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On the brink of emergence: an evolutionary approach to Influenza A virus H5N1 isolated from humans. 在出现的边缘:从人类分离的甲型流感病毒H5N1的进化方法。
IF 2.7 4区 医学 Q3 VIROLOGY Pub Date : 2026-03-21 DOI: 10.1016/j.virusres.2026.199717
Irene Ferreiro, Joaquín Hurtado, Alfredo Bruno, Juan Cristina

Avian Influenza Viruses (AIVs) pose today a very significant risk to global health given the widespread circulation of H5N1 highly pathogenic avian influenza viruses (HPAIV). After decimating the avian population all over the world, these viruses spill over to many different mammal species, causing also fatal outbreaks. As the virus continues to evolve increasing human cases of H5N1 HPAIV have been reported, causing concern that these viruses may adapt to the human host and became a pandemic new virus. In order to gain insight into this matter, a detailed phylogenetic analysis of H5N1 HPAIV isolated from humans was performed. A significant number of substitutions have been found in the hemagglutinins (HA) and neuraminidases (NA) among the three H5N1 clades already detected in human cases. Some of these substitutions were found to produce changes in the 3D structure of these proteins. Substitutions providing an evolutionary advantage to replicate or evade the immune response in mammals have been found in several non-structural proteins of strains infecting humans, including regulatory proteins, like PA-X or PB1-F2. A significant degree of polymorphic sites was observed in the proteins of the polymerase complex. The results of these studies are discussed in terms of the evolution of H5N1 HPAIV infecting humans and future work to be done to address the pandemic potential of these viruses.

鉴于H5N1高致病性禽流感病毒(HPAIV)的广泛传播,禽流感病毒(aiv)今天对全球卫生构成非常重大的风险。在全世界的鸟类数量大量减少之后,这些病毒扩散到许多不同的哺乳动物物种,也造成了致命的爆发。随着病毒继续进化,报告了越来越多的H5N1 HPAIV人间病例,令人担心这些病毒可能适应人类宿主并成为一种大流行的新病毒。为了深入了解这一问题,对从人类分离的H5N1型HPAIV进行了详细的系统发育分析。在已在人病例中检测到的3个H5N1进化支中,在血凝素(HA)和神经氨酸酶(NA)中发现了大量替换。其中一些取代被发现会改变这些蛋白质的三维结构。在哺乳动物中,在感染人类的菌株的几种非结构蛋白中发现了替代,这些替代为复制或逃避免疫反应提供了进化优势,包括调节蛋白,如PA-X或PB1-F2。在聚合酶复合体的蛋白质中观察到显著程度的多态性位点。从感染人类的H5N1型HPAIV的演变和今后为解决这些病毒的大流行潜力所要做的工作的角度讨论了这些研究的结果。
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引用次数: 0
First Report on Leucocytes Cell Population Data as an Applicable Test for Clinical Stratification in People Living with HIV. 白细胞群数据作为艾滋病毒感染者临床分层的适用测试的第一份报告。
IF 2.7 4区 医学 Q3 VIROLOGY Pub Date : 2026-03-20 DOI: 10.1016/j.virusres.2026.199716
Haidi Karam-Allah Ramadan, Aml A Rayan, Zeinab R Mohamed, Mohammed Ezz-Eldin, Ahmed A Kotb, Mohamed Ahmed, Rasha Assad Assiri, Salwa Seif Eldin, Amal A Elkhawaga

Background: Leucocytes cell population data (CPD) parameters have been applied in diagnosis and prognosis of viral infections. We aim to explore pattern of leucocytes CPD in people living with HIV (PLWH) and its role in clinical stratification.

Methods: This study included treatment-naïve PLWH and healthy control. Clinical HIV stages were determined. Laboratory assessment was conducted using complete blood picture, CPD, CD4+ T cells count, and HIV RNA testing. Correlation between CPD with CD4+ and HIV RNA was evaluated.

Results: A total of 125 were recruited; 70 cases and 55 control. Age and gender were not significantly different. WHO stage 3 was predominant at 34.29% and half of PLWH had advanced HIV. CPD parameters of neutrophils, lymphocytes and monocytes composition were significantly higher in PLWH. Parameters of neutrophils nucleic acid contents, lymphocytes dispersion of nucleic acid contents, and both neutrophils and lymphocytes size were significantly higher in PLWH. CD4+ T cells count positively correlated with WBCs, lymphocytes and monocytes count and size, but negatively correlated with lymphocytes composition, nucleic acid contents, and size, and both monocytes and neutrophils composition and nucleic acid contents. Viral load negatively correlated with neutrophils size.

