病毒可导致人类发热性疾病。有几种正奈洛韦病毒可感染哺乳动物,引起轻微、严重、有时甚至致命的疾病。奈洛病毒产生的包膜病毒含有两个或三个具有开放阅读框的单链 RNA 片段,这些片段编码一个核蛋白(N),有时是一个糖蛋白前体(GPC),以及一个含有 RNA 定向 RNA 聚合酶(RdRP)结构域的大蛋白(L)。本文是国际病毒分类委员会(ICTV)关于奈洛病毒科的报告摘要,可在 www.ictv.global/report/nairoviridae 网站上查阅。
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引用次数: 0
HCMV US2 co-opts TRC8 to degrade the endoplasmic reticulum-resident protein LMAN2L HCMV US2 与 TRC8 合作降解内质网驻留蛋白 LMAN2L
IF 3.8 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-30 DOI: 10.1099/jgv.0.001980
Leah M. Hunter, Joanne Kite, Alice Fletcher-Etherington, Katie Nightingale, Luis Nobre, Robin Antrobus, Ceri A. Fielding, Richard J. Stanton and Michael P. Weekes
The human cytomegalovirus (HCMV) pUS2 glycoprotein exploits the host’s endoplasmic reticulum (ER)-associated degradation (ERAD) pathway to degrade major histocompatibility complex class I (MHC-I) and prevent antigen presentation. Beyond MHC-I, pUS2 has been shown to target a range of cellular proteins for degradation, preventing their cell surface expression. Here we have identified a novel pUS2 target, ER-resident protein lectin mannose binding 2 like (LMAN2L). pUS2 expression was both necessary and sufficient for the downregulation of LMAN2L, which was dependent on the cellular E3 ligase TRC8. Given the hypothesized role of LMAN2L in the trafficking of glycoproteins, we employed proteomic plasma membrane profiling to measure LMAN2L-dependent changes at the cell surface. A known pUS2 target, integrin alpha-6 (ITGA6), was downregulated from the surface of LMAN2L-deficient cells, but not other integrins. Overall, these results suggest a novel strategy of pUS2-mediated protein degradation whereby pUS2 targets LMAN2L to impair trafficking of ITGA6. Given that pUS2 can directly target other integrins, we propose that this single viral protein may exhibit both direct and indirect mechanisms to downregulate key cell surface molecules.
人类巨细胞病毒(HCMV)的 pUS2 糖蛋白利用宿主内质网(ER)相关降解(ERAD)途径降解主要组织相容性复合体 I 类(MHC-I),阻止抗原呈递。除 MHC-I 外,pUS2 还能靶向降解一系列细胞蛋白,阻止它们在细胞表面表达。pUS2 的表达对 LMAN2L 的下调既是必要的也是充分的,而 LMAN2L 的下调依赖于细胞 E3 连接酶 TRC8。鉴于 LMAN2L 在糖蛋白运输中的假设作用,我们采用了蛋白质组质膜剖析来测量细胞表面依赖于 LMAN2L 的变化。已知的 pUS2 靶标--整合素α-6 (ITGA6) 在 LMAN2L 缺失的细胞表面下调,但其他整合素没有下调。总之,这些结果表明了一种 pUS2 介导的蛋白质降解新策略,即 pUS2 以 LMAN2L 为靶标,从而影响 ITGA6 的运输。鉴于 pUS2 可直接靶向其他整合素,我们认为这种单一病毒蛋白可能具有直接和间接机制来下调关键细胞表面分子。
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引用次数: 0
ICTV Virus Taxonomy Profile: Fusariviridae 2024 ICTV 病毒分类简介:Fusariviridae 2024
IF 3.8 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-15 DOI: 10.1099/jgv.0.001973
Sotaro Chiba, Nobuhiro Suzuki, Leonardo Velasco, María A. Ayllón, Shin-Yi Lee-Marzano, Liying Sun, Sead Sabanadzovic and Massimo Turina
Fusariviridae is a family of mono-segmented, positive-sense RNA viruses with genome sizes of 5.9–10.7 kb. Most genomic RNAs are bicistronic, but exceptions have up to four predicted ORFs. In bicistronic genomes, the 5′-proximal ORF codes for a single protein with both RNA-directed RNA polymerase (RdRP) and RNA helicase (Hel) domains; little is known about the protein encoded by the second ORF. Fusarivirids do not appear to form virions. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Fusariviridae, which is available at ictv.global/report/fusariviridae.
