Virologica Sinica最新文献

英文中文

Bibliometric analysis of virology advancements in the 21st century 21 世纪病毒学进展的文献计量分析。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-12-01 DOI: 10.1016/j.virs.2024.08.009

Lili Ma , Wei Pan , Jiali Si

引用次数: 0

Identification of mutations in viral proteins involved in cell adaptation using a reverse genetic system of the live attenuated hepatitis A virus vaccine H2 strain 利用甲型肝炎病毒减毒活疫苗 H2 株的反向遗传系统鉴定参与细胞适应的病毒蛋白变异。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-12-01 DOI: 10.1016/j.virs.2024.08.004

Xiu-Li Yan , Jian Li , Qing-Qing Ma , Hong-Jiang Wang , Lin Li , Hui Zhao , Cheng-Feng Qin , Xiao-Feng Li

The live attenuated hepatitis A virus vaccine H2 strain was developed by passaging a wild-type H2w isolate in cell cultures. Currently, the mechanism underlying its attenuation phenotype remain largely unknown. In this study, we generated a full-length infectious cDNA clone of the H2 strain using in-fusion techniques. The recovered H2 strain (H2ic) from the cDNA clone exhibited an efficient replication in both the hepatoma cell line Huh7.5.1 and the 2BS cell line used for vaccine production, similar to the parental H2 strain. Additionally, H2ic did not cause disease in Ifnar1^−/− C57 mice, consistent with the H2 strain. To explore the cell-adaptive mutations of the H2 strain, chimeric viruses were generated by replacing its non-structural proteins with corresponding regions from H2w using the infectious cDNA clone as a genetic backbone. The chimeric viruses carrying the 3C or 3D proteins from H2w showed decreased replication in Huh7.5.1 and 2BS cell lines compared to H2ic. Other chimeric viruses containing the 2B, 2C, or 3A proteins from H2w failed to be recovered. Furthermore, there were no significant differences in disease manifestation in mice between H2ic and the recovered chimeric viruses. These results demonstrate that adaptive mutations in the 2B, 2C, and 3A proteins are essential for efficient replication of the H2 strain in cell cultures. Mutations in the 3C and 3D proteins contribute to enhanced replication in cell cultures but did not influence the attenuated phenotypes in mice. Together, this study presents the first reverse genetic system of the H2 strain and identifies viral proteins essential for adaptation to cell cultures.

甲型肝炎病毒减毒活疫苗 H2 株是通过将野生型 H2w 分离物在细胞培养物中传代培养出来的。目前，其减毒表型的基本机制仍不清楚。在本研究中，我们利用内融合技术生成了 H2 株的全长感染性 cDNA 克隆。从该 cDNA 克隆中回收的 H2 株（H2ic）在肝癌细胞系 Huh7.5.1 和用于生产疫苗的 2BS 细胞系中均表现出高效复制，与亲本 H2 株相似。此外，H2ic 在 Ifnar1-/- C57 小鼠中不会致病，这与 H2 株一致。为了探索 H2 株的细胞适应性突变，我们以感染性 cDNA 克隆为基因骨架，用 H2w 的相应区域取代其非结构蛋白，生成了嵌合病毒。与 H2ic 相比，携带 H2w 的 3C 或 3D 蛋白的嵌合病毒在 Huh7.5.1 和 2BS 细胞系中的复制能力下降。其他含有 H2w 的 2B、2C 或 3A 蛋白的嵌合病毒则未能恢复。此外，H2ic 和回收的嵌合病毒在小鼠的疾病表现上没有明显差异。这些结果表明，2B、2C 和 3A 蛋白的适应性突变对于 H2 株在细胞培养物中的有效复制至关重要。3C和3D蛋白的突变有助于增强细胞培养物中的复制，但并不影响小鼠体内的减弱表型。总之，这项研究首次提出了 H2 株的反向遗传系统，并确定了适应细胞培养所必需的病毒蛋白。