Conclusion: CPD can be a cost-effective quantitative tool reflecting immune depletion in HIV. By decoding these parameters, clinicians can stratify PLWH risk of disease progression beyond CD4+ T cells count and viral load.

背景:白细胞群数据(CPD)参数已被应用于病毒感染的诊断和预后。我们旨在探讨HIV感染者(PLWH)白细胞CPD的模式及其在临床分层中的作用。方法本研究包括treatment-naïve PLWH和健康对照。确定临床HIV分期。使用全血图像、CPD、CD4+ T细胞计数和HIV RNA检测进行实验室评估。评估CPD与CD4+和HIV RNA的相关性。结果:共纳入125例;70例,对照组55例。年龄、性别差异不显著。以WHO期3期为主,占34.29%,其中半数感染者为晚期HIV。中性粒细胞、淋巴细胞和单核细胞组成的CPD参数在PLWH中显著升高。中性粒细胞核酸含量、淋巴细胞核酸含量弥散度、中性粒细胞和淋巴细胞大小等指标在PLWH组均显著升高。CD4+ T细胞计数与白细胞、淋巴细胞和单核细胞计数及大小正相关,与淋巴细胞组成、核酸含量及大小负相关,与单核细胞和中性粒细胞组成及核酸含量负相关。病毒载量与中性粒细胞大小负相关。结论:CPD是反映HIV免疫损耗的一种经济有效的定量工具。通过解码这些参数,临床医生可以对CD4+ T细胞计数和病毒载量以外的PLWH疾病进展风险进行分层。
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引用次数: 0
Honey bee hygienic selection impacts virus dynamics of both bees and Varroa mites. 蜜蜂卫生选择对蜜蜂和瓦螨的病毒动态都有影响。
IF 2.7 4区 医学 Q3 VIROLOGY Pub Date : 2026-03-17 DOI: 10.1016/j.virusres.2026.199715
Esmaeil Amiri, Somayeh Mehrparvar, Bita Valizadeh, Kaira Wagoner

The Varroa mite (Varroa destructor) has reshaped the viral landscape of honey bee colonies, significantly contributing to colony mortality. In response, Varroa-resistant honey bee breeding programs have developed as a promising and sustainable long-term strategy to control Varroa mite infestations in managed colonies. These breeding programs drive the coevolution of hygienic bees and Varroa mites, however the impact of such coevolution on bee and mite viral dynamics remains poorly understood. To address this gap, we investigated how Varroa-resistant traits influence the tripartite interaction among honey bees, Varroa mites, and viruses. Two apiaries were established: one in Greensboro, North Carolina, consisting of high and low UBeeO colonies, and another in Stoneville, Mississippi, consisting of Pol-line and Commercial colonies. Worker bees and Varroa mites were collected from each colony throughout the beekeeping season and screened for 7 viruses. Hygienic selection significantly reduced the Varroa mite infestation level and influenced the dynamics of viruses in worker bees and Varroa mites. Specifically, titers of Varroa-associated viruses were significantly reduced in worker bees and in mites collected from hygienic colonies. Additionally, hygienic selection altered the co-occurrence patterns and correlations among multiple critically important viruses in mites and worker bees. These findings highlight the value of selective breeding as an effective strategy for improving honey bee health and colony survival and shed light on the complex tripartite relationships between honey bees, Varroa mites, and viruses.

