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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
The slow progression of Japanese encephalitis in aged mice is likely associated to B cell recruitment in the brain 老年小鼠乙型脑炎的缓慢进展可能与脑内B细胞募集有关。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.05.013
Zheng-Ran Song , Yi-Lin Yang , Yang Zhou , Li-Bo Liu , Fei-Yang Xue , Lin-Shen-Yang Liu , Na Gao , Dong-Ying Fan , Yi-Song Wang , Jing An , Pei-Gang Wang
The Japanese encephalitis virus (JEV) causes Japanese encephalitis (JE), a severe disease that primarily affects children and induces significant central nervous system complications. With the widespread adoption of vaccination in children, the incidence among older individuals has increased substantially. Despite this epidemiological shift, research on JEV infection in the elderly remains limited. We established JEV infection models using both aged and young mice to explore age-related differences in pathology and underlying mechanisms. Brain tissue samples were analyzed for pathological changes and viral tropism in major cell types. To further characterize immune response variations, we conducted transcriptomic sequencing on the brain tissues following JEV infection. Aged mice exhibited lower mortality, delayed disease progression, and milder brain pathology compared to young mice after JEV infection. Viral titers and infection rates of major brain cell types were similar in both groups. Transcriptomic analysis revealed diminished immune activation and weaker inflammatory responses in aged mice. Additionally, microglial activation and CD8+ T cell function were significantly reduced. Interestingly, JEV infection induced the selective recruitment of B cells in the brains of aged mice. These B cells may modulate the effects of CD8+ T cells in the disease process. Compared to young mice, aged mice showed enhanced resistance to JEV progression and reduced brain pathology. This resistance was associated with a weakened immune response in the aged brain, rather than differences in viral infection. The specific recruitment of B cells in the brains of aged mice may play a crucial role in limiting disease progression.
日本脑炎病毒(JEV)引起日本脑炎(JE),这是一种主要影响儿童并诱发严重中枢神经系统并发症的严重疾病。随着儿童广泛接种疫苗,老年人的发病率大大增加。尽管有这种流行病学转变,但对老年人乙脑病毒感染的研究仍然有限。我们使用老年和年轻小鼠建立了乙脑感染模型,以探索年龄相关的病理差异和潜在机制。分析脑组织样本的病理变化和主要细胞类型的病毒趋向性。为了进一步表征免疫反应的变化,我们对乙脑病毒感染后的脑组织进行了转录组测序。与年轻小鼠相比,老年小鼠在感染乙脑病毒后表现出较低的死亡率、延迟的疾病进展和较轻的脑病理。两组主要脑细胞类型的病毒滴度和感染率相似。转录组学分析显示,老年小鼠免疫激活减弱,炎症反应减弱。此外,小胶质细胞活化和CD8+ T细胞功能显著降低。有趣的是,乙脑病毒感染诱导了老年小鼠大脑中B细胞的选择性募集。这些B细胞可能调节CD8+ T细胞在疾病过程中的作用。与年轻小鼠相比,老年小鼠对乙脑病毒进展的抵抗力增强,脑部病理减少。这种抵抗力与衰老大脑的免疫反应减弱有关,而与病毒感染的差异无关。老年小鼠大脑中B细胞的特异性募集可能在限制疾病进展中起关键作用。
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引用次数: 0
Identification of PEDV inhibitors targeting 3CL protease 靶向3CL蛋白酶的PEDV抑制剂的鉴定。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.06.002
Ang Tian , Shutong Shi , Siying Zou , Shuaiyin Guan , Hao Wu , Zhen Li , Huanchun Chen , Yunfeng Song
Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), is a highly contagious gastrointestinal disease characterized by vomiting, diarrhea, and dehydration, with mortality rates approaching 100% among suckling piglets. The PEDV 3C-like protease (3CLpro) is essential for viral replication and regarded as a critical target for antiviral inhibitor development. In this study, we aimed to identify small-molecule inhibitors of PEDV by targeting 3CLpro. Virtual screening of 1.6 million compounds from the ChemDiv library identified four potential candidates. Molecular dynamics simulations, specifically analyzing RMSD, RMSF, and Rg, demonstrated increased structural stability of the compound-protease complexes compared to the monomeric enzyme. All compounds had low cytotoxicity in Vero cells (CC50 ​> ​200 ​μM). Fluorescence resonance energy transfer-based assays demonstrated dose-dependent inhibitory activity of the compounds against 3CLpro. Among the candidates, compound F366-0161 exhibited the weakest inhibition, with an IC50 value of 151.5 ​μM. Two analogues, 3238-0395 (IC50 of 121.4 ​μM) and L878-0493 (IC50 of 123.6 ​μM), exhibited moderately enhanced activity. Y041-1672 was identified as the most effective inhibitor, with an IC50 of 86.48 ​μM. In viral replication inhibition assays, Y041-1672 reduced PEDV replication, with an EC50 of 17.97 ​μM and a selectivity index (SI) of 15.5 (CC50/EC50). These results were validated by RT-qPCR, plaque assays, immunofluorescence, and Western blot analyses. In vitro validation confirmed Y041-1672 as the optimal antiviral candidate, and time-of-addition experiments indicated that inhibition primarily occurred during viral replication. This study identifies scaffold molecules for PEDV antiviral drug development, providing strategic insights for PED treatment.
猪流行性腹泻(PED)是由猪流行性腹泻病毒(PEDV)引起的一种以呕吐、腹泻和脱水为特征的高度传染性胃肠道疾病,在哺乳仔猪中死亡率接近100%。PEDV 3c样蛋白酶(3CLpro)对病毒复制至关重要,被认为是抗病毒抑制剂开发的关键靶点。在本研究中,我们旨在以3CLpro为靶点,鉴定PEDV的小分子抑制剂。对ChemDiv文库中的160万种化合物进行虚拟筛选,确定了四种潜在的候选化合物。分子动力学模拟(RMSD, RMSF, Rg)表明,与单体酶相比,复合蛋白酶复合物的结构稳定性增强。所有化合物在Vero细胞中具有较低的细胞毒性(CC50 ~ 200 μM)。基于荧光共振能量转移的分析显示化合物对3CLpro的抑制活性呈剂量依赖性。其中化合物F366-0161的抑制作用最弱,IC50值为151.5 μM。两个类似物3238-0395 (IC50为121.4 μM)和L878-0493 (IC50为123.6 μM)表现出适度增强的活性。Y041-1672是最有效的抑制剂,IC50为86.48 μM。在病毒复制抑制实验中,Y041-1672降低PEDV复制,EC50为17.97 μM,选择性指数(SI)为15.5 (CC50/EC50)。这些结果通过RT-qPCR、斑块分析、免疫荧光和Western blot分析得到验证。体外验证证实Y041-1672是最佳抗病毒候选,添加时间实验表明抑制主要发生在病毒复制过程中。本研究确定了用于PEDV抗病毒药物开发的支架分子,为PED治疗提供了战略见解。
{"title":"Identification of PEDV inhibitors targeting 3CL protease","authors":"Ang Tian ,&nbsp;Shutong Shi ,&nbsp;Siying Zou ,&nbsp;Shuaiyin Guan ,&nbsp;Hao Wu ,&nbsp;Zhen Li ,&nbsp;Huanchun Chen ,&nbsp;Yunfeng Song","doi":"10.1016/j.virs.2025.06.002","DOIUrl":"10.1016/j.virs.2025.06.002","url":null,"abstract":"<div><div>Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), is a highly contagious gastrointestinal disease characterized by vomiting, diarrhea, and dehydration, with mortality rates approaching 100% among suckling piglets. The PEDV 3C-like protease (3CLpro) is essential for viral replication and regarded as a critical target for antiviral inhibitor development. In this study, we aimed to identify small-molecule inhibitors of PEDV by targeting 3CLpro. Virtual screening of 1.6 million compounds from the ChemDiv library identified four potential candidates. Molecular dynamics simulations, specifically analyzing RMSD, RMSF, and Rg, demonstrated increased structural stability of the compound-protease complexes compared to the monomeric enzyme. All compounds had low cytotoxicity in