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引用次数: 0

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IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-12-01 DOI: 10.1016/S1995-820X(24)00187-1

引用次数: 0

Ten computational challenges in human virome studies 人类病毒组研究中的十大计算挑战。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-12-01 DOI: 10.1016/j.virs.2024.04.008

Yifan Wu, Yousong Peng

In recent years, substantial advancements have been achieved in understanding the diversity of the human virome and its intricate roles in human health and diseases. Despite this progress, the field of human virome research remains nascent, primarily hindered by the lack of effective methods, particularly in the domain of computational tools. This perspective systematically outlines ten computational challenges spanning various types of virome studies. These challenges arise due to the vast diversity of viromes, the absence of a universal marker gene in viral genomes, the low abundance of virus populations, the remote or minimal homology of viral proteins to known proteins, and the highly dynamic and heterogeneous nature of viromes. For each computational challenge, we discuss the underlying reasons, current research progress, and potential solutions. The resolution of these challenges necessitates ongoing collaboration among computational scientists, virologists, and multidisciplinary experts. In essence, this perspective serves as a comprehensive guide for directing computational efforts in human virome studies.

近年来，人们在了解人类病毒组的多样性及其在人类健康和疾病中的复杂作用方面取得了长足的进步。尽管取得了这些进展，人类病毒组研究领域仍处于起步阶段，主要原因是缺乏有效的方法，特别是在计算工具领域。本视角系统地概述了各种类型病毒组研究面临的十大计算挑战。出现这些挑战的原因包括：病毒体种类繁多、病毒基因组中缺乏通用标记基因、病毒种群丰度低、病毒蛋白与已知蛋白同源性低或同源性极低，以及病毒体的高度动态性和异质性。对于每项计算挑战，我们都会讨论其背后的原因、当前的研究进展以及潜在的解决方案。这些挑战的解决需要计算科学家、病毒学家和多学科专家之间的持续合作。从本质上讲，这一观点是指导人类病毒组研究中计算工作的综合指南。

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引用次数: 0

The first discovery of severe fever with thrombocytopenia virus in the center of metropolitan Beijing, China 在中国北京市中心首次发现严重发热伴血小板减少病毒。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-12-01 DOI: 10.1016/j.virs.2024.11.002

Fei Yuan , Lianglong Zhu , Di Tian , Mengyu Xia , Ming-hao Zheng , Qing Zhang , Tingyu Zhang , Xing Zhang , Aihua Zheng

Severe fever with thrombocytopenia virus (SFTSV), an emerging tick-borne bandavirus, poses a significant public health threat in rural China. Since 2021, an increase of local cases has been noted in the rural-urban fringe of Beijing. This study aimed to assess the formation of natural foci in urban areas by conducting a field survey of ticks and hedgehogs from the second to fifth ring roads of Beijing. Our survey revealed a diverse tick population in city parks, including the major SFTSV vector, Haemaphysalis longicornis. Parthenogenetic H. longicornis, known for its role in the rapid spread of SFTSV, was identified in key locations such as Beihai Park and Taoranting Park, near the Forbidden City. Notably, high SFTSV seroprevalence and RNA prevalence were found in hedgehogs and parasitic ticks in the center of Beijing. Phylogenetic analyses of SFTSV RNA and mitochondrial sequences of parthenogenetic H. longicornis ticks revealed the existence of diverse lineages of SFTSV and H. longicornis ticks within Beijing, suggesting multiple invasion events happened. These findings reveal the circulation of SFTSV in central Beijing, highlighting the need for urgent attention and enhanced surveillance measures.