Fusariviridae 是单节段正义 RNA 病毒科,基因组大小为 5.9–10.7 kb。大多数基因组 RNA 都是双链的,但也有例外,有多达四个预测 ORF。在双螺旋基因组中,5′-近端 ORF 编码一个具有 RNA 定向 RNA 聚合酶(RdRP)和 RNA 螺旋酶(Hel)结构域的蛋白质;第二个 ORF 编码的蛋白质鲜为人知。Fusarivirids 似乎不会形成病毒。本文是国际病毒分类委员会(ICTV)关于 Fusariviridae 科的报告摘要,可在 ictv.global/report/fusariviridae 网站上查阅。
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引用次数: 0
Molecular and biological characterization of a bunyavirus infecting the brown planthopper (Nilaparvata lugens) 感染褐飞虱(Nilaparvata lugens)的布尼亚病毒的分子和生物学特征
IF 3.8 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-11 DOI: 10.1099/jgv.0.001977
Ting Li, Zhuang-Xin Ye, Ke-Hui Feng, Qian-Zhuo Mao, Qing-Ling Hu, Ji-Chong Zhuo, Chuan-Xi Zhang, Jian-Ping Chen and Jun-Min Li
A negative-strand symbiotic RNA virus, tentatively named Nilaparvata lugens Bunyavirus (NLBV), was identified in the brown planthopper (BPH, Nilaparvata lugens). Phylogenetic analysis indicated that NLBV is a member of the genus Mobuvirus (family Phenuiviridae, order Bunyavirales). Analysis of virus-derived small interfering RNA suggested that antiviral immunity of BPH was successfully activated by NLBV infection. Tissue-specific investigation showed that NLBV was mainly accumulated in the fat-body of BPH adults. Moreover, NLBV was detected in eggs of viruliferous female BPHs, suggesting the possibility of vertical transmission of NLBV in BPH. Additionally, no significant differences were observed for the biological properties between NLBV-infected and NLBV-free BPHs. Finally, analysis of geographic distribution indicated that NLBV may be prevalent in Southeast Asia. This study provided a comprehensive characterization on the molecular and biological properties of a symbiotic virus in BPH, which will contribute to our understanding of the increasingly discovered RNA viruses in insects.
在褐跳虫(BPH,Nilaparvata lugens)中发现了一种负链共生RNA病毒,暂命名为Nilaparvata lugens Bunyavirus(NLBV)。系统进化分析表明,NLBV属于Mobuvirus属(Phenuiviridae科,Bunyavirales目)。对病毒衍生小干扰 RNA 的分析表明,BPH 的抗病毒免疫被 NLBV 感染成功激活。组织特异性研究表明,NLBV 主要积聚在 BPH 成虫的脂肪体内。此外,在带毒雌性 BPH 的卵中也检测到了 NLBV,这表明 NLBV 有可能在 BPH 中垂直传播。此外,受 NLBV 感染的 BPH 与未受 NLBV 感染的 BPH 在生物学特性上没有明显差异。最后,地理分布分析表明,NLBV 可能在东南亚流行。这项研究全面描述了一种共生病毒在 BPH 中的分子和生物学特性,这将有助于我们了解昆虫中发现的越来越多的 RNA 病毒。
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引用次数: 0
ICTV Virus Taxonomy Profile: Hantaviridae 2024 ICTV 病毒分类简介:汉坦病毒科 2024
IF 3.8 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-08 DOI: 10.1099/jgv.0.001975
Steven B. Bradfute, Charles H. Calisher, Boris Klempa, Jonas Klingström, Jens H. Kuhn, Lies Laenen, Nicole D. Tischler and Piet Maes
Hantaviridae is a family for negative-sense RNA viruses with genomes of about 10.5–14.6 kb. These viruses are maintained in and/or transmitted by fish, reptiles, and mammals. Several orthohantaviruses can infect humans, causing mild, severe, and sometimes-fatal diseases. Hantavirids produce enveloped virions containing three single-stranded RNA segments with open reading frames that encode a nucleoprotein (N), a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Hantaviridae, which is available at ictv.global/report/hantaviridae.
