Virologica Sinica最新文献_第9页

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

Virologica Sinica

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

Virologica Sinica

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。

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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

Virologica Sinica

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。

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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

Virologica Sinica

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

Virologica Sinica

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

Virologica Sinica

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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引用次数: 0

Issue Cover 覆盖问题

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-06-01 DOI: 10.1016/S1995-820X(25)00073-2

引用次数: 0

Corrigendum to “Evaluating the performance of the PREDAC method in flu vaccine recommendations over the past decade (2013–2023)” [Virol. Sin. 40 (2025) 288–291] “评估过去十年（2013-2023）PREDAC方法在流感疫苗推荐中的表现”的勘误表性研究。罪恶，40 (2025)288-291 [j]。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.06.001

Yousong Peng , Lei Yang , Weijuan Huang , Mi Liu , Xiao Ding , Xiangjun Du , Yuelong Shu , Taijiao Jiang , Dayan Wang

引用次数: 0

Nucleophosmin 1 inhibits the replication of influenza A virus by competitively binding viral RNA with viral proteins 核磷蛋白1通过竞争性结合病毒RNA与病毒蛋白抑制甲型流感病毒的复制。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.04.007

Yingying Yu , Qian Wang , Yanli Wei , Junwen Liu , Guangwen Wang , Zhengxiang Wang , Wentao Shen , Lu Han , Chengjun Li , Cao-Qi Lei , Shuai Xu , Qiyun Zhu

Influenza A viruses (IAVs) are single-stranded negative-sense RNA viruses that continually challenge animal and human health. In IAV-infected cells, host RNA-binding proteins play key roles in the life cycle of IAV by directly binding to viral RNA. Here, we examined the role of the host RNA-binding protein nucleophosmin-1 (NPM1) in IAV replication. We found that, as a nucleolar phosphoprotein, NPM1 directly binds to viral RNA (vRNA) and inhibits the replication of various subtypes of IAV. NPM1 binding to vRNA competitively reduces the assembly of the viral ribonucleoprotein complex and the viral polymerase activity, thereby reducing the generation of progeny viral RNA and virions. The RNA-binding activity of NPM1, with the key residues T199, T219, T234, and T237, is essential for its anti-influenza function. Taken together, our findings demonstrate that NPM1 acts as an RNA-binding protein and interacts with IAV vRNA to suppress viral replication.

甲型流感病毒（iav）是单链负义RNA病毒，不断威胁动物和人类的健康。在IAV感染的细胞中，宿主RNA结合蛋白通过直接与病毒RNA结合，在IAV的生命周期中发挥关键作用。在这里，我们研究了宿主rna结合蛋白核磷蛋白-1 （NPM1）在IAV复制中的作用。我们发现，NPM1作为一种核仁磷酸化蛋白，可直接与病毒RNA （vRNA）结合，抑制多种IAV亚型的复制。NPM1与vRNA的结合竞争性地降低了病毒核糖核蛋白复合物的组装和病毒聚合酶的活性，从而减少了子代病毒RNA和病毒粒子的产生。NPM1与关键残基T199、T219、T234和T237的rna结合活性对其抗流感功能至关重要。综上所述，我们的研究结果表明NPM1作为一种rna结合蛋白，与IAV vRNA相互作用，抑制病毒复制。

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引用次数: 0

Viral pseudo-enzyme facilitates KSHV lytic replication via suppressing PFAS-mediated RTA deamidation 病毒伪酶通过抑制pfas介导的RTA脱酰胺促进KSHV裂解复制。

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.04.005

Yang Xu , Qiushi Zhang , Guoli Hou , Liang Hu , Tiaoyi Xiao , Xinyu Liang , Deliang Li , Junhua Li

Deamidation, a type of post-translational modification commonly considered a hallmark of protein “aging” and function decay, is increasingly recognized for its pivotal role in regulating biological processes and viral infection. Our previous study has demonstrated that the deamidation of replication and transcription activator (RTA), a master regulator of ubiquitous and oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV), mediated by phosphoribosylformylglycinamidine synthetase (PFAS), hinders its nuclear import and transcriptional activity. Here we report that the viral glutamine amidotransferase (vGAT) pseudo-enzyme is exploited to facilitate KSHV lytic infection by inhibiting RTA deamidation. To be more specific, vGAT interacts with both RTA and cellular PFAS, and inhibits PFAS-mediated RTA deamidation, thus facilitating RTA nuclear localization and suppressing nuclear factor-kappa B (NF-κB) signaling activation, as well as augmenting RTA-mediated transcriptional activation of viral open reading frames (ORFs). In addition, vGAT appears to regulate the deamidation process of several viral ORFs of KSHV. Collectively, these findings unveil that a viral pseudo-enzyme is exploited to enhance viral infection via deamidation regulation.

脱酰胺是一种翻译后修饰，通常被认为是蛋白质“老化”和功能衰退的标志，它在调节生物过程和病毒感染方面的关键作用越来越得到认可。我们之前的研究表明，由磷酸核糖基甲酰基甘氨酸合成酶（PFAS）介导的复制和转录激活因子（RTA）的脱酰胺化阻碍了其核输入和转录活性。RTA是普遍存在的致癌卡波西肉瘤相关疱疹病毒（KSHV）的主要调节因子。本文报道利用病毒谷氨酰胺氨基转移酶（vGAT）伪酶抑制RTA脱酰胺，促进KSHV裂解感染。更具体地说，vGAT与RTA和细胞PFAS相互作用，抑制PFAS介导的RTA脱酰胺，从而促进RTA核定位，抑制核因子κB （NF-κB）信号激活，并增强RTA介导的病毒开放阅读框（orf）的转录激活。此外，vGAT似乎调节了几种KSHV病毒orf的脱酰胺过程。总的来说，这些发现揭示了一种病毒伪酶通过脱酰胺调节来增强病毒感染。

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引用次数: 0