Vero cells (CC<sub>50</sub> ​&gt; ​200 ​μM). Fluorescence resonance energy transfer-based assays demonstrated dose-dependent inhibitory activity of the compounds against 3CLpro. Among the candidates, compound F366-0161 exhibited the weakest inhibition, with an IC<sub>50</sub> value of 151.5 ​μM. Two analogues, 3238-0395 (IC<sub>50</sub> of 121.4 ​μM) and L878-0493 (IC<sub>50</sub> of 123.6 ​μM), exhibited moderately enhanced activity. Y041-1672 was identified as the most effective inhibitor, with an IC<sub>50</sub> of 86.48 ​μM. In viral replication inhibition assays, Y041-1672 reduced PEDV replication, with an EC<sub>50</sub> of 17.97 ​μM and a selectivity index (SI) of 15.5 (CC<sub>50</sub>/EC<sub>50</sub>). These results were validated by RT-qPCR, plaque assays, immunofluorescence, and Western blot analyses. <em>In vitro</em> validation confirmed Y041-1672 as the optimal antiviral candidate, and time-of-addition experiments indicated that inhibition primarily occurred during viral replication. This study identifies scaffold molecules for PEDV antiviral drug development, providing strategic insights for PED treatment.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 4","pages":"Pages 624-635"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Differential susceptibility of immunodeficient mice to MPXV infection and the impact of various inoculation routes 免疫缺陷小鼠对MPXV感染的差异易感性及不同接种途径的影响。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.04.001
Xiaohan Wang , Shaowen Shi , Xiaoxuan Nie , Yongyang Sun , Jinglei Hu , Manlin He , Wenhao Ren , Yuxing Wang , Zhendong Guo , Gonghe Li , Changbo Ou , Xiao Li , Zongzheng Zhao
Monkeypox virus (MPXV), a member of the Orthopoxvirus genus, caused a large-scale global outbreak in 2022. Developing mouse models for MPXV infection is crucial for advancing research on vaccines and therapeutic interventions. To address this, we conducted a comparative study on the susceptibility of six mouse strains—severe combined immune-deficiency (SCID), nude, genetically diabetic (db/db) and obese (ob/ob), C57BL/6J, and BALB/c—to MPXV infection. Mouse strains were infected with MPXV via intranasal inoculation, and body weight changes and mortality were monitored post-infection. Additionally, the tissue distribution of MPXV and the pathological changes in the lung tissues of the infected mice were evaluated. The results demonstrated that SCID and nude mice exhibited significant weight loss following MPXV infection, with 100 ​% mortality observed in SCID mice, while no mortality occurred in nude mice. In contrast, the other mouse strains showed no significant weight loss or mortality. Notably, the viral load in the lung tissues of SCID and nude mice was the highest among the tested strains. Furthermore, we investigated the impact of different inoculation routes—intranasal (I.N.), intraperitoneal (I.P.), and intravenous (I.V.)—on the pathogenicity of MPXV in mice. The results revealed that the intravenous route induced more pronounced pathogenic effects compared to the intranasal and intraperitoneal routes. In summary, this study provides valuable insights into the development of MPXV-infected mouse models, offering a foundation for further research on MPXV pathogenesis and therapeutic drug development.