汉他病毒科(Hantaviridae)是一个基因组约为 10.5–14.6 kb 的负义 RNA 病毒科。这些病毒存在于鱼类、爬行动物和哺乳动物体内,并由它们传播。有几种正汉坦病毒可感染人类,导致轻微、严重、有时甚至致命的疾病。汉坦病毒产生的包膜病毒含有三个具有开放阅读框的单链 RNA 片段,分别编码核蛋白 (N)、糖蛋白前体 (GPC) 和含有 RNA 定向 RNA 聚合酶 (RdRP) 结构域的大蛋白 (L)。本文是国际病毒分类委员会(ICTV)关于汉坦病毒科的报告摘要,可在 ictv.global/report/hantaviridae 网站上查阅。
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引用次数: 0
Translational arrest and mRNA decay are independent activities of alphaherpesvirus virion host shutoff proteins 翻译抑制和 mRNA 衰变是阿尔法疱疹病毒病毒宿主关闭蛋白的独立活动
IF 3.8 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-04 DOI: 10.1099/jgv.0.001976
Lucy Eke, Alistair Tweedie, Sophie Cutts, Emma L. Wise and Gillian Elliott
The herpes simplex virus 1 (HSV1) virion host shutoff (vhs) protein is an endoribonuclease that regulates the translational environment of the infected cell, by inducing the degradation of host mRNA via cellular exonuclease activity. To further understand the relationship between translational shutoff and mRNA decay, we have used ectopic expression to compare HSV1 vhs (vhsH) to its homologues from four other alphaherpesviruses – varicella zoster virus (vhsV), bovine herpesvirus 1 (vhsB), equine herpesvirus 1 (vhsE) and Marek’s disease virus (vhsM). Only vhsH, vhsB and vhsE induced degradation of a reporter luciferase mRNA, with poly(A)+ insitu hybridization indicating a global depletion of cytoplasmic poly(A)+ RNA and a concomitant increase in nuclear poly(A)+ RNA and the polyA tail binding protein PABPC1 in cells expressing these variants. By contrast, vhsV and vhsM failed to induce reporter mRNA decay and poly(A)+ depletion, but rather, induced cytoplasmic G3BP1 and poly(A)+ mRNA- containing granules and phosphorylation of the stress response proteins eIF2α and protein kinase R. Intriguingly, regardless of their apparent endoribonuclease activity, all vhs homologues induced an equivalent general blockade to translation as measured by single-cell puromycin incorporation. Taken together, these data suggest that the activities of translational arrest and mRNA decay induced by vhs are separable and we propose that they represent sequential steps of the vhs host interaction pathway.
单纯疱疹病毒 1(HSV1)病毒宿主关闭(vhs)蛋白是一种内切核酸酶,它通过细胞外切核酸酶活性诱导宿主 mRNA 的降解,从而调节感染细胞的翻译环境。为了进一步了解翻译关闭与 mRNA 降解之间的关系,我们利用异位表达将 HSV1 vhs(vhsH)与其他四种α-疱疹病毒的同源物进行了比较:水痘带状疱疹病毒(vhsV)、牛疱疹病毒 1(vhsB)、马疱疹病毒 1(vhsE)和马立克氏病病毒(vhsM)。只有 vhsH、vhsB 和 vhsE 能诱导荧光素酶 mRNA 报告基因的降解,poly(A)+ 原位杂交表明,在表达这些变体的细胞中,细胞质 poly(A)+ RNA 全球耗竭,同时细胞核 poly(A)+ RNA 和 polyA 尾结合蛋白 PABPC1 增加。相比之下,vhsV 和 vhsM 未能诱导报告基因 mRNA 的衰变和 poly(A)+ 的耗竭,反而诱导了细胞质 G3BP1 和含有颗粒的 poly(A)+ mRNA 以及应激反应蛋白 eIF2α 和蛋白激酶 R 的磷酸化。耐人寻味的是,不管它们的内切核酸酶活性如何,所有 vhs 同源物都能诱导等效的翻译总体阻滞,这是用单细胞嘌呤霉素掺入法测定的。总之,这些数据表明,vhs 诱导的翻译受阻和 mRNA 衰变活动是可分离的,我们认为它们代表了 vhs 宿主相互作用途径的连续步骤。
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引用次数: 0
Cardiac glycosides inhibit early and late vaccinia virus protein expression. 强心苷抑制早期和晚期疫苗病毒蛋白的表达
IF 3.8 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-03-01 DOI: 10.1099/jgv.0.001971
Jerzy Samolej, Ian J White, Blair L Strang, Jason Mercer

Cardiac glycosides (CGs) are natural steroid glycosides, which act as inhibitors of the cellular sodium-potassium ATPase pump. Although traditionally considered toxic to human cells, CGs are widely used as drugs for the treatment of cardiovascular-related medical conditions. More recently, CGs have been explored as potential anti-viral drugs and inhibit replication of a range of RNA and DNA viruses. Previously, a compound screen identified CGs that inhibited vaccinia virus (VACV) infection. However, no further investigation of the inhibitory potential of these compounds was performed, nor was there investigation of the stage(s) of the poxvirus lifecycle they impacted. Here, we investigated the anti-poxvirus activity of a broad panel of CGs. We found that all CGs tested were potent inhibitors of VACV replication. Our virological experiments showed that CGs did not impact virus infectivity, binding, or entry. Rather, experiments using recombinant viruses expressing reporter proteins controlled by VACV promoters and arabinoside release assays demonstrated that CGs inhibited early and late VACV protein expression at different concentrations. Lack of virus assembly in the presence of CGs was confirmed using electron microscopy. Thus, we expand our understanding of compounds with anti-poxvirus activity and highlight a yet unrecognized mechanism by which poxvirus replication can be inhibited.

强心苷(CGs)是一种天然甾体苷,是细胞钠钾 ATP 酶泵的抑制剂。虽然传统上认为强心苷对人体细胞有毒,但它被广泛用作治疗心血管相关疾病的药物。最近,人们又将 CGs 探索为潜在的抗病毒药物,它能抑制一系列 RNA 和 DNA 病毒的复制。此前,通过化合物筛选发现了可抑制疫苗病毒(VACV)感染的 CGs。但是,没有对这些化合物的抑制潜力进行进一步研究,也没有对它们影响痘病毒生命周期的哪个阶段进行研究。在此,我们研究了一系列 CG 的抗痘病毒活性。我们发现,所有测试的 CG 都是 VACV 复制的强效抑制剂。我们的病毒学实验表明,CGs 不会影响病毒的感染性、结合或进入。相反,使用表达由 VACV 启动子控制的报告蛋白的重组病毒进行的实验和阿拉伯糖苷释放实验表明,不同浓度的 CGs 可抑制早期和晚期 VACV 蛋白的表达。电子显微镜证实,在 CGs 存在的情况下,病毒不会组装。因此,我们扩大了对具有抗痘病毒活性的化合物的认识,并强调了一种尚未认识到的抑制痘病毒复制的机制。
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引用次数: 0
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