瓦螨(瓦螨破坏者)已经重塑了蜂群的病毒景观,显著地促进了蜂群的死亡。因此,抗瓦螨的蜜蜂育种计划已经发展成为一种有希望和可持续的长期战略,以控制管理蜂群中的瓦螨侵扰。这些繁殖计划推动了卫生蜜蜂和瓦螨的共同进化,然而这种共同进化对蜜蜂和螨病毒动力学的影响仍然知之甚少。为了解决这一差距,我们研究了抗瓦螨性状如何影响蜜蜂、瓦螨和病毒之间的三方相互作用。建立了两个养蜂场:一个在北卡罗来纳州的格林斯博罗,由高低UBeeO殖民地组成,另一个在密西西比州的斯通维尔,由polline和商业殖民地组成。在整个养蜂季节采集每个蜂群的工蜂和瓦螨,筛选7种病毒。卫生选择显著降低了工蜂和瓦螨的侵害水平,影响了病毒在工蜂和瓦螨中的动态。具体来说,在工蜂和从卫生菌落收集的螨虫中,瓦螨相关病毒的滴度显著降低。此外,卫生选择改变了螨和工蜂中多种重要病毒的共现模式和相关性。这些发现突出了选择性育种作为改善蜜蜂健康和群体生存的有效策略的价值,并揭示了蜜蜂、瓦螨和病毒之间复杂的三方关系。
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引用次数: 0
Virome of the fungi associated with mushroom dry bubble disease. 蘑菇干泡病相关真菌的病毒组。
IF 2.7 4区 医学 Q3 VIROLOGY Pub Date : 2026-03-17 DOI: 10.1016/j.virusres.2026.199714
Lóránt Hatvani, Sakae Hisano, Hideki Kondo, Hitomi Sugahara, Paul Telengech, Sabitree Shahi, Sarah Remi Ibiang, Sándor Kocsubé, Tünde Kartali, David A Fitzpatrick, Helen Grogan, Nobuhiro Suzuki

Dry bubble disease, attributed to the filamentous fungus Lecanicillium fungicola (Cordycipitaceae) results in huge yield losses in mushroom (Agaricus bisporus) cultivation worldwide. The possibilities for controlling the disease using commercial fungicides are highly limited, and therefore, there is an increasing demand for novel, alternative means of pest management. Our research objective was the comprehensive examination of viruses in the causal agents of dry bubble disease, which may open up an avenue for its virocontrol in the future. Out of 57 fungal isolates obtained from dry bubble-affected A. bisporus crops in various countries, 47 (82%) were confirmed by ITS (Internal Transcribed Spacer) sequence analysis as L. fungicola. In addition, different members of the genera Akanthomyces and Simplicillium (7 and 3 isolates, respectively), yet unknown to cause dry bubble symptoms, have also been detected. Cellulose column chromatography revealed the presence of double-stranded (ds) RNA in seven L. fungicola and three Akanthomyces sp. isolates, suggesting viral infection. The ten dsRNA-positive and eight randomly selected dsRNA-negative fungal strains were subjected to rRNA-depletion high-throughput RNA-sequencing analysis. The presence of seven new viruses representing four new species in the established families, Partitiviridae, Polymycoviridae, Botourmiaviridae and the narna-like virus group, and three previously established/proposed species in the families Chrysoviridae and "Mycovirgaviridae" were confirmed. The impact of the detected and identified viruses on their host fungi, and their potential applicability for virocontrol purposes will be examined in the future. This study provides the first detailed report on viruses of mushroom pathogenic fungi.

干泡病是由丝状真菌Lecanicillium fungicola(虫草科)引起的,在世界范围内造成蘑菇(Agaricus bisporus)种植的巨大产量损失。使用商业杀菌剂控制这种疾病的可能性非常有限,因此,对新的虫害管理替代手段的需求日益增加。我们的研究目的是全面研究干泡病致病因子中的病毒,为今后干泡病的病毒防治开辟一条途径。从57株受干泡影响的双孢单胞菌(A. bisporus)中分离得到的真菌中,47株(82%)经ITS (Internal转录间隔器)序列分析证实为L. fungicola。此外,还发现了Akanthomyces属和Simplicillium属的不同成员(分别为7个和3个分离株),但尚未发现它们会引起干泡症状。纤维素柱色谱分析结果显示,7株真菌菌和3株赤色菌中存在双链RNA,提示是病毒感染。随机选取10株dsrna阳性和8株dsrna阴性的真菌菌株进行rrna耗尽高通量rna测序分析。在已建立的分病毒科、多分枝病毒科、肉毒杆菌病毒科和narna样病毒群中发现了7种新病毒,并在黄病毒科和“分枝virgaviridae”科中发现了3种新病毒。检测和鉴定的病毒对其宿主真菌的影响,以及它们在病毒控制目的方面的潜在适用性,将在未来进行研究。本研究首次详细报道了蘑菇病原真菌的病毒。
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引用次数: 0
New clinical experiences and Echocardiography findings in COVID-19 elderly patients: 2019-2024 2019-2024年老年COVID-19患者临床新体会及超声心动图新发现
IF 2.7 4区 医学 Q3 VIROLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-15 DOI: 10.1016/j.virusres.2026.199690
Elham Mohamadyari , siros norozi , Iraj Ahmadi , anis Mohamadyari , hamed tavan
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引用次数: 0
PCBP2 inhibits antiviral innate immune responses via the MAVS-mediated signaling pathway in severe fever with thrombocytopenia syndrome PCBP2通过mavs介导的信号通路抑制发热伴血小板减少综合征的抗病毒先天免疫反应
IF 2.7 4区 医学 Q3 VIROLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-02 DOI: 10.1016/j.virusres.2026.199699
Xinyi Yu , Yan Dai , Xuewen Ji , Qinqin Pu , Ruonan Zhang , Mengqi Shi , Nannan Hu , Ke Jin , Jin Zhu , Jun Li

