Virologica Sinica最新文献_第5页

Virome-wide analysis of histone modification mimicry motifs carried by viral proteins 对病毒蛋白所携带的组蛋白修饰模拟图案进行全病毒组分析。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.09.004

Yang Xiao , Shuofeng Yuan , Ye Qiu , Xing-Yi Ge

Histone mimicry (HM) refers to the presence of short linear motifs in viral proteins that mimic critical regions of host histone proteins. These motifs have the potential to interfere with host cell epigenome and counteract antiviral response. Recent research shows that HM is critical for the pathogenesis and transmissibility of influenza virus and coronavirus. However, the distribution, characteristics, and functions of HM in eukaryotic viruses remain obscure. Herein, we developed a bioinformatic pipeline, Histone Motif Scan (HiScan), to identify HM motifs in viral proteins and predict their functions in silico. By analyzing 592,643 viral proteins using HiScan, we found that putative HM motifs were widely distributed in most viral proteins. Among animal viruses, the ratio of HM motifs between DNA viruses and RNA viruses was approximately 1.9:1, and viruses with smaller genomes had a higher density of HM motifs. Notably, coronaviruses exhibited an uneven distribution of HM motifs, with betacoronaviruses (including most human pathogenic coronaviruses) harboring more HM motifs than other coronaviruses, primarily in the NSP3, S, and N proteins. In summary, our virome-wide screening of HM motifs using HiScan revealed extensive but uneven distribution of HM motifs in most viral proteins, with a preference in DNA viruses. Viral HM may play an important role in modulating viral pathogenicity and virus-host interactions, making it an attractive area of research in virology and antiviral medication.

组蛋白模拟（HM）是指病毒蛋白中存在短的线性基团，这些基团模仿宿主组蛋白的关键区域。这些基团有可能干扰宿主细胞表观基因组并抵消抗病毒反应。最新研究表明，HM 对流感病毒和冠状病毒的致病和传播至关重要。然而，HM 在真核病毒中的分布、特征和功能仍不清楚。在此，我们开发了一种生物信息学管道--组蛋白基序扫描（HiScan），用于识别病毒蛋白中的HM基序并在硅学中预测其功能。通过使用HiScan分析592,643个病毒蛋白，我们发现假定的HM基团广泛分布于大多数病毒蛋白中。在动物病毒中，DNA病毒和RNA病毒的HM基序比例约为1.9:1，基因组较小的病毒HM基序密度更高。值得注意的是，冠状病毒的HM基序分布不均，β-冠状病毒（包括大多数人类致病性冠状病毒）比其他冠状病毒含有更多的HM基序，主要分布在NSP3、S和N蛋白中。总之，我们利用 HiScan 对病毒体范围内的 HM 基序进行了筛选，发现 HM 基序在大多数病毒蛋白中的分布广泛但不均衡，DNA 病毒更偏爱 HM 基序。病毒 HM 可能在调节病毒致病性和病毒-宿主相互作用方面发挥重要作用，因此是病毒学和抗病毒药物研究中一个具有吸引力的领域。

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引用次数: 0

Rapid diagnosis of a fox's death case using nanopore sequencing reveals the infection with an Artic-like rabies virus 利用纳米孔测序技术对狐狸死亡病例进行快速诊断，发现感染了一种类似北极的狂犬病毒。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.010

Yuhang Liu , Zhiqiang Liu , Jian Li , Xiaomin Yan , Weidi Xu , Le Yi , Changchun Tu , Biao He

引用次数: 0

A novel vesicular stomatitis virus armed with IL-2 mimic for oncolytic therapy 用于溶瘤疗法的新型水泡性口炎病毒与 IL-2 模拟物。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.09.007

Manman Wu , Yiwei Wang , Chuanjian Wu , Huang Huang , Xinyuan Zhou , Jun Wang , Sidong Xiong , Chunsheng Dong

