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Single-cycle Rift Valley fever virus particles from stable replicon cells enable discovery of antiviral CNX-1351 for multiple RNA viruses 来自稳定复制子细胞的单循环裂谷热病毒颗粒使多种RNA病毒的抗病毒药物CNX-1351得以发现。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.06.009
Zhichao Gao , Hongyuan Guo , Ziqiao Wang , Pengcheng Wang , Xinran Sun , Shimei Zhang , Fei Feng , Chao Shan , Youhua Xie , Rong Zhang
Rift Valley fever virus (RVFV) is a high-containment pathogen that causes severe diseases in humans, with no approved therapeutics available. Its classification as a biosafety level 3 (BSL-3) agent has limited research and therapeutic development due to safety concerns. In this study, we developed a stable replicon cell line maintaining the replication of L and S genomic segments of RVFV. Single-cycle viral replicon particles (VRPs) could be efficiently packaged through trans-complementation of glycoproteins from different strains, recapitulating authentic viral entry and replication while minimizing biosafety risks. Using this system, we conducted high-throughput screening of a small-molecule compound library and identified CNX-1351 as an antiviral agent for multiple RNA viruses. Mechanistic studies revealed that CNX-1351 inhibits viral replication, potentially by targeting the PI3K-Akt signaling pathway. This single-cycle VRP system provides a valuable tool for studying RVFV biology, host interactions, antiviral and vaccine development under reduced biosafety constraints.
裂谷热病毒(RVFV)是一种高度遏制的病原体,可在人类中引起严重疾病,目前尚无批准的治疗方法。由于安全方面的考虑,它被列为生物安全3级(BSL-3)药物,限制了研究和治疗开发。在这项研究中,我们开发了一种稳定的复制子细胞系,维持RVFV L和S基因组片段的复制。单循环病毒复制子颗粒(VRPs)可以通过不同菌株的糖蛋白的反式互补有效地包装,再现真实的病毒进入和复制,同时最大限度地降低生物安全风险。利用该系统,我们对一个小分子化合物文库进行了高通量筛选,并鉴定出CNX-1351作为多种RNA病毒的抗病毒药物。机制研究表明,CNX-1351可能通过靶向PI3K-Akt信号通路抑制病毒复制。这种单循环VRP系统为研究RVFV生物学、宿主相互作用、在生物安全限制降低的情况下开发抗病毒药物和疫苗提供了有价值的工具。
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引用次数: 0
Isolation and identification of a newly discovered broad-spectrum Acinetobacter baumannii phage and therapeutic validation against pan-resistant Acinetobacter baumannii 新发现的广谱鲍曼不动杆菌噬菌体的分离鉴定及对泛耐药鲍曼不动杆菌的治疗效果验证。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.06.003
Miaomiao Lin , Lele Xiong , Wen Li , Lingyan Xiao , Wei Zhang , Xiaogui Zhao , Yishan Zheng
The treatment of Acinetobacter baumannii (A. baumannii) poses significant clinical challenges due to its multidrug/pan-drug resistance. In this study, we isolated a broad-spectrum lytic A. baumannii phage, named P425, from medical wastewater, targeting nine multidrug-resistant A. baumannii (MDRAB) with diverse capsular types. Biological characterization revealed that P425 maintains activity at pH range of 3–12 and temperature range of 4–50 ​°C. It resists UV irradiation for 20 ​minutes, and had an optimal multiplicity of infection (OMOI) is 0.00001. The adsorption kinetics showed that P425 achieves > 90% within 10 ​minutes of incubation, and the one-step growth curve indicated a 10-min latent period, with a burst size of 184 ​PFU/cell. The genome sequencing results indicated that it harbors a double-stranded DNA genome of 40,583 bp with a GC content of 39.39%. Intergenomic similarity analysis classified it as a novel species within the Friunavirus genus, while electron microscopy results showed that it belongs to the Podoviridae family. Notably, P425 exhibits potent 24-h in vitro inhibitory activity against MDRAB, and demonstrates synergistic effect at an MOI of 0.001 when combined with five classes of antibiotics targeting distinct antimicrobial mechanisms. Safety evaluations confirmed the absence of cytotoxicity, hemolytic activity, or systemic toxicity both in vitro and in vivo. In mouse infection models, P425 can significantly improve the survival rates of mice infected with Ab25 (ST1791/KL101). When co-administered with levofloxacin, it achieved 100% protection against mortality and promoted immune recovery. Collectively, P425 is a prospective lytic phage that could offer novel strategies for combating MDRAB infections.