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high mortality and limited therapeutic options. Poly(rC)-binding protein 2 (PCBP2) is a multifunctional RNA-binding protein involved in post-transcriptional regulation and innate immune modulation. Although PCBP2 has been reported to negatively regulate antiviral signaling in other viral infections, its role in Dabie bandavirus (DBV) infection remains unclear.

Methods

Single-cell transcriptomic analysis was performed to characterize PCBP2 mRNA expression across immune cell populations in peripheral blood. PCBP2 expression levels were further examined in DBV-infected clinical samples, IFNAR⁻/⁻ mouse models, and THP-1 cells using quantitative RT-PCR, western blotting, and immunohistochemistry. THP-1 cells with plasmid-mediated PCBP2 overexpression or lentivirus-mediated PCBP2 knockdown were established to investigate the functional role of PCBP2. Activation of the RIG-I-like receptor (RLR) signaling pathway was evaluated by assessing key signaling molecules and downstream interferon responses. The impact of PCBP2 on DBV replication was determined by TCID50 assay, viral nucleoprotein (NP) expression, and immunofluorescence analysis.

Results

PCBP2 expression was significantly downregulated during DBV infection in clinical samples, animal models, and cell cultures, and reduced PCBP2 expression was associated with increased disease severity and unfavorable clinical outcomes. Functional analyses demonstrated that PCBP2 suppressed DBV-induced activation of type I interferon signaling and interferon-stimulated genes, including ISG12a and G1P3. Mechanistically, PCBP2 directly interacted with the mitochondrial antiviral signaling protein MAVS and promoted its K48-linked polyubiquitination, resulting in proteasome-dependent degradation and attenuation of the MAVS-TBK1-IRF3 signaling axis. Consistent with its immunosuppressive role, PCBP2 knockdown significantly reduced DBV replication, whereas PCBP2 overexpression enhanced viral replication in THP-1 cells.