猴痘病毒(MPXV)是正痘病毒属的一员,在2022年引起了大规模的全球疫情。开发MPXV感染的小鼠模型对于推进疫苗和治疗干预的研究至关重要。为了解决这个问题,我们对6种小鼠品系——严重联合免疫缺陷(SCID)、裸鼠、遗传性糖尿病(db/db)和肥胖(ob/ob)、C57BL/6J和BALB/c——对MPXV感染的易感性进行了比较研究。通过鼻内接种MPXV感染小鼠品系,监测感染后的体重变化和死亡率。观察MPXV的组织分布及感染小鼠肺组织的病理变化。结果表明,MPXV感染后,SCID和裸鼠体重明显减轻,SCID小鼠死亡率为100%,而裸鼠没有死亡。相比之下,其他小鼠品系没有表现出明显的体重减轻或死亡率。值得注意的是,SCID和裸鼠肺组织的病毒载量最高。此外,我们研究了不同的接种途径-鼻内(I.N.),腹腔(I.P.)和静脉(I.V.)-对小鼠MPXV致病性的影响。结果表明,与鼻内和腹腔途径相比,静脉途径诱导的致病作用更明显。综上所述,本研究为MPXV感染小鼠模型的建立提供了有价值的见解,为进一步研究MPXV的发病机制和治疗药物的开发提供了基础。
{"title":"Differential susceptibility of immunodeficient mice to MPXV infection and the impact of various inoculation routes","authors":"Xiaohan Wang ,&nbsp;Shaowen Shi ,&nbsp;Xiaoxuan Nie ,&nbsp;Yongyang Sun ,&nbsp;Jinglei Hu ,&nbsp;Manlin He ,&nbsp;Wenhao Ren ,&nbsp;Yuxing Wang ,&nbsp;Zhendong Guo ,&nbsp;Gonghe Li ,&nbsp;Changbo Ou ,&nbsp;Xiao Li ,&nbsp;Zongzheng Zhao","doi":"10.1016/j.virs.2025.04.001","DOIUrl":"10.1016/j.virs.2025.04.001","url":null,"abstract":"<div><div>Monkeypox virus (MPXV), a member of the <em>Orthopoxvirus</em> genus, caused a large-scale global outbreak in 2022. Developing mouse models for MPXV infection is crucial for advancing research on vaccines and therapeutic interventions. To address this, we conducted a comparative study on the susceptibility of six mouse strains—severe combined immune-deficiency (SCID), nude, genetically diabetic (db/db) and obese (ob/ob), C57BL/6J, and BALB/c—to MPXV infection. Mouse strains were infected with MPXV via intranasal inoculation, and body weight changes and mortality were monitored post-infection. Additionally, the tissue distribution of MPXV and the pathological changes in the lung tissues of the infected mice were evaluated. The results demonstrated that SCID and nude mice exhibited significant weight loss following MPXV infection, with 100 ​% mortality observed in SCID mice, while no mortality occurred in nude mice. In contrast, the other mouse strains showed no significant weight loss or mortality. Notably, the viral load in the lung tissues of SCID and nude mice was the highest among the tested strains. Furthermore, we investigated the impact of different inoculation routes—intranasal (I.N.), intraperitoneal (I.P.), and intravenous (I.V.)—on the pathogenicity of MPXV in mice. The results revealed that the intravenous route induced more pronounced pathogenic effects compared to the intranasal and intraperitoneal routes. In summary, this study provides valuable insights into the development of MPXV-infected mouse models, offering a foundation for further research on MPXV pathogenesis and therapeutic drug development.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 333-339"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of a SARS-CoV-2 infection model in golden hamsters with diabetes mellitus 糖尿病金仓鼠SARS-CoV-2感染模型的建立
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.05.001
Hao-Feng Lin , Ren-Di Jiang , Rui-Xin Qin , Bing Yao , Wen-Tao Zeng , Yun Gao , Ai-Min Shi , Jian-Min Li , Mei-Qin Liu
Being widespread across the globe, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and generating new variants and continuously poses threat to public health, especially to the population with chronic comorbidities. Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019 (COVID-19). Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential. Here, in this study, we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus (db/db), and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters. SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters. Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters, and may induce serious complications such as diabetic kidney disease and cardiac lesions. Our findings demonstrated that despite the decreased respiratory pathogenicity, the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters, suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected. This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes. It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)在全球广泛传播,不断演变并产生新的变体,不断对公众健康构成威胁,特别是对患有慢性合并症的人群。糖尿病是2019冠状病毒病(COVID-19)严重结局的高危因素之一。因此,建立符合新冠肺炎合并糖尿病临床和病理特征的动物模型是非常必要的。在本研究中,我们构建了具有糖尿病表型(db/db)的瘦素受体基因敲除仓鼠,发现糖尿病型仓鼠比野生型仓鼠更容易感染SARS-CoV-2及其变体。SARS-CoV-2及其变体在糖尿病仓鼠的肺部诱导的免疫细胞因子反应比野生型仓鼠更强。比较组织病理学分析还显示,感染SARS-CoV-2及其变体可导致糖尿病仓鼠更严重的肺组织损伤,并可能诱发糖尿病肾病和心脏病变等严重并发症。我们的研究结果表明,尽管呼吸致病性降低,但SARS-CoV-2变异仍然能够损害糖尿病仓鼠的其他器官,如肾脏和心脏,这表明SARS-CoV-2变异对糖尿病患者的风险绝不应被忽视。该仓鼠模型可能有助于更好地了解糖尿病患者重症COVID-19的发病机制。它还将有助于在这些高风险人群中开发和测试针对SARS-CoV-2变体的有效疗法和预防性治疗。
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引用次数: 0
Human endogenous retrovirus W family envelope protein (ERVWE1) regulates macroautophagy activation and micromitophagy inhibition via NOXA1 in schizophrenia 人内源性逆转录病毒W家族包膜蛋白(ERVWE1)通过NOXA1调控精神分裂症大自噬激活和微自噬抑制。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.05.007
Jiahang Zhang , Huiling Wang , Xing Xue , Xiulin Wu , Wenshi Li , Zhao Lv , Yaru Su , Mengqi Zhang , Kexin Zhao , Xu Zhang , Chen Jia , Fan Zhu
The human endogenous retrovirus type W envelope glycoprotein (ERVWE1), located at chromosome 7q21–22, has been implicated in the pathophysiology of schizophrenia. Our previous studies have shown elevated ERVWE1 expression in schizophrenia patients. Growing evidence suggests that autophagy dysfunction contributes to schizophrenia, yet the relationship between ERVWE1 and autophagy remains unclear. In this study, bioinformatics analysis of the human prefrontal cortex RNA microarray dataset (GSE53987) revealed that differentially expressed genes were predominantly enriched in autophagy-related pathways. Clinical data further demonstrated that serum levels of microtubule-associated protein 1 light chain 3β (LC3B), a key marker of macroautophagy, were significantly elevated in schizophrenia patients compared to controls, and positively correlated with ERVWE1 expression. Cellular and molecular experiments suggested that ERVWE1 promoted macroautophagy by increasing the LC3B II/I ratio, enhancing autophagosome formation, and reducing sequestosome 1 (SQSTM1) expression via upregulation of NADPH oxidase activator 1 (NOXA1). Concurrently, NOXA1 downregulated the expression of key micromitophagy-related genes, including PTEN-induced kinase 1 (PINK1), Parkin RBR E3 ubiquitin-protein ligase (Parkin), and the pyruvate dehydrogenase E1 subunit α 1 (PDHA1). As a result, ERVWE1, via NOXA1, inhibited micromitophagy by suppressing the expression of PINK1, Parkin, and PDHA1, thereby leading to impaired production of mitochondrial-derived vesicles (MDVs). Mechanistically, ERVWE1 enhanced NOXA1 transcription by upregulating upstream transcription factor 2 (USF2). In conclusion, ERVWE1 promotes macroautophagy and inhibits micromitophagy through USF2-NOXA1 axis, providing novel mechanistic insight into the role autophagy dysregulation in schizophrenia. These findings suggest that targeting autophagy pathways may offer novel therapeutic strategies for schizophrenia treatment.