Oncolytic virus (OV) is increasingly being recognized as a novel vector in cancer immunotherapy. Increasing evidence suggests that OV has the ability to change the immune status of tumor microenvironment, so called transformation of ‘cold’ tumors into ‘hot’ tumors. The improved anti-tumor immunity can be induced by OV and further enhanced through the combination of various immunomodulators. The Neo-2/15 is a newly de novo synthesized cytokine that functions as both IL-2 and IL-15. However, it specifically lacks the binding site of IL-2 receptor α subunit (CD25), therefore unable to induce the Treg proliferation. In present study, a recombinant vesicular stomatitis virus expressing the Neo-2/15 (VSV^M51R-Neo-2/15) was generated. Intratumoral delivery of VSV^M51R-Neo-2/15 efficiently inhibited tumor growth in mice without causing the IL-2-related toxicity previously observed in clinic. Moreover, treatment with VSV^M51R-Neo-2/15 increased the number of activated CD8⁺ T cells but not Treg cells in tumors. More tumor-bearing mice were survival with VSV^M51R-Neo-2/15 treatment, and the surviving mice displayed enhanced protection against tumor cell rechallenge due to the induced anti-tumor immunity. In addition, combination therapy of OV and anti-PD-L1 immune checkpoint inhibitors further enhanced the anti-tumor immune response. These findings suggest that our novel VSV^M51R-Neo-2/15 can effectively inhibit the tumor growth and enhance the sensitivity to immune checkpoint inhibitors, providing promising attempts for further clinical trials.

人们越来越认识到，溶瘤病毒（OV）是癌症免疫疗法中的一种新型载体。越来越多的证据表明，OV 有能力改变肿瘤微环境的免疫状态，即所谓的将 "冷 "肿瘤转化为 "热 "肿瘤。OV 可以诱导抗肿瘤免疫力的提高，并通过联合使用各种免疫调节剂进一步增强抗肿瘤免疫力。Neo-2/15 是一种新合成的细胞因子，同时具有 IL-2 和 IL-15 的功能。然而，它特异性地缺乏IL-2受体α亚基（CD25）的结合位点，因此无法诱导Treg增殖。本研究生成了表达Neo-2/15的重组水泡性口炎病毒（VSVM51R-Neo-2/15）。VSVM51R-Neo-2/15的瘤内给药能有效抑制小鼠的肿瘤生长，而不会引起之前在临床上观察到的IL-2相关毒性。此外，VSVM51R-Neo-2/15 还能增加肿瘤中活化 CD8+ T 细胞的数量，但不能增加 Treg 细胞的数量。经 VSVM51R-Neo-2/15 治疗的肿瘤小鼠存活率更高，由于诱导了抗肿瘤免疫，存活小鼠对肿瘤细胞再挑战的保护能力增强。此外，OV和抗PD-L1免疫检查点抑制剂的联合治疗进一步增强了抗肿瘤免疫反应。这些研究结果表明，我们的新型VSVM51R-Neo-2/15能有效抑制肿瘤生长并提高对免疫检查点抑制剂的敏感性，为进一步的临床试验提供了有益的尝试。

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引用次数: 0

Identification of a novel caspase cleavage motif AEAD 鉴定新型 Caspase 裂解基序 AEAD。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.001

Yujie Fang , Zhou Gong , Miaomiao You , Ke Peng

Infections of many viruses induce caspase activation to regulate multiple cellular pathways, including programmed cell death, immune signaling and etc. Characterizations of caspase cleavage sites and substrates are important for understanding the regulation mechanisms of caspase activation. Here, we identified and analyzed a novel caspase cleavage motif AEAD, and confirmed its caspase dependent cleavage activity in natural substrate, such as nitric oxide-associated protein 1 (NOA1). Fusing the enhanced green fluorescent protein (EGFP) with the mitochondrial marker protein Tom20 through the AEAD motif peptide localized EGFP to the mitochondria. Upon the activation of caspase triggered by Sendai virus (SeV) or herpes simplex virus type 1 (HSV-1) infection, EGFP diffusely localized to the cell due to the caspase-mediated cleavage, thus allowing visual detection of the virus-induced caspase activation. An AEAD peptide-derived inhibitor Z-AEAD-FMK were developed, which significantly inhibited the activities of caspases-1, -3, -6, -7, -8 and -9, exhibiting a broad caspase inhibition effect. The inhibitor further prevented caspases-mediated cleavage of downstream substrates, including BID, PARP1, LMNA, pro-IL-1β, pro-IL-18, GSDMD and GSDME, protecting cells from virus-induced apoptotic and pyroptotic cell death. Together, our findings provide a new perspective for the identification of novel caspase cleavage motifs and the development of new caspase inhibitors and anti-inflammatory drugs.

许多病毒感染会诱导caspase活化，从而调控多种细胞通路，包括程序性细胞死亡、免疫信号转导等。鉴定 caspase 的裂解位点和底物对于了解 caspase 激活的调控机制非常重要。在这里，我们发现并分析了一种新型的caspase裂解基序AEAD，并证实了它在一氧化氮相关蛋白1（NOA1）等天然底物中的依赖性裂解活性。将增强型绿色荧光蛋白（EGFP）与线粒体标记蛋白 Tom20 通过 AEAD 基序肽结合，可将 EGFP 定位于线粒体。当仙台病毒（SeV）或 1 型单纯疱疹病毒（HSV-1）感染引发树突酶活化时，由于树突酶介导的裂解，EGFP 在细胞内弥漫定位，因此可以直观地检测病毒诱导的树突酶活化。研究人员开发了一种由 AEAD 肽衍生的抑制剂 Z-AEAD-FMK，它能显著抑制 caspase-1、-3、-6、-7、-8 和-9 的活性，表现出广泛的 caspase 抑制作用。该抑制剂还能进一步阻止 Caspases 介导的下游底物（包括 BID、PARP1、LMNA、pro-IL-1β、pro-IL-18、GSDMD 和 GSDME）的裂解，从而保护细胞免受病毒诱导的细胞凋亡和猝死。总之，我们的研究结果为鉴定新型树突酶裂解基团、开发新型树突酶抑制剂和抗炎药物提供了新的视角。

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引用次数: 0

The spatiotemporal analysis of SARS-CoV-2 transmission in China since the termination of the dynamic zero-COVID policy 自动态零COVID政策终止以来中国SARS-CoV-2传播的时空分析。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.09.003

Jiaying Li , Jingqi Yang , Xiao Ding , Hangyu Zhou , Na Han , Aiping Wu

China's dynamic zero-COVID policy has effectively curbed the spread of SARS-CoV-2, while inadvertently creating immunity gaps within its population. Subsequent surges in COVID-19 cases linked to various SARS-CoV-2 lineages post-policy termination necessitate a thorough investigation into the epidemiological landscape. This study addresses this issue by analyzing a comprehensive dataset of 39,456 high-quality genomes collected nationwide over an 11-month period since policy termination. Through lineage assignment, phylogenetic analysis, pandemic pattern comparison, phylodynamic reconstruction, and recombination detection, we found that China's post-epidemic period could be divided into three stages, along with dynamic changes in dominant lineages. Geographical clustering of similar lineages implies the importance of cross-border cooperation among neighboring regions. Compared to the USA, UK, and Japan, China exhibits unique trajectories of lineage epidemics, characterized by initial lagging followed by subsequent advancement, indicating the potential influence of diverse prevention and control policies on lineage epidemic patterns. Hong Kong, Shanghai, and Hubei emerge as pivotal nodes in the nationwide spread, marking a shift in the transmission center from east to central regions of China. Although China hasn't experienced significant variant emergence, the detection and validation of the novel recombination event, XCN lineage, underscore the ongoing virus evolution. Overall, this study systematically analyzes the spatiotemporal transmission of SARS-CoV-2 virus in China since the termination of the dynamic zero-COVID policy, offering valuable insights for regional surveillance and evidence-based public health policymaking.

中国动态的零 COVID 政策在有效遏制 SARS-CoV-2 传播的同时，也无意中在人群中造成了免疫空白。政策终止后，与各种 SARS-CoV-2 株系相关的 COVID-19 病例随之激增，因此有必要对流行病学状况进行彻底调查。本研究通过分析政策终止后 11 个月期间在全国范围内收集的 39,456 个高质量基因组的综合数据集来解决这一问题。通过系谱分配、系统发育分析、大流行模式比较、系统动力学重建和重组检测，我们发现中国的疫情后时期可分为三个阶段，并伴随着优势系谱的动态变化。相似品系的地理聚集意味着相邻地区之间跨境合作的重要性。与美国、英国和日本相比，中国表现出独特的世系流行轨迹，其特点是最初滞后，随后推进，这表明多样化的防控政策对世系流行模式具有潜在影响。香港、上海和湖北成为全国传播的关键节点，标志着传播中心从中国东部地区向中部地区转移。虽然中国尚未出现重大变异，但新型重组事件--XCN系的检测和验证凸显了病毒的持续进化。总之，本研究系统地分析了自动态零COVID政策终止以来中国SARS-CoV-2病毒的时空传播情况，为区域监测和循证公共卫生决策提供了有价值的见解。

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引用次数: 0

The unique immune evasion mechanisms of the mpox virus and their implication for developing new vaccines and immunotherapies Mpox 病毒独特的免疫规避机制及其对开发新型疫苗和免疫疗法的影响。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.008

Dong Fang , Yan Liu , Dou Dou , Bin Su

Mpox is an infectious and contagious zoonotic disease caused by the mpox virus (MPXV), which belongs to the genus Orthopoxvirus. Since 2022, MPXV has posed a significant threat to global public health. The emergence of thousands of cases across the Western Hemisphere prompted the World Health Organization to declare an emergency. The extensive coevolutionary history of poxviruses with humans has enabled these viruses to develop sophisticated mechanisms to counter the human immune system. Specifically, MPXV employs unique immune evasion strategies against a wide range of immunological elements, presenting a considerable challenge for treatment, especially following the discontinuation of routine smallpox vaccination among the general population. In this review, we start by discussing the entry of the mpox virus and the onset of early infection, followed by an introduction to the mechanisms by which the mpox virus can evade the innate and adaptive immune responses. Two caspase-1 inhibitory proteins and a PKR escape-related protein have been identified as phylogenomic hubs involved in modulating the immune environment during the MPXV infection. With respect to adaptive immunity, mpox viruses exhibit unique and exceptional T-cell inhibition capabilities, thereby comprehensively remodeling the host immune environment. The viral envelope also poses challenges for the neutralizing effects of antibodies and the complement system. The unique immune evasion mechanisms employed by MPXV make novel multi-epitope and nucleic acid-based vaccines highly promising research directions worth investigating. Finally, we briefly discuss the impact of MPXV infection on immunosuppressed patients and the current status of MPXV vaccine development. This review may provide valuable information for the development of new immunological treatments for mpox.

痘疹是一种由痘病毒（MPXV）引起的人畜共患传染性疾病，MPXV 属于正痘病毒属。自 2022 年以来，MPXV 已对全球公共卫生构成重大威胁。西半球出现的数千例病例促使世界卫生组织宣布进入紧急状态。痘病毒与人类广泛的共同进化史使这些病毒发展出了对抗人类免疫系统的复杂机制。具体来说，MPXV 采用了独特的免疫逃避策略来对抗各种免疫元素，这给治疗带来了巨大挑战，尤其是在普通人群停止常规天花疫苗接种之后。在这篇综述中，我们首先讨论了天花病毒的进入和早期感染的发生，然后介绍了天花病毒逃避先天性和适应性免疫反应的机制。两种 caspase-1 抑制蛋白和一种 PKR 逃逸相关蛋白已被确定为在 mpox 病毒感染期间参与调节免疫环境的系统基因组中心。在适应性免疫方面，mpox 病毒表现出独特的T细胞抑制能力，从而全面重塑了宿主的免疫环境。病毒包膜也给抗体和补体系统的中和作用带来了挑战。MPXV 所采用的独特免疫逃避机制使新型多表位疫苗和基于核酸的疫苗成为极具潜力的研究方向，值得我们深入研究。最后，我们简要讨论了 MPXV 感染对免疫抑制患者的影响以及 MPXV 疫苗的研发现状。本综述可为开发新的 mpox 免疫疗法提供有价值的信息。

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引用次数: 0

Trivalent SARS-CoV-2 virus-like particle vaccines exhibit broad-spectrum neutralization and protection against XBB.1 and BA.2.86 variants 三价 SARS-CoV-2 病毒样颗粒疫苗对 XBB.1 和 BA.2.86 变体具有广谱中和和保护作用。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.005

Lu Zhang , Siyu Tian , Jun Dai , Yuanyuan Li , Yu Zhou , Yan Li , Jiao Xu , Shuyun Liu , Zhiwei Lin , Zhaoyong Zhang , Jiantao Chen , Peilan Wei , Jingxian Zhao , Jing Jin , Yanqun Wang , Jincun Zhao

引用次数: 0

Antiviral activity of vitamin D derivatives against severe fever with thrombocytopenia syndrome virus in vitro and in vivo 维生素 D 衍生物在体外和体内对严重发热伴血小板减少综合征病毒的抗病毒活性。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.007

Chongda Luo , Xintong Yan , Shaokang Yang , Sichen Ren , Yan Luo , Jiazheng Li , Ping Wang , Yunfeng Shao , Wei Li , Song Li , Jingjing Yang , Ruiyuan Cao , Wu Zhong

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus that causes the severe fever thrombocytopenia syndrome, which manifests as fever and haemorrhage, accompanied by severe neurological complications. To date, no specific antiviral drugs have been approved for this indication. Herein, we investigated whether vitamin D derivatives inhibit SFTSV both in vitro and in vivo. An in vitro study demonstrated that vitamin D derivatives significantly suppressed viral RNA replication, plaque formation, and protein expression in a dose-dependent manner. Subsequently, in vivo studies revealed that doxercalciferol and alfacalcidol were associated with increased survival and reduced viral RNA load in the blood. Time-of-addition assay suggested that vitamin D derivatives primarily acted during the post-entry phase of SFTSV infection. However, cytopathic effect protective activity was not observed in RIG-I immunodeficient cell line Huh7.5, and the administration of vitamin D derivatives did not improve the survival rates or reduce the blood viral loads in adult A129 mice. Further transcriptome exploration into the antiviral mechanism revealed that alfacalcidol stimulates host innate immunity to exert antiviral effects. To expand the application of vitamin D derivatives, in vitro and in vivo drug combination assays were performed, which highlighted the synergistic effects of vitamin D derivatives and T-705 on SFTSV. The combination of alfacalcidol and T-705 significantly enhanced the therapeutic effects in mice. This study highlights the potential of vitamin D derivatives against SFTSV and suggests that they may have synergistic effects with other compounds used in the treatment of SFTSV infection.