Conclusions

These findings identify PCBP2 as a critical negative regulator of RLR-mediated antiviral signaling during DBV infection. By facilitating MAVS degradation and suppressing innate immune responses, PCBP2 promotes viral replication, providing new insights into DBV immune evasion mechanisms and highlighting PCBP2 as a potential host-directed therapeutic target for SFTS.
背景:发热伴血小板减少综合征(SFTS)是一种新兴的蜱传传染病,具有高死亡率和有限的治疗选择。Poly(rC)-binding protein 2 (PCBP2)是一种参与转录后调控和先天免疫调节的多功能rna结合蛋白。尽管有报道称PCBP2在其他病毒感染中负调控抗病毒信号,但其在大别河病毒(DBV)感染中的作用尚不清楚。方法:采用单细胞转录组学分析方法表征外周血免疫细胞群中PCBP2 mRNA的表达。PCBP2的表达水平在dbv感染的临床样本、IFNAR毒血症模型和THP-1细胞中进行了进一步的检测,方法包括定量RT-PCR、western blotting和免疫组织化学。建立质粒介导PCBP2过表达或慢病毒介导PCBP2敲低的THP-1细胞,研究PCBP2的功能作用。通过评估关键信号分子和下游干扰素反应来评估rig - i样受体(RLR)信号通路的激活。通过TCID50、病毒核蛋白(NP)表达和免疫荧光分析确定PCBP2对DBV复制的影响。结果:在临床样本、动物模型和细胞培养中,DBV感染期间PCBP2表达显著下调,PCBP2表达降低与疾病严重程度增加和不利的临床结果相关。功能分析表明,PCBP2抑制dbv诱导的I型干扰素信号和干扰素刺激基因(包括ISG12a和G1P3)的激活。机制上,PCBP2直接与线粒体抗病毒信号蛋白MAVS相互作用,促进其与k48相关的多泛素化,导致蛋白酶体依赖性的MAVS- tbk1 - irf3信号轴的降解和衰减。与其免疫抑制作用一致,PCBP2敲低可显著降低DBV复制,而PCBP2过表达可增强THP-1细胞中的病毒复制。结论:这些发现表明PCBP2是DBV感染期间rlr介导的抗病毒信号的关键负调控因子。PCBP2通过促进MAVS降解和抑制先天免疫反应,促进病毒复制,为DBV免疫逃避机制提供了新的见解,并突出了PCBP2作为SFTS潜在的宿主靶向治疗靶点。
{"title":"PCBP2 inhibits antiviral innate immune responses via the MAVS-mediated signaling pathway in severe fever with thrombocytopenia syndrome","authors":"Xinyi Yu ,&nbsp;Yan Dai ,&nbsp;Xuewen Ji ,&nbsp;Qinqin Pu ,&nbsp;Ruonan Zhang ,&nbsp;Mengqi Shi ,&nbsp;Nannan Hu ,&nbsp;Ke Jin ,&nbsp;Jin Zhu ,&nbsp;Jun Li","doi":"10.1016/j.virusres.2026.199699","DOIUrl":"10.1016/j.virusres.2026.199699","url":null,"abstract":"<div><h3>Background</h3><div>Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high mortality and limited therapeutic options. Poly(rC)-binding protein 2 (PCBP2) is a multifunctional RNA-binding protein involved in post-transcriptional regulation and innate immune modulation. Although PCBP2 has been reported to negatively regulate antiviral signaling in other viral infections, its role in Dabie bandavirus (DBV) infection remains unclear.</div></div><div><h3>Methods</h3><div>Single-cell transcriptomic analysis was performed to characterize PCBP2 mRNA expression across immune cell populations in peripheral blood. PCBP2 expression levels were further examined in DBV-infected clinical samples, IFNAR⁻/⁻ mouse models, and THP-1 cells using quantitative RT-PCR, western blotting, and immunohistochemistry. THP-1 cells with plasmid-mediated PCBP2 overexpression or lentivirus-mediated PCBP2 knockdown were established to investigate the functional role of PCBP2. Activation of the RIG-I-like receptor (RLR) signaling pathway was evaluated by assessing key signaling molecules and downstream interferon responses. The impact of PCBP2 on DBV replication was determined by TCID<sub>50</sub> assay, viral nucleoprotein (NP) expression, and immunofluorescence analysis.</div></div><div><h3>Results</h3><div>PCBP2 expression was significantly downregulated during DBV infection in clinical samples, animal models, and cell cultures, and reduced PCBP2 expression was associated with increased disease severity and unfavorable clinical outcomes. Functional analyses demonstrated that PCBP2 suppressed DBV-induced activation of type I interferon signaling and interferon-stimulated genes, including ISG12a and G1P3. Mechanistically, PCBP2 directly interacted with the mitochondrial antiviral signaling protein MAVS and promoted its K48-linked polyubiquitination, resulting in proteasome-dependent degradation and attenuation of the MAVS-TBK1-IRF3 signaling axis. Consistent with its immunosuppressive role, PCBP2 knockdown significantly reduced DBV replication, whereas PCBP2 overexpression enhanced viral replication in THP-1 cells.