The Journal of general virology最新文献

英文中文

Phosphorylation of the Autographa californica multiple nucleopolyhedrovirus polyhedron envelope protein plays an important role in the formation of the occlusion body envelope. 加州签名虫多核多面体包膜蛋白的磷酸化在闭塞体包膜的形成中起重要作用。

IF 3.8

The Journal of general virology

Pub Date : 2022-06-01 DOI: 10.1099/jgv.0.001759

Jia Wang, Jian Yang, Chengfeng Lei, Xiulian Sun, Jia Hu

During the life cycle of a baculovirus, a crystallized protein matrix, formed by polyhedrin (POLH), is produced. The protein matrix is surrounded by a multilayered protein/carbohydrate envelope, and matrix and envelope together form a mature occlusion body (OB). The polyhedron envelope plays an important role in resistance against adverse external environments. The polyhedron envelope protein (PEP) is the main protein that forms the polyhedron envelope, but the mechanism of formation of the polyhedron envelope is unclear. Here, through immunofluorescence localization observations, we found that PEP interacted with both POLH and P10 during formation of the polyhedron envelope in the late stages of infection, and PEP was also required for P10 incorporation on the surface of OBs. In this process, the phosphorylation of PEP played an important role. PEP was determined to be a phosphorylated protein using the Phos-tag technique, and PK1 was determined to be the phosphokinase of PEP by co-immunoprecipitation and in vitro phosphorylation. Immunofluorescence localization revealed that PEP was continuously phosphorylated by PK1 after PEP entered the nucleus until PEP was correctly packaged on the OB surface. Multi-point mutations of PEP conservative potential phosphorylation sites showed that the simultaneous mutation of S85, T86 and Y92 caused changes in the location of PEP and P10 in the late stages of infection, and resulted in an OB surface that lacked the polyhedron envelope. These data suggested that the phosphorylation of PEP at particular sites, i.e. S85, T86 and Y92, plays an important role in the formation of the polyhedron envelope.

在杆状病毒的生命周期中，产生由多面蛋白(POLH)形成的结晶蛋白基质。蛋白质基质被多层蛋白质/碳水化合物包膜包围，基质和包膜共同形成成熟的闭塞体(OB)。多面体包膜在抵抗外界不利环境方面起着重要作用。多面体包膜蛋白(polyhedron envelope protein, PEP)是形成多面体包膜的主要蛋白，但其形成机制尚不清楚。这里，通过免疫荧光定位观察，我们发现PEP在感染后期多面体包膜形成过程中与POLH和P10相互作用，PEP也需要P10结合到OBs表面。在这一过程中，PEP的磷酸化发挥了重要作用。利用Phos-tag技术确定PEP为磷酸化蛋白，通过共免疫沉淀和体外磷酸化确定PK1为PEP的磷酸化激酶。免疫荧光定位显示PEP进入细胞核后被PK1持续磷酸化，直到PEP被正确包装在OB表面。PEP保守潜在磷酸化位点多点突变表明，S85、T86和Y92同时突变导致感染后期PEP和P10的位置发生变化，导致OB表面缺乏多面体包膜。这些数据表明PEP在特定位点(S85, T86和Y92)的磷酸化在多面体包膜的形成中起重要作用。

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引用次数: 0

Establishment of a reverse genetics system for avian rotavirus A strain PO-13. 禽轮状病毒a株PO-13反向遗传系统的建立。

IF 3.8

The Journal of general virology

Pub Date : 2022-06-01 DOI: 10.1099/jgv.0.001760

Marika Kanda, Saori Fukuda, Nanami Hamada, Shoko Nishiyama, Tatsunori Masatani, Yuji Fujii, Fumiki Izumi, Misuzu Okajima, Koki Taniguchi, Makoto Sugiyama, Satoshi Komoto, Naoto Ito