严重发热伴血小板减少病毒（SFTSV）是一种新出现的蜱媒带状病毒，对中国农村地区的公共卫生构成严重威胁。自2021年以来，北京城乡结合部的本地病例有所增加。本研究旨在通过对北京二环至五环的蜱虫和刺猬进行实地调查，评估城市地区自然病灶的形成情况。我们的调查显示，城市公园中的蜱虫种群多种多样，其中包括主要的SFTSV病媒长角蜱。在故宫附近的北海公园和陶然亭公园等重要地点发现了孤雌生殖的长角蜱，它因在SFTSV的快速传播中扮演重要角色而闻名。值得注意的是，在北京市中心的刺猬和寄生蜱中发现了较高的 SFTSV 血清流行率和 RNA 流行率。通过对 SFTSV RNA 和孤雌生殖的长角蜱线粒体序列进行系统进化分析，发现北京地区存在 SFTSV 和长角蜱的不同系谱，表明发生过多次入侵事件。这些研究结果揭示了SFTSV在北京中心城区的流行情况，强调了采取紧急措施和加强监测的必要性。

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引用次数: 0

Efficient and robust reverse genetics system for bovine rotavirus generation and its application for antiviral screening 用于生成牛轮状病毒的高效、稳健的反向遗传学系统及其在抗病毒筛选中的应用。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-12-01 DOI: 10.1016/j.virs.2024.09.010

Song-Kang Qin , Kuan-Hao Li , Ben-Jin Liu , Cun Cao , De-Bin Yu , Zhi-Gang Jiang , Jun Wang , Yu-Xin Han , Fang Wang , Ying-Lin Qi , Chao Sun , Li Yu , Ji-Tao Chang , Xin Yin

Unveiling the molecular mechanisms underlying rotavirus replication and pathogenesis has been hampered by the lack of a reverse genetics (RG) system in the past. Since 2017, multiple plasmid-based RG systems for simian, human, and murine-like rotaviruses have been established. However, none of the described methods have supported the recovery of bovine rotaviruses (BRVs). Here, we established an optimized plasmid-based RG system for BRV culture-adapted strain (BRV G10P [15] BLR) and clinical isolates (BRV G6P [1] C73, G10P [11] HM26) based on a BHK-T7 cell clone stably expressing T7 polymerase. Furthermore, using this optimized RG system, we successfully rescued the reporter virus BRV rC73/Zs, rHM26/Zs and rBLR/Zs, harboring a genetically modified 1.8-kb segment 7 encoding full-length nonstructural protein 3 (NSP3) fused to ZsGreen, a 232-amino acid green fluorescent protein. Analysis of the stability of genomic insertions showed that the rC73/Zs and rBLR/Zs replicated efficiently and were genetically stable in seven rounds of serial passaging, while rHM26/Zs can be stabilized only up to the third generation, indicating that the BRV segment composition may influence the viral fitness. In addition, we adopted the recombinant reporter viruses for high-throughput screening application and discovered 12 candidates out of 1440 compounds with potential antiviral activities against rotavirus. In summary, this improved RG system of BRVs represents an important tool with great potential for understanding the molecular biology of BRV and facilitates the development of novel therapeutics and vaccines for BRV.

由于过去缺乏反向遗传学（RG）系统，揭示轮状病毒复制和致病的分子机制一直受到阻碍。自 2017 年以来，针对猿、人和类鼠轮状病毒建立了多种基于质粒的 RG 系统。然而，所描述的方法都不支持牛轮状病毒（BRV）的回收。在此，我们以稳定表达 T7 聚合酶的 BHK-T7 细胞克隆为基础，针对 BRV 培养适应株（BRV G10P [15] BLR）和临床分离株（BRV G6P[1] C73、G10P[11] HM26）建立了基于质粒的优化 RG 系统。此外，利用这种优化的 RG 系统，我们成功地解救了报告病毒 BRV rC73/Zs、rHM26/Zs 和 rBLR/Zs，它们都含有经过基因修饰的 1.8-kb 片段 7，编码全长的非结构蛋白 3（NSP3），并与 ZsGreen（一种 232 氨基酸的绿色荧光蛋白）融合。对插入基因组稳定性的分析表明，rC73/Zs和rBLR/Zs能高效复制，并在七轮连续传代中保持基因稳定，而rHM26/Zs只能稳定到第三代，这表明BRV片段的组成可能会影响病毒的适应性。此外，我们还将重组报告病毒用于高通量筛选，从 1440 个化合物中发现了 12 个具有潜在抗轮状病毒活性的候选化合物。总之，这种改进的 BRV RG 系统是了解 BRV 分子生物学的重要工具，具有巨大的潜力，有助于开发 BRV 新型疗法和疫苗。