鲍曼不动杆菌(鲍曼不动杆菌)的多药/泛药耐药给其治疗带来了重大的临床挑战。在这项研究中,我们从医疗废水中分离出一种广谱分解鲍曼尼a.b ummannii噬菌体,命名为P425,靶向9种具有不同荚膜类型的耐多药鲍曼尼a.b ummannii (MDRAB)。生物学特性表明,P425在pH值3 ~ 12、温度4 ~ 50℃范围内保持活性。抗紫外线照射20 min,最佳感染复数(MOI)为0.00001。吸附动力学表明,P425在10 min内达到> 90%,一步生长曲线显示潜伏期为10 min,爆发大小为184 PFU/细胞。基因组测序结果表明,该菌株含有40583 bp的双链DNA基因组,GC含量为39.39%。基因组间相似性分析将其归类为弗鲁纳病毒属的新种,而电子显微镜结果显示它属于足病毒科。值得注意的是,P425对MDRAB表现出强大的24小时体外抑制活性,并且当与五类针对不同抗菌机制的抗生素联合使用时,显示出协同效应,MOI为0.001。安全性评估证实在体内和体外均无细胞毒性、溶血活性或全身毒性。在小鼠感染模型中,P425能显著提高Ab25 (ST1791/KL101)感染小鼠的存活率。当与左氧氟沙星联合使用时,它可以达到100%的死亡率保护并促进免疫恢复。总的来说,P425是一种有前景的裂解噬菌体,可以为对抗MDRAB感染提供新的策略。
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引用次数: 0
Isolation and phylogenetic analysis of swinepox virus from pigs in China 中国猪源猪瘟病毒的分离及系统发育分析。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.006
Nan Cao , Yamei Li , Xiangmin Li , Ping Qian
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引用次数: 0
Epidemiological and genomic surveillance of influenza A virus (pdm09 H1N1 and H3N2) strains from 2017 to 2025 in Tianjin, China 2017 - 2025年天津市甲型流感病毒(pdm09 H1N1和H3N2)株流行病学和基因组监测
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.011
Mingkun Wu , Liru Guo , Mei Kong , Ming Zou , Xiaochang Liu , Xiaoyan Li
Influenza A virus (IAV) remains a global public health concern, causing influenza-like illness and severe respiratory tract infections. Two major subtypes, A/pdm09 H1N1 and A/H3N2, circulate globally, and their epidemics are influenced by multiple factors, especially during the COVID-19 pandemic. Based on data from the National Influenza Surveillance Program in China, we analyzed the epidemiological and genomic data in Tianjin collected from 2017 to 2025. A total of 77,473 throat swabs were collected, of which 9144 were IAV-positive. The A/pdm09 H1N1 and A/H3N2 lineages exhibited distinct epidemics across different influenza seasons, with a decline in cases observed during the COVID-19 pandemic. We sequenced the genomes of 128 A/pdm09 H1N1 and 113 A/H3N2 clinical isolates and characterized their temporal evolution and genetic diversity using time-scaled phylogenetic analysis. Additionally, we conducted a genetic risk evaluation of the hemagglutinin and neuraminidase segments, identifying key amino acid residues associated with viral adaptation, transmissibility, virulence, and drug resistance. Moreover, no antigenic variants were found in clinical isolates during the recent influenza seasons, though reduced sensitivity to oseltamivir and zanamivir was observed in individual strains. Our surveillance highlights the epidemiology and evolution of IAV before and after the COVID-19 pandemic in Tianjin.