位于染色体7q21-22的人类内源性逆转录病毒型W包膜糖蛋白(ERVWE1)与精神分裂症的病理生理有关。我们之前的研究表明,ERVWE1在精神分裂症患者中表达升高。越来越多的证据表明,自噬功能障碍有助于精神分裂症,但ERVWE1与自噬之间的关系尚不清楚。在这项研究中,对人类前额叶皮层RNA微阵列数据集(GSE53987)的生物信息学分析显示,差异表达基因主要富集在自噬相关通路中。临床数据进一步表明,与对照组相比,精神分裂症患者血清巨噬的关键标志物微管相关蛋白1轻链3β (LC3B)水平显著升高,且与ERVWE1表达呈正相关。细胞和分子实验表明,ERVWE1通过上调NADPH氧化酶激活物1 (NOXA1),提高LC3B /I比值,增强自噬体形成,降低固溶体1 (SQSTM1)表达,从而促进大细胞自噬。同时,NOXA1下调微丝自噬相关关键基因的表达,包括pten诱导的激酶1 (PINK1)、Parkin RBR E3泛素蛋白连接酶(Parkin)和丙酮酸脱氢酶E1亚基α 1 (PDHA1)。因此,ERVWE1通过NOXA1通过抑制PINK1、Parkin和PDHA1的表达来抑制微丝自噬,从而导致线粒体源性囊泡(mdv)的产生受损。在机制上,ERVWE1通过上调上游转录因子2 (USF2)来增强NOXA1的转录。综上所述,ERVWE1通过USF2-NOXA1轴促进大自噬并抑制微自噬,为自噬失调在精神分裂症中的作用提供了新的机制见解。这些发现表明,靶向自噬途径可能为精神分裂症治疗提供新的治疗策略。
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引用次数: 0
Decoding the virome reveals diverse novel viruses in tree shrews (Tupaia belangeri) in Yunnan Province 解码病毒组揭示了云南省树鼩(图帕亚belangeri)中多种新型病毒。
IF 5.5 3区 医学 Q1 Medicine Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.05.011
Zhong-Hao Lian , Zhi You , Pei-Yu Han , Ye Qiu , Yun-Zhi Zhang , Xing-Yi Ge
Viruses circulating in small mammals possess the potential to infect humans. Tree shrews are a group of small mammals inhabiting widely in forests and plantations, but studies on viruses in tree shrews are quite limited. Herein, viral metagenomic sequencing was employed to detect the virome in the tissue and swab samples from seventy-six tree shrews that we collected in Yunnan Province. As the results, genomic fragments belonging to eighteen viral families were identified, thirteen of which contain mammalian viruses. Through polymerase chain reaction (PCR) and Sanger sequencing, twelve complete genomes were determined, including five parvoviruses, three torque teno viruses (TTVs), two adenoviruses, one pneumovirus, and one hepacivirus, together with three partial genomes, including two hepatitis E viruses and one paramyxovirus. Notably, the three TTVs, named TSTTV-HNU1, TSTTV-HNU2, and TSTTV-HNU3, may compose a new genus within the family Anelloviridae. Notably, TSParvoV-HNU5, one of the tree shrew parvoviruses detected, was likely to be a recombination of two murine viruses. Divergence time estimation further revealed the potential cross-species-transmission history of the tree shrew pneumovirus TSPneV-HNU1. Our study provides a comprehensive exploration of viral diversity in wild tree shrews, significantly enhancing our understanding of their roles as natural virus reservoirs.
在小型哺乳动物中传播的病毒有可能感染人类。树鼩是一种广泛生活在森林和人工林中的小型哺乳动物,但对树鼩病毒的研究相当有限。本文采用病毒宏基因组测序方法对云南省采集的76只树鼩组织和拭子样本中的病毒进行检测。结果,鉴定出了18个病毒科的基因组片段,其中13个含有哺乳动物病毒。通过聚合酶链反应(PCR)和Sanger测序,确定了12个完整基因组,包括5个细小病毒(parvovirus)、3个torque teno病毒(TTVs)、2个腺病毒、1个肺炎病毒和1个肝炎病毒,以及3个部分基因组,包括2个戊型肝炎病毒和1个副粘病毒。值得注意的是,被命名为TSTTV-HNU1、TSTTV-HNU2和TSTTV-HNU3的三个ttv可能组成了一个新的属。值得注意的是,发现的树鼩细小病毒之一TSParvoV-HNU5很可能是两种鼠病毒的重组。发散时间估计进一步揭示了树鼩肺炎病毒TSPenV-HNU1潜在的跨种传播史。我们的研究提供了对野生树鼩病毒多样性的全面探索,显著增强了我们对它们作为天然病毒宿主作用的理解。
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Virologica Sinica
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