Avian rotavirus A (RVA) is one of major enteric pathogens that cause diarrhoea in young avian individuals. Importantly, some of the avian RVA strains of G18P[17] genotype are naturally transmitted to and cause clinical diseases in mammalian species, indicating their potential risks to animal health. Although molecular information on the pathogenesis by avian RVA strains will be useful for estimating their risks, the absence of a reverse genetics (RG) system for these strains has hindered the elucidation of their pathogenic mechanisms. In this study, we aimed to establish an RG system for the avian G18P[17] prototype strain PO-13, which was isolated from a pigeon in Japan in 1983 and was experimentally shown to be pathogenic in suckling mice. Transfection with plasmids expressing 11 genomic RNA segments of the strain resulted in rescue of the infectious virus with an artificially introduced genetic marker on its genome, indicating that an RG system for the PO-13 strain was successfully established. The rescued recombinant strain rPO-13 had biological properties almost identical to those of its wild-type strain (wtPO-13). Notably, both rPO-13 and wtPO-13 induced diarrhoea in suckling mice with similar efficiencies. It was thus demonstrated that the RG system will be useful for elucidating the pathogenic mechanisms of the PO-13 strain at the molecular level. This is the first report of the establishment of an RG system for an avian RVA strain.

禽轮状病毒A (RVA)是引起雏鸟腹泻的主要肠道病原体之一。重要的是，一些G18P[17]基因型的禽RVA菌株可以自然传播给哺乳动物并引起临床疾病，这表明它们对动物健康存在潜在风险。虽然禽RVA毒株致病机理的分子信息将有助于估计其风险，但缺乏这些毒株的反向遗传(RG)系统阻碍了对其致病机制的阐明。在本研究中，我们旨在建立鸟类G18P[17]原型菌株PO-13的RG系统，该菌株于1983年从日本的一只鸽子中分离出来，实验证明在哺乳小鼠中具有致病性。用表达该病毒11个基因组RNA片段的质粒转染后，在其基因组上人工引入遗传标记，成功地建立了PO-13病毒的RG系统。重组菌株rPO-13的生物学特性与野生菌株wtPO-13基本相同。值得注意的是，rPO-13和wtPO-13在哺乳小鼠中诱导腹泻的效率相似。因此，RG系统将有助于在分子水平上阐明PO-13菌株的致病机制。这是建立禽RVA毒株RG系统的首次报道。

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引用次数: 4

Corrigendum: Mutational analysis of the helicase domain of a replication initiator protein reveals critical roles of Lys 272 of the B' motif and Lys 289 of the β-hairpin loop in geminivirus replication. 更正:复制启动蛋白解旋酶结构域的突变分析揭示了B'基序的Lys 272和β-发夹环的Lys 289在双病毒复制中的关键作用。

The Journal of general virology

Pub Date : 2022-05-01 DOI: 10.1099/jgv.0.001753

B. George, Rajrani Ruhel, Mohit Mazumder, V. Sharma, S. Jain, S. Gourinath, S. Chakraborty

引用次数: 0

ICTV Virus Taxonomy Profile: Polymycoviridae 2022. ICTV病毒分类概况:多分枝病毒科

The Journal of general virology

Pub Date : 2022-05-01 DOI: 10.1099/jgv.0.001747

I. Kotta-Loizou, R. Coutts, Ictv Report Consortium

Members of the family Polymycoviridae are small viruses with multi-segmented and non-conventionally encapsidated double-stranded (ds) RNA genomes. Typically, polymycoviruses have four genomic segments, although some have up to eight. The genus Polymycovirus includes several species whose members infect fungi (ascomycetes and basidiomycetes), and oomycetes, altering host morphology, sporulation, growth and virulence. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Polymycoviridae, which is available at ictv.global/report/polymycoviridae.

多分枝病毒科的成员是具有多节段和非传统封装的双链RNA基因组的小病毒。通常，多分枝病毒有四个基因组片段，尽管有些有多达八个。多分枝病毒属包括若干种，其成员感染真菌(子囊菌和担子菌)和卵菌，改变宿主形态、产孢、生长和毒力。这是国际病毒分类委员会(ICTV)关于多分枝病毒科报告的摘要，该报告可在ICTV .global/ Report / Polymycoviridae找到。

引用次数: 13

Non-canonical nematode endogenous retroviruses resulting from RNA virus glycoprotein gene capture by a metavirus. 由RNA病毒糖蛋白基因被元病毒捕获而产生的非典型线虫内源性逆转录病毒。

The Journal of general virology

Pub Date : 2022-05-01 DOI: 10.1099/jgv.0.001739

M. Sacco, Jonathan Lau, D. Godinez-Vidal, I. Kaloshian

Reverse-transcribing retroviruses exist as horizontally transmitted infectious agents or vertically transmitted endogenous retroviruses (ERVs) resident in eukaryotic genomes, and they are phylogenetically related to the long terminal repeat (LTR) class of retrotransposons. ERVs and retrotransposons are often distinguished only by the presence or absence of a gene encoding the envelope glycoprotein (env). Endogenous elements of the virus family Metaviridae include the insect-restricted Errantivirus genus of ERVs, for which some members possess env, and the pan-eukaryotic Metavirus genus that lacks an envelope glycoprotein gene. Here we report a novel Nematoda endogenous retrovirus (NERV) clade with core retroviral genes arranged uniquely as a continuous gag-env-pro-pol ORF. Reverse transcriptase sequences were phylogenetically related to metaviruses, but envelope glycoprotein sequences resembled those of the Nyamiviridae and Chrysoviridae RNA virus families, suggesting env gene capture during host cell infection by an RNA virus. NERVs were monophyletic, restricted to the nematode subclass Chromadoria, and included additional ORFs for a small hypothetical protein or a large Upf1-like RNA-dependent AAA-ATPase/helicase indicative of viral transduction of a host gene. Provirus LTR identity, low copy number, ORF integrity and segregation of three loci in Meloidogyne incognita, taken together with detection of NERV transcriptional activity, support potential infectivity of NERVs, along with their recent emergence and integration. Altogether, NERVs constitute a new and distinct Metaviridae lineage demonstrating retroviral evolution through sequential heterologous gene capture events.

逆转录逆转录病毒作为水平传播的感染因子或垂直传播的内源性逆转录病毒(erv)存在于真核生物基因组中，它们与长末端重复序列(LTR)类逆转录转座子在系统发育上相关。erv和反转录转座子通常仅通过编码包膜糖蛋白(env)基因的存在或不存在来区分。病毒科元病毒科的内源性元素包括erv的昆虫限制性Errantivirus属，其中一些成员具有env，以及缺乏包膜糖蛋白基因的泛真核元病毒属。在这里，我们报道了一个新的线虫内源性逆转录病毒(NERV)分支，其核心逆转录病毒基因独特地排列为一个连续的gag-env-pro-pol ORF。逆转录酶序列在系统发育上与中间病毒相关，但包膜糖蛋白序列与纳米病毒科和黄病毒科RNA病毒家族相似，提示在宿主细胞被RNA病毒感染时捕获了env基因。神经网络是单系的，局限于线虫亚纲Chromadoria，并包括一个小的假设蛋白或一个大的upf1样rna依赖的aaa - atp酶/解旋酶的额外的orf，指示病毒转导宿主基因。原病毒LTR的一致性、低拷贝数、ORF的完整性和三个基因座的分离，再加上对神经病毒转录活性的检测，支持了神经病毒的潜在感染性，以及它们最近的出现和整合。总之，NERVs构成了一个新的和独特的元病毒科谱系，通过顺序的异源基因捕获事件显示逆转录病毒进化。

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引用次数: 0

Rotavirus incapable of NSP6 expression can cause diarrhea in suckling mice. 不能表达NSP6的轮状病毒可引起哺乳小鼠腹泻。

The Journal of general virology

Pub Date : 2022-05-01 DOI: 10.1099/jgv.0.001745

Saori Fukuda, M. Kugita, Y. Higashimoto, K. Shiogama, Hanako Tsujikawa, Kyoko Moriguchi, N. Ito, M. Sugiyama, S. Nagao, T. Murata, K. Taniguchi, S. Komoto

The group A rotavirus (RVA) genome comprising 11 double-stranded RNAs encodes six structural proteins (VP1-VP4, VP6, and VP7) and six non-structural proteins (NSP1-NSP6). Among these 12 rotaviral proteins, NSP6 has been less studied as to its function. We previously prepared a recombinant NSP6-deficient RVA derived from simian strain SA11-L2 by reverse genetics, and found that the NSP6-deficient virus grew well in cell culture, although its growth was less abundant than that of the parental SA11-L2 strain. In this study, we examined the potency of a recombinant RVA incapable of NSP6 expression to cause diarrhoea in suckling mice. The suckling mice infected with the NSP6-deficient virus apparently experienced diarrhoea, although the symptom was milder and the duration of diarrhoea was shorter than in the mice infected with the authentic SA11-L2 strain. Thus, together with the results obtained for cultured cells in the previous study, it can be concluded that NSP6 is not necessarily required for replication and pathogenicity in vitro and in vivo.

A组轮状病毒(RVA)基因组由11个双链rna组成，编码6个结构蛋白(VP1-VP4、VP6和VP7)和6个非结构蛋白(NSP1-NSP6)。在这12种轮状病毒蛋白中，对NSP6的功能研究较少。我们之前通过反向遗传从类人猿菌株SA11-L2中制备了重组nsp6缺陷RVA，并发现nsp6缺陷病毒在细胞培养中生长良好，尽管其生长量不如亲本菌株SA11-L2。在这项研究中，我们检测了不能表达NSP6的重组RVA在哺乳小鼠中引起腹泻的效力。感染nsp6缺陷病毒的哺乳小鼠明显出现腹泻，尽管症状较轻，腹泻持续时间较感染SA11-L2菌株的小鼠短。因此，结合前人在培养细胞中获得的结果，可以得出结论，在体外和体内，NSP6并不一定是复制和致病性所必需的。

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引用次数: 1

Rotavirus exploits SREBP pathway for hyper lipid biogenesis during replication. 轮状病毒在复制过程中利用SREBP途径进行高脂生物生成。

The Journal of general virology

Pub Date : 2022-05-01 DOI: 10.1099/jgv.0.001757

A. Naveed, Muhammad Ammar Naveed, Lubna Akram, Muhammad Sharif, Mun-Il Kang, Sang-Ik Park

Species A rotavirus (RVA) is one of the pathogens causing severe acute gastroenteritis in young children and animals worldwide. RVA replicates and assembles its immature particle within electron dense compartments known as viroplasm. Despite the importance of lipid droplet (LD) formation in the RVA viroplasm, the upstream molecules modulating LD formation have remained elusive. Here, we demonstrate that RVA infection reprogrammes sterol regulatory element binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells. Interestingly, silencing of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny virus production. Moreover, knockout of SREBP-1c gene conferred resistance to RVA-induced diarrhoea, reduction of RVA replication, and mitigation of small intestinal pathology in mice. This study identifies SREBPs-mediated lipogenic reprogramming in RVA-infected host cells for facilitating virus replication and SREBPs as a potential target for developing therapeutics against RVA infection.

A种轮状病毒(RVA)是世界范围内引起幼儿和动物严重急性胃肠炎的病原体之一。RVA在称为病毒质的电子密集区室中复制和组装其未成熟颗粒。尽管脂滴(LD)的形成在RVA病毒质中具有重要意义，但调节LD形成的上游分子仍然是难以捉摸的。在这里，我们证明了RVA感染重新编程了病毒感染细胞中依赖于固醇调节元件结合蛋白(SREBPs)的脂肪生成途径。有趣的是，SREBPs的沉默显著降低了RVA蛋白的合成、基因组复制和子代病毒的产生。此外，敲除SREBP-1c基因可使小鼠抵抗RVA诱导的腹泻，减少RVA复制，并减轻小肠病理。本研究确定了SREBPs介导的RVA感染宿主细胞中的脂质重编程，以促进病毒复制，并将SREBPs作为开发抗RVA感染治疗方法的潜在靶点。

引用次数: 1

Serum and cerebrospinal fluid phosphorylated neurofilament heavy subunit as a marker of neuroaxonal damage in tick-borne encephalitis. 血清和脑脊液磷酸化的神经丝重亚基作为蜱传脑炎神经轴突损伤的标志。

The Journal of general virology

Pub Date : 2022-05-01 DOI: 10.1099/jgv.0.001743

Andrea Fořtová, V. Hönig, Martin Palus, J. Salát, M. Pýchová, L. Krbková, T. Vyhlídalová, M. Kriha, A. Chrdle, D. Růžek

Extensive axonal and neuronal loss is the main cause of severe manifestations and poor outcomes in tick-borne encephalitis (TBE). Phosphorylated neurofilament heavy subunit (pNF-H) is an essential component of axons, and its detection in cerebrospinal fluid (CSF) or serum can indicate the degree of neuroaxonal damage. We examined the use of pNF-H as a biomarker of neuroaxonal injury in TBE. In 89 patients with acute TBE, we measured CSF levels of pNF-H and 3 other markers of brain injury (glial fibrillary acidic protein, S100B and ubiquitin C-terminal hydrolase L1) and compared the results to those for patients with meningitis of other aetiology and controls. Serum pNF-H levels were measured in 80 patients and compared with findings for 90 healthy blood donors. TBE patients had significantly (P<0.001) higher CSF pNF-H levels than controls as early as hospital admission. Serum pNF-H concentrations were significantly higher in samples from TBE patients collected at hospital discharge (P<0.0001) than in controls. TBE patients with the highest peak values of serum pNF-H, exceeding 10 000 pg ml-1, had a very severe disease course, with coma or tetraplegia. Patients requiring intensive care had significantly higher serum pNF-H levels than other TBE patients (P<0.01). Elevated serum pNF-H values were also observed in patients with incomplete recovery (P<0.05). Peak serum pNF-H levels correlated positively with the duration of hospitalization (P=0.005). Measurement of pNF-H levels in TBE patients might be useful for assessing disease severity and determining prognosis.

广泛的轴突和神经元丧失是蜱传脑炎(TBE)严重表现和预后不良的主要原因。磷酸化神经丝重亚单位(phospylated neurofilament heavy subunit, pNF-H)是轴突的重要组成部分，其在脑脊液或血清中的检测可提示神经轴突的损伤程度。我们研究了pNF-H作为脑出血神经轴突损伤的生物标志物的使用。在89例急性TBE患者中，我们测量了脑脊液中pNF-H和其他3种脑损伤标志物(胶质纤维酸性蛋白、S100B和泛素c端水解酶L1)的水平，并将结果与其他病因的脑膜炎患者和对照组进行了比较。研究人员测量了80名患者的血清pNF-H水平，并与90名健康献血者的结果进行了比较。早在入院时，脑出血患者的脑脊液pNF-H水平就显著高于对照组(P<0.001)。出院时收集的TBE患者血清pNF-H浓度显著高于对照组(P<0.0001)。血清pNF-H峰值超过10000 pg ml-1的be患者病程非常严重，可出现昏迷或四肢瘫痪。重症监护患者血清pNF-H水平明显高于其他TBE患者(P<0.01)。不完全恢复患者血清pNF-H值升高(P<0.05)。峰值血清pNF-H水平与住院时间呈正相关(P=0.005)。测量TBE患者的pNF-H水平可能有助于评估疾病严重程度和确定预后。

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引用次数: 3

Nanobodies in the limelight: Multifunctional tools in the fight against viruses. 纳米体引人注目:对抗病毒的多功能工具。

The Journal of general virology

Pub Date : 2022-05-01 DOI: 10.1099/jgv.0.001731

Ainhoa Moliner-Morro, G. McInerney, L. Hanke

Antibodies are natural antivirals generated by the vertebrate immune system in response to viral infection or vaccination. Unsurprisingly, they are also key molecules in the virologist's molecular toolbox. With new developments in methods for protein engineering, protein functionalization and application, smaller antibody-derived fragments are moving in focus. Among these, camelid-derived nanobodies play a prominent role. Nanobodies can replace full-sized antibodies in most applications and enable new possible applications for which conventional antibodies are challenging to use. Here we review the versatile nature of nanobodies, discuss their promise as antiviral therapeutics, for diagnostics, and their suitability as research tools to uncover novel aspects of viral infection and disease.

抗体是脊椎动物免疫系统对病毒感染或疫苗接种产生的天然抗病毒药物。不出所料，它们也是病毒学家分子工具箱中的关键分子。随着蛋白质工程、蛋白质功能化和应用方法的新发展，更小的抗体衍生片段正成为人们关注的焦点。其中，源自骆驼的纳米体起着突出的作用。在大多数应用中，纳米体可以取代全尺寸抗体，并使传统抗体难以使用的新应用成为可能。在这里，我们回顾了纳米体的多用途性质，讨论了它们作为抗病毒治疗药物、诊断药物的前景，以及它们作为揭示病毒感染和疾病新方面的研究工具的适用性。

引用次数: 2

Disruption of the cGAS/STING axis does not impair sensing of MVA in BHK21 cells. cGAS/STING轴的破坏不影响BHK21细胞对MVA的感知。

The Journal of general virology

Pub Date : 2022-05-01 DOI: 10.1099/jgv.0.001755

A. Hood, Rebecca P. Sumner, C. Maluquer de Motes

Modified vaccinia Ankara (MVA) is an attenuated strain of vaccinia virus (VACV), a dsDNA virus that replicates its genome in the cytoplasm and as a result is canonically sensed by the cyclic GMP-AMP synthase (cGAS) and its downstream stimulator of interferon genes (STING). MVA has a highly restricted host range due to major deletions in its genome including inactivation of immunomodulatory genes, only being able to grow in avian cells and the hamster cell line BHK21. Here we studied the interplay between MVA and the cGAS/STING DNA in this permissive cell line and determined whether manipulation of this axis could impact MVA replication and cell responses. We demonstrate that BHK21 cells retain a functional cGAS/STING axis that responds to canonical DNA sensing agonists, upregulating interferon stimulated genes (ISGs). BHK21 cells also respond to MVA, but with a distinct ISG profile. This profile remains unaltered after CRISPR/Cas9 knock-out editing of STING and ablation of cytosolic DNA responses, indicating that MVA responses are independent of the cGAS/STING axis. Furthermore, infection by MVA diminishes the ability of BHK21 cells to respond to exogenous DNA suggesting that MVA still encodes uncharacterised inhibitors of DNA sensing. This suggests that using attenuated strains in permissive cell lines may assist in identification of novel host-virus interactions that may be of relevance to disease or the therapeutic applications of poxviruses.

修饰安卡拉牛痘(MVA)是牛痘病毒(VACV)的减毒株，它是一种dsDNA病毒，在细胞质中复制其基因组，因此通常被环GMP-AMP合成酶(cGAS)及其下游干扰素基因刺激因子(STING)感知。由于MVA基因组的主要缺失(包括免疫调节基因失活)，其宿主范围受到高度限制，仅能在禽类细胞和仓鼠细胞系BHK21中生长。在这里，我们研究了MVA和cGAS/STING DNA之间的相互作用，并确定操纵该轴是否会影响MVA复制和细胞反应。我们证明BHK21细胞保留了一个功能性的cGAS/STING轴，该轴响应典型的DNA传感激动剂，上调干扰素刺激基因(ISGs)。BHK21细胞也对MVA有反应，但具有不同的ISG特征。在CRISPR/Cas9敲除STING和消融细胞质DNA应答后，这一图谱保持不变，表明MVA应答独立于cGAS/STING轴。此外，MVA感染降低了BHK21细胞对外源DNA的反应能力，这表明MVA仍然编码未表征的DNA感应抑制剂。这表明，在允许细胞系中使用减毒株可能有助于鉴定可能与疾病或痘病毒治疗应用相关的新型宿主-病毒相互作用。

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引用次数: 1

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