</div></div><div><h3>Conclusions</h3><div>These findings identify PCBP2 as a critical negative regulator of RLR-mediated antiviral signaling during DBV infection. By facilitating MAVS degradation and suppressing innate immune responses, PCBP2 promotes viral replication, providing new insights into DBV immune evasion mechanisms and highlighting PCBP2 as a potential host-directed therapeutic target for SFTS.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"365 ","pages":"Article 199699"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Engineered soluble truncated envelope proteins block bovine leukemia virus infection 工程可溶性截断包膜蛋白阻断牛白血病病毒感染。
IF 2.7 4区 医学 Q3 VIROLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-05 DOI: 10.1016/j.virusres.2026.199701
Nashon Wanjala , Ryusuke Matsumoto , Didik Pramono , Ariko Miyake , Kazuo Nishigaki
Bovine leukemia virus (BLV), a member of the delta retrovirus family, is transmitted horizontally among cows. BLV causes enzootic bovine leukosis and has great economic impact on the cattle industry. Recently, secretory-defective Env proteins (e.g., Refrex-1 and FeLIX) have been detected in domestic cats and shown to possess antiretroviral activity against gammaretroviruses via viral receptor interference. Therefore, we investigated whether BLV-derived molecules engineered similarly exhibit antiviral activity against BLV infection. We generated several proteins consisting of the BLV envelope surface unit (SU) region and signal peptide, without the transmembrane region, and tested their inhibitory effects on BLV infection. These artificial mutant Env-SU proteins were detected as secreted proteins in cultured cells. Colony formation and quantitative PCR assays revealed that the secreted Env-SU proteins exhibited an inhibitory effect on BLV infection. In conclusion, the engineered BLV Env-SU protein was found to effectively inhibit BLV infection, likely through a mechanism consistent with viral receptor interference and is expected to contribute to the development of infection-prevention methods against BLV.
牛白血病病毒(BLV)是三角洲逆转录病毒家族的一员,在牛之间水平传播。BLV引起地方性牛白血病,对养牛业有很大的经济影响。最近,在家猫中发现了分泌缺陷的Env蛋白(如refex -1和FeLIX),并显示出通过病毒受体干扰对γ -逆转录病毒具有抗逆转录病毒活性。因此,我们研究了BLV衍生分子是否对BLV感染表现出类似的抗病毒活性。我们制备了几种由BLV包膜表面单元(SU)区和信号肽组成的蛋白,不含跨膜区,并测试了它们对BLV感染的抑制作用。在培养细胞中检测到这些人工突变的Env-SU蛋白为分泌蛋白。集落形成和定量PCR分析表明,分泌的Env-SU蛋白对BLV感染有抑制作用。综上所述,该基因工程的BLV Env-SU蛋白可能通过与病毒受体干扰一致的机制有效抑制BLV感染,有望为BLV感染预防方法的发展做出贡献。
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引用次数: 0
NDV-GT wth hyperacute rejection in cancer therapy NDV-GT伴超急性排斥反应在癌症治疗中的应用。
IF 2.7 4区 医学 Q3 VIROLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-28 DOI: 10.1016/j.virusres.2026.199693
Zhiyu Li , Huiqin Chen , Zuhao Wang , Xiaodong Liu , Shugen Qu
Oncolytic viruses (OVs) represent a promising immunotherapy for cancer treatment, though their clinical application is often limited by systemic toxicity and low immunogenicity. To address this, we developed NDV-GT, a genetically engineered Newcastle disease virus that encodes porcine α-1,3-galactosyltransferase. These epitopes are recognized by pre-existing natural antibodies, triggering a hyperacute rejection response characterized by complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Furthermore, NDV-GT modulates the tumor microenvironment by promoting T-cell infiltration and cytokine secretion, converting immunologically “cold” tumors into “hot” ones. Mechanistically, the virus inhibits PI3K/AKT and NF-κB signaling pathways, inducing apoptosis and suppressing tumor proliferation. In a preliminary clinical study of 20 patients with advanced refractory carcinomas, NDV-GT achieved a 90.0% disease control rate with no serious adverse events, underscoring its potential as a novel, safe, and effective oncolytic agent that elicits robust antitumor immunity.