严重发热伴血小板减少综合征病毒（SFTSV）是一种蜱媒病毒，可导致严重发热血小板减少综合征，表现为发热和出血，并伴有严重的神经系统并发症。迄今为止，还没有特定的抗病毒药物被批准用于这一适应症。在此，我们研究了维生素 D 衍生物是否能在体外和体内抑制 SFTSV。体外研究表明，维生素 D 衍生物能以剂量依赖性方式显著抑制病毒 RNA 复制、斑块形成和蛋白表达。随后的体内研究显示，多钙化醇和阿法骨化醇可提高存活率并降低血液中的病毒 RNA 负荷。添加时间测定表明，维生素 D 衍生物主要在 SFTSV 感染的后进入阶段发挥作用。然而，在 RIG-I 免疫缺陷细胞系 Huh7.5 中并未观察到细胞病理效应保护活性，而且服用维生素 D 衍生物并未提高成年 A129 小鼠的存活率或降低其血液中的病毒载量。对抗病毒机制的进一步转录组研究发现，阿法骨化醇能刺激宿主先天性免疫，从而发挥抗病毒作用。为了扩大维生素 D 衍生物的应用范围，研究人员进行了体外和体内联合用药试验，结果显示维生素 D 衍生物和 T-705 对 SFTSV 有协同作用。阿法骨化醇和 T-705 的联合用药显著增强了对小鼠的治疗效果。这项研究凸显了维生素 D 衍生物抗 SFTSV 的潜力，并表明它们与其他用于治疗 SFTSV 感染的化合物可能具有协同作用。

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引用次数: 0

Single-cell RNA-sequencing reveals a profound immune cell response in human cytomegalovirus-infected humanized mice 单细胞 RNA 序列分析揭示了人巨细胞病毒感染人源化小鼠体内免疫细胞的深刻反应。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.006

An Wang , Xiao-Xu Zhu , Yuanyuan Bie , Bowen Zhang , Wenting Ji , Jing Lou , Muhan Huang , Xi Zhou , Yujie Ren

Human cytomegalovirus (HCMV) is a common herpesvirus that persistently infects a large portion of the world's population. Despite the robust host immune response, HCMV is able to replicate, evade host defenses, and establish latency throughout the lifespan by developing multiple immunomodulatory strategies, making the studies on the interaction between HCMV infection and host response particularly important. HCMV has a strict host specificity that specifically infects humans. Therefore, most of the in vivo researches of HCMV rely on clinical samples. Fortunately, the establishment of humanized mouse models allows for convenient in-lab animal experiments involving HCMV infection. Single-cell RNA sequencing enables the study of the relationship between viral and host gene expressions at the single-cell level within host cells. In this study, we assessed the gene expression alterations of PBMCs at the single-cell level within HCMV-infected humanized mice, which sheds light onto the virus-host interactions in the context of HCMV infection of humanized mice and provides a valuable dataset for the related researches.

人类巨细胞病毒（HCMV）是一种常见的疱疹病毒，可持续感染全球大部分人口。尽管宿主具有强大的免疫反应，但 HCMV 仍能复制、逃避宿主的防御，并通过开发多种免疫调节策略在整个生命周期内建立潜伏期，因此对 HCMV 感染与宿主反应之间相互作用的研究尤为重要。HCMV 有严格的宿主特异性，会专门感染人类。因此，对 HCMV 的体内研究大多依赖于临床样本。幸运的是，人源化小鼠模型的建立方便了涉及 HCMV 感染的实验室动物实验。单细胞 RNA 测序可在宿主细胞内的单细胞水平上研究病毒与宿主基因表达之间的关系。本研究在单细胞水平上评估了人源化小鼠感染 HCMV 后 PBMC 的基因表达变化，揭示了人源化小鼠感染 HCMV 时病毒与宿主之间的相互作用，为相关研究提供了宝贵的数据集。

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引用次数: 0

A bivalent Delta/BA.5 mRNA vaccine elicits broad immune responses against various lineages of SARS-CoV-2 including JN.1 二价 Delta/BA.5 mRNA 疫苗可针对包括 JN.1 在内的多种 SARS-CoV-2 株系引起广泛的免疫反应。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.003

Kangyin Li , Qi Liu , Yan Wu , Bihao Wu , Shaohong Chen , Xinghai Zhang , Xiaoying Jia , Rui Gong , Yucai Peng , Huajun Zhang , Sandra Chiu

引用次数: 0