甲型流感病毒(IAV)仍然是一个全球公共卫生问题,可引起流感样疾病和严重呼吸道感染。A/pdm09 H1N1和A/H3N2两种主要亚型在全球流行,其流行受多种因素影响,特别是在COVID-19大流行期间。基于中国国家流感监测项目的数据,我们分析了天津市2017 - 2025年的流行病学和基因组学数据。共收集了77473份咽拭子,其中9144份呈iav阳性。A/pdm09 H1N1和A/H3N2谱系在不同的流感季节表现出不同的流行趋势,在COVID-19大流行期间观察到病例数下降。我们对128株A/pdm09 H1N1和113株A/H3N2临床分离株进行了基因组测序,并利用时间尺度的系统发育分析对其时间进化和遗传多样性进行了表征。此外,我们对血凝素和神经氨酸酶片段进行了遗传风险评估,确定了与病毒适应性、传播性、毒力和耐药性相关的关键氨基酸残基。此外,在最近的流感季节,临床分离株中未发现抗原变异,尽管在个别菌株中观察到对奥司他韦和扎那米韦的敏感性降低。我们的监测重点关注天津市COVID-19大流行前后IAV的流行病学和演变。
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引用次数: 0
First isolation and genomic characterization of a novel inter-genotype recombinant feline calicivirus from domestic cats: Implications for viral evolution 首次从家猫中分离出一种新的跨基因型重组猫杯状病毒并进行基因组鉴定:对病毒进化的影响。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.06.005
Xiaomei Tan , Liangliang Lin , Qi Zhang , Na Li , Ningning Dong , Shishi Wang , Wenqi Zhu , Maoqing Luo , Shuaisai Pang , Yanzhao Xu , Guangqing Liu , Chunchun Meng
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引用次数: 0
Clinical outcomes after HBsAg clearance in chronic hepatitis B patients treated with Peg-IFN α: A study with an 11- to 173-month follow-up Peg-IFN α治疗慢性乙型肝炎患者HBsAg清除后的临床结果:一项随访11至173个月的研究
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.06.008
Wen Deng , Hongxiao Hao , Ziyu Zhang , Xinxin Li , Weihua Cao , Yaqin Zhang , Shiyu Wang , Zixuan Gao , Linmei Yao , Shuojie Wang , Xin Wei , Wei Yi , Linqing Zhao , Yao Xie , Minghui Li
To investigate the risk and influencing factors of long-term liver adverse events in chronic hepatitis B patients achieving hepatitis B surface antigen (HBsAg) clearance after pegylated interferon α (Peg-IFN α) treatment, a retrospective analysis was conducted on 456 patients at Beijing Ditan Hospital from 2008 to 2023 who achieved HBsAg clearance and discontinued Peg-IFN α treatment. The baseline was defined as the time of HBsAg clearance and treatment cessation. The endpoint was the first occurrence of liver adverse events (hepatocellular carcinoma or ascites) or last follow-up. Subsequently, we evaluated the incidence and risk factors of liver adverse events, along with changes in liver fibrosis, cirrhosis, and liver function indicators. During a median follow-up of 70 months, the incidence of liver adverse events was 2.30%, hepatocellular carcinoma 1.76%, and ascites 0.55%. Older age and cirrhosis were significant risk factors (HR 1.075 and 41.393, both P ​< ​0.01). The APRI score significantly improved at follow-up compared to baseline (0.53 vs. 0.25, P ​< ​0.001), and cirrhosis prevalence decreased from 5.70% to 0.88% (P ​< ​0.001). In conclusion, patients who achieved HBsAg clearance and discontinued Peg-IFN α treatment have a low risk of liver adverse events, while advanced age and cirrhosis remain major risk factors.
为探讨聚乙二醇化干扰素α (Peg-IFN α)治疗后hbv表面抗原(HBsAg)清除的慢性乙型肝炎患者发生长期肝脏不良事件的危险因素及影响因素,回顾性分析2008年至2023年北京地坛医院456例HBsAg清除后停用Peg-IFN α治疗的患者。基线定义为HBsAg清除和停止治疗的时间。终点是首次发生肝脏不良事件(肝细胞癌或腹水)或最后一次随访。随后,我们评估了肝脏不良事件的发生率和危险因素,以及肝纤维化、肝硬化和肝功能指标的变化。在中位随访70个月期间,肝脏不良事件发生率为2.30%,肝细胞癌发生率为1.76%,腹水发生率为0.55%。年龄较大、肝硬化为重要危险因素(HR 1.075、41.393,P均< 0.01)。与基线相比,APRI评分在随访时显著提高(0.53 vs. 0.25, P < 0.001),肝硬化患病率从5.70%降至0.88% (P < 0.001)。总之,获得HBsAg清除并停止Peg-IFN α治疗的患者肝脏不良事件的风险较低,而高龄和肝硬化仍然是主要的危险因素。
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引用次数: 0
Co-circulation of all four DENV serotypes during 2016 outbreak in Sinaloa, Mexico: First report of DENV-4 in patients 墨西哥锡那罗亚州2016年疫情期间登革热病毒所有四种血清型的共循环:首次报告DENV-4患者。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.010
Annete Itzel Apodaca-Medina , José Israel Torres-Avendaño , Hipólito Castillo-Ureta , Edith Hilario Torres-Montoya , Sergio Alonso Durán-Pérez , Lorenzo Ulises Osuna-Martínez , María Elena Báez-Flores , José Guadalupe Rendón-Maldonado
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引用次数: 0
Rapid and accurate detection of infectious SARS-CoV-2 by viral receptor capture combined with loop-mediated isothermal amplification 病毒受体捕获结合环介导等温扩增快速准确检测传染性SARS-CoV-2
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.06.006
Zixiao Yang , Xinrong Zhou , Xikui Sun , Liu Cao , Tiefeng Xu , Kun Li , Hongchao Liu , Yanxi Ji , Lihong Liu , Konstantin I. Ivanov , Zhonghan Yang , Deyin Guo , Chun-Mei Li
Rapid and accurate detection of infectious virus particles, not just viral nucleic acid, is essential to avoid unnecessary quarantine and effectively control the spread of viral diseases such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). Real-time quantitative polymerase chain reaction (RT-qPCR) was the most widely used detection technique during the COVID-19 outbreak. However, it cannot discriminate between intact infectious viruses and surface-distorted, non-infectious virus particles or naked viral RNA. In this study, we present a strategy for the specific detection of infectious coronaviruses by combining viral receptor capture and reverse transcription loop-mediated isothermal amplification (RT-LAMP). We successfully applied this strategy to detect infectious virus particles of the SARS-CoV-2 surrogate virus and the human coronavirus NL63 (HCoV-NL63). Virus particles were first captured on ELISA plates coated with the recombinant human angiotensin-converting enzyme 2 (hACE2) receptor. Viral RNA was then extracted from the particles and detected by RT-LAMP using virus-specific primers. In our experimental setting, the proposed method had a minimum detection limit (LOD) of 90 ​PFU/mL, sensitivity of 96.2%, and specificity of 100%. Our study provides a proof-of-concept that viral receptor capture combined with RT-LAMP can differentiate infectious coronaviruses from non-infectious virions or naked viral RNA. This paves the way for this virus detection strategy to become a mainstream tool for the management, prevention and control of epidemic coronavirus diseases.
快速准确地检测传染性病毒颗粒,而不仅仅是病毒核酸,对于避免不必要的隔离,有效控制2019冠状病毒病(COVID-19)、严重急性呼吸综合征(SARS)、中东呼吸综合征(MERS)等病毒性疾病的传播至关重要。实时定量聚合酶链反应(RT-qPCR)是疫情期间应用最广泛的检测技术。然而,它不能区分完整的传染性病毒和表面扭曲的非传染性病毒颗粒或裸露的病毒RNA。在这项研究中,我们提出了一种结合病毒受体捕获和逆转录环介导的等温扩增(RT-LAMP)的传染性冠状病毒特异性检测策略。我们成功地应用该策略检测了SARS-CoV-2代病毒和人类冠状病毒NL63 (HCoV-NL63)的感染性病毒颗粒。首先在包被重组人血管紧张素转换酶2 (hACE2)受体的ELISA板上捕获病毒颗粒。然后从颗粒中提取病毒RNA,并使用病毒特异性引物进行RT-LAMP检测。在我们的实验环境中,该方法的最低检测限(LOD)为90 PFU/mL,灵敏度为96.2%,特异性为100%。我们的研究提供了一个概念证明,病毒受体捕获结合RT-LAMP可以区分传染性冠状病毒与非传染性病毒粒子或裸病毒RNA。这为这一病毒检测策略成为管理、预防和控制冠状病毒传染病的主流工具铺平了道路。
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引用次数: 0
ARRDC3 promotes lysosome-mediated YAP degradation to inhibit enterovirus replication ARRDC3促进溶酶体介导的YAP降解以抑制肠道病毒复制。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.009
Xia Huang , Siyuan Wang , Yan Huang , Yue Wang , Guangchao Zang , Yan Liang , Juntong Liu , Xinyue Han , Jingjing Liao , Tingting Chen , Nan Lu , Guangyuan Zhang
Enterovirus D68 (EV-D68) and enterovirus A71 (EV-A71) are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks, yet their pathogenic mechanisms remain largely unexplored. Arrestin domain containing 3 (ARRDC3) is a vital regulator of glucose metabolism, cancer development, and inflammation. Whether ARRDC3 contributes to innate antiviral immunity is undefined. Here, we found that enterovirus infection induces ARRDC3 expression at both the mRNA and protein levels, thereby inhibiting enterovirus replication. Moreover, we demonstrate that the expression of Yes-associated protein (YAP), a key effector of the Hippo pathway, is severely downregulated by ARRDC3 via lysosomal pathway. YAP facilitates enterovirus replication by suppressing the interferon pathway during the later stage of enterovirus infection, independent of its transcriptional activity. Finally, the ARRDC3-YAP pathway exhibits a broad-spectrum antiviral effect in various viral infections, including those caused by human parainfluenza virus type 3 (HPIV3) and vesicular stomatitis virus (VSV). Collectively, our results identify the critical role of ARRDC3 and its negative regulatory effect on YAP in the innate antiviral response, suggesting a novel therapeutic strategy against virus infection.
肠病毒D68 (EV-D68)和肠病毒A71 (EV-A71)是对公共卫生构成新挑战并有可能引起暴发的两种主要肠道病毒类型,但其致病机制在很大程度上仍未被探索。抑制蛋白结构域3 (ARRDC3)是葡萄糖代谢、癌症发展和炎症的重要调节因子。ARRDC3是否参与先天抗病毒免疫尚不明确。在这里,我们发现肠道病毒感染诱导ARRDC3 mRNA和蛋白水平的表达,从而抑制肠道病毒的复制。此外,我们证实了Hippo通路的关键效应物yes相关蛋白(YAP)的表达被ARRDC3通过溶酶体途径严重下调。在肠病毒感染的后期,YAP通过抑制干扰素途径促进肠病毒复制,而不依赖于其转录活性。最后,ARRDC3-YAP通路在各种病毒感染中显示出广谱抗病毒作用,包括由人类副流感病毒3型(HPIV3)和水疱性口炎病毒(VSV)引起的病毒感染。总的来说,我们的研究结果确定了ARRDC3在先天抗病毒反应中的关键作用及其对YAP的负调控作用,为对抗病毒感染提供了一种新的治疗策略。
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引用次数: 0
Quercetin inhibits herpes simplex virus 1 replication in corneal epithelium and suppresses keratitis progression 槲皮素抑制单纯疱疹病毒1型在角膜上皮中的复制并抑制角膜炎进展。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.007
Yubin Yu , Sihao Liu , Qinghua Liu , Xiuping Liu , Kaili Wu
Quercetin is a natural compound with potent antiviral effects; however, its role in the treatment of herpes simplex keratitis (HSK) remains underexplored. Here, we investigated the antiviral effects of quercetin against herpes simplex virus 1 (HSV-1). By examining different phases of viral infection in human corneal epithelial cells (HCECs), we found that 30 μmol/L quercetin inhibits HSV-1 replication primarily by disrupting viral attachment. RNA-sequencing and subsequent analyses revealed that the nuclear factor E2-related factor 2 (Nrf2) was upregulated by quercetin in a dose-dependent manner. Knocking down Nrf2 partially compromised quercetin's antiviral effect. Importantly, topical application of 100 μmol/L quercetin alleviated HSK severity in mice, reduced viral titers in tears, and inhibited VP16 expression in the cornea and trigeminal ganglia. These findings demonstrate the antiviral effect of quercetin against HSV-1 and provide a foundation for mechanistic studies to elucidate its therapeutic potential in HSK.
槲皮素是一种具有有效抗病毒作用的天然化合物;然而,其在治疗单纯疱疹性角膜炎(HSK)中的作用仍未得到充分探讨。本文研究了槲皮素对单纯疱疹病毒1型(HSV-1)的抗病毒作用。通过检测病毒感染人角膜上皮细胞(HCECs)的不同阶段,我们发现30 μmol/L槲皮素主要通过破坏病毒附着来抑制HSV-1的复制。rna测序和随后的分析显示,核因子e2相关因子2 (Nrf2)以剂量依赖的方式被槲皮素上调。敲除Nrf2部分削弱了槲皮素的抗病毒作用。重要的是,外用100 μmol/L槲皮素可减轻小鼠HSK的严重程度,降低泪液中的病毒滴度,抑制角膜和三叉神经节中VP16的表达。这些发现证实了槲皮素对HSV-1的抗病毒作用,为阐明其治疗HSK的机制研究奠定了基础。
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引用次数: 0
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Virologica Sinica
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