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引用次数: 0

2024 Reviewer Acknowledgment

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-12-01 DOI: 10.1016/S1995-820X(24)00202-5

引用次数: 0

Bis-benzylisoquinoline alkaloids inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy 双苄基异喹啉生物碱通过影响内溶酶体转运和自噬抑制黄病毒的进入和复制。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-12-01 DOI: 10.1016/j.virs.2024.09.001

Lihong Huang , Lele Liu , Junhai Zhu , Nanjun Chen , Jie Chen , Chuen-Fuk Chan , Fei Gao , Youqin Yin , Jiufeng Sun , Rongxin Zhang , Kehui Zhang , Wenbao Qi , Jianbo Yue

Flaviviruses, such as dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV), represent a substantial public health challenge as there are currently no approved treatments available. Here, we investigated the antiviral effects of bis-benzylisoquinoline alkaloids (BBAs) on flavivirus infections. We evaluated five specific BBAs—berbamine, tetrandrine, iso-tetrandrine, fangchinoline, and cepharanthine—and found that they effectively inhibited infections by ZIKV, DENV, or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle. Furthermore, we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes, causing lysosomal pH alkalization. Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels, leading to lysosomal dysfunction and reducing the expression of NCAM1, a key receptor for the entry of ZIKV into cells, thereby decreasing cells susceptibility to ZIKV infection. Additionally, BBAs inhibited the fusion of autophagosomes and lysosomes, significantly reducing viral RNA replication. Collectively, our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy, respectively, underscoring the potential of BBAs as therapeutic agents against flavivirus infections.

登革病毒（DENV）、寨卡病毒（ZIKV）和日本脑炎病毒（JEV）等黄病毒是公共卫生面临的重大挑战，因为目前还没有获得批准的治疗方法。在这里，我们研究了双苄基异喹啉生物碱（BBAs）对黄病毒感染的抗病毒作用。我们评估了五种特定的 BBA--小檗胺、四氢喹啉、异四氢喹啉、芳喹啉和头花苋碱--发现它们通过阻断黄病毒生命周期中病毒进入和基因组复制阶段，有效抑制了 ZIKV、DENV 或 JEV 的感染。此外，我们还合成了一种含荧光团的 BBA，结果表明 BBA 可靶向内溶酶体，使溶酶体 pH 碱化。对 BBAs 抑制 ZIKV 感染的机理研究发现，这些化合物阻断了 TRPML 通道，导致溶酶体功能紊乱，减少了 ZIKV 进入细胞的关键受体 NCAM1 的表达，从而降低了细胞对 ZIKV 感染的易感性。此外，BBAs 还能抑制自噬体和溶酶体的融合，从而显著减少病毒 RNA 的复制。总之，我们的研究结果表明，BBAs 可分别通过损害溶酶体内转运和自噬作用来抑制黄病毒的进入和复制，突出了 BBAs 作为黄病毒感染治疗剂的潜力。

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引用次数: 0

A G3P[3] bat rotavirus can infect cultured human cholangiocytes and cause biliary atresia symptom in suckling mice G3P[3]蝙蝠轮状病毒可感染培养的人类胆管细胞，并导致乳鼠出现胆道闭锁症状。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-12-01 DOI: 10.1016/j.virs.2024.09.009

Pengfei Hao , Zhaoxia Pang , Qiaoqiao Qu , Chunmei Cui , Yuhang Jiang , Jing Chen , Zihan Gao , Zhiqiang Xu , Letian Li , Ningyi Jin , Chang Li

引用次数: 0

Generation and characterization of a novel ovariole cell line derived from Spodoptera frugiperda in China with sensitivity to both SfMNPV and AcMNPV 产生并鉴定对 SfMNPV 和 AcMNPV 均敏感的新型卵巢细胞系。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-12-01 DOI: 10.1016/j.virs.2024.10.002

Yan Tong , Wenyi Jin , Xuan Li , Lin Guo , Gang Luo , Qian Meng , Jihong Zhang , Qilian Qin , Huan Zhang

Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV), belonging to the species Alphabaculovirus spofrugiperdae, has been recently registered as an insecticide in China. This virus has a specific effect on the global major agricultural pest Spodoptera frugiperda. To gain insights into viral infection, replication processes, and the complex formation of viral particles, in vitro studies using cell lines are essential tools. Although the IPLB-Sf9 and IPLB-Sf21 cell lines derived from S. frugiperda are widely used for studies on the infection and replication mechanisms of Autographa californica multiple nucleopolyhedrovirus (AcMNPV), their capacity to produce viral polyhedra after SfMNPV infection is not optimal. To address this limitation, a novel cell line named IOZCAS-Sf-1 was developed from a S. frugiperda population in Yunnan, China. The mitochondrial COX1 gene analysis confirmed the species origin of the IOZCAS-Sf-1 cell line. Furthermore, a comparative study was carried out to contrast the COX1 gene sequence of this novel cell line with that of IPLB-Sf9, highlighting the distinctions between the two. Importantly, the IOZCAS-Sf-1 cells exhibited a remarkable ability to generate polyhedra when infected with AcMNPV and SfMNPV, respectively. Consequently, this cellular lineage is considered a promising and valuable resource. It serves not only to investigate the molecular mechanisms of viral replication and its impact on host cells, but also to explore the transfection efficiency of SfMNPV DNA. This exploration further expands into its potential application in recombinant DNA experiments, laying a theoretical groundwork for the advancement of more effective biopesticides and sustainable agricultural practices.

鞘翅目多核多角体病毒（Spodoptera frugiperda multiple nucleopolyhedrovirus，SfMNPV）属于鞘翅目多核多角体病毒（Alphabaculovirus spofrugiperdae），最近已在中国登记为杀虫剂。该病毒对全球主要农业害虫鞘翅目蚜虫（Spodoptera frugiperda）具有特异性作用。要深入了解病毒感染、复制过程以及病毒颗粒的复杂形成，使用细胞系进行体外研究是必不可少的工具。虽然源自鞘翅目蚜虫的 IPLB-Sf9 和 IPLB-Sf21 细胞系被广泛用于研究加州伯劳多核多面体病毒（AcMNPV）的感染和复制机制，但它们在 SfMNPV 感染后产生病毒多面体的能力并不理想。为了解决这个问题，我们从中国云南的俭蝽种群中培育出了一种名为 IOZCAS-Sf-1 的新型细胞系。线粒体 COX1 基因分析证实了 IOZCAS-Sf-1 细胞系的物种来源。此外，还进行了一项比较研究，将这一新型细胞系的 COX1 基因序列与 IPLB-Sf9 的 COX1 基因序列进行了对比，突出了两者之间的区别。重要的是，IOZCAS-Sf-1 细胞在分别感染 AcMNPV 和 SfMNPV 后，都表现出了生成多面体的显著能力。因此，这一细胞系被认为是一种有前途的宝贵资源。它不仅可用于研究病毒复制的分子机制及其对宿主细胞的影响，还可用于探索 SfMNPV DNA 的转染效率。这一探索进一步拓展了其在 DNA 重组实验中的潜在应用，为开发更有效的生物农药和可持续农业实践奠定了理论基础。

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