溶瘤病毒(OVs)是一种很有前途的癌症免疫疗法,但其临床应用往往受到全身毒性和低免疫原性的限制。为了解决这个问题,我们开发了NDV-GT,一种编码猪α-1,3-半乳糖转移酶的基因工程新城疫病毒。这些表位被预先存在的天然抗体识别,引发以补体依赖性细胞毒性(CDC)和抗体依赖性细胞毒性(ADCC)为特征的超急性排斥反应。此外,NDV-GT通过促进t细胞浸润和细胞因子分泌来调节肿瘤微环境,将免疫上的“冷”肿瘤转化为“热”肿瘤。机制上,该病毒抑制PI3K/AKT和NF-κB信号通路,诱导细胞凋亡,抑制肿瘤增殖。在一项针对20例晚期难治性癌患者的初步临床研究中,NDV-GT达到了90.0%的疾病控制率,无严重不良事件,强调了其作为一种新型、安全、有效的溶瘤药物的潜力,可引发强大的抗肿瘤免疫。
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引用次数: 0
RAB25 promotes hepatitis B virus-induced liver fibrosis progression through activation of the PI3K/AKT signaling pathway RAB25通过激活PI3K/AKT信号通路促进乙型肝炎病毒诱导的肝纤维化进展。
IF 2.7 4区 医学 Q3 VIROLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-04 DOI: 10.1016/j.virusres.2026.199698
Jing Liu, Bingjie Liu, Xia Xie, Xin Yang, Qiong Liu
Despite the clinical possibility of reducing hepatitis B virus (HBV) to almost undetectable levels through nucleotide analogs or interferon, the process of hepatic fibrosis in HBV hepatitis carriers perdures. This study will investigate the function of RAB25 in HBV-induced liver fibrosis and related mechanisms. In the study, the expression level of RAB25 was shown to be increased within liver fibrotic tissue samples in Gene Expression Omnibus (GEO) microarrays (GSE171294 and GSE84044) and clinical samples as well as in HBV-induced hepatic stellate cells (HSCs) activation. Silencing RAB25 inhibited HSCs activation induced by TGF-β1 and HBV-associated hepatocellular carcinoma cells HepG2.2.15, also significantly inhibited HSCs viability, proliferation, and migration and the expression levels of α-SMA, Collagen I, MMP2, and PCNA. However, the overexpression of RAB25 significantly promoted HBV-associated hepatocellular carcinoma cells and TGF-β1-induced HSCs activation. Mechanistically, silencing RAB25 in HSCs significantly repressed PI3K/AKT activation triggered by HBV-associated hepatocellular carcinoma cells. However, the overexpression of RAB25 notably promoted PI3K/AKT activation. In conclusion, silencing of RAB25 inhibits HBV-associated hepatocellular carcinoma cell-induced hepatic fibrosis by suppressing the PI3K/AKT signaling. RAB25 has been proven to be an underlying target for clinical treatment of HBV-associated liver fibrosis.
尽管临床有可能通过核苷酸类似物或干扰素将乙型肝炎病毒(HBV)降低到几乎无法检测到的水平,但HBV肝炎携带者的肝纤维化过程仍在继续。本研究将探讨RAB25在hbv诱导肝纤维化中的作用及其机制。在这项研究中,在基因表达综合(GEO)芯片(GSE171294和GSE84044)和临床样本中,以及在hbv诱导的肝星状细胞(hsc)活化中,RAB25的表达水平被证明在肝纤维化组织样本中升高。沉默RAB25抑制TGF-β1和hbv相关肝癌细胞HepG2.2.15诱导的hsc活化,显著抑制hsc的活力、增殖、迁移及α-SMA、Collagen I、MMP2、PCNA的表达水平。然而,RAB25过表达显著促进hbv相关肝癌细胞和TGF-β1诱导的hsc活化。在机制上,沉默hsc中的RAB25可显著抑制hbv相关肝癌细胞触发的PI3K/AKT激活。然而,RAB25的过表达显著促进了PI3K/AKT的激活。综上所述,RAB25的沉默通过抑制PI3K/AKT信号通路抑制hbv相关肝癌细胞诱导的肝纤维化。RAB25已被证明是hbv相关肝纤维化临床治疗的潜在靶点。
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引用次数: 0
Revelation of core promoter elements and bidirectional regulation of Geminivirus genes in Escherichia coli 大肠杆菌核心启动子元件的揭示及双病毒基因的双向调控。
IF 2.7 4区 医学 Q3 VIROLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-02 DOI: 10.1016/j.virusres.2026.199697
Hsiao-En Lin , Ying-Wen Huang , Yi-Chin Lai , Na-Sheng Lin , Yau-Heiu Hsu , Chung-Chi Hu
Several geminiviruses have been show to possess cross-kingdom gene expression capability. In addition, the intergenic region (IR) of geminivirus genomes is known to regulate the transcription of viral early genes (complementary-sense, C-sense) and late genes (virion-sense, V-sense) located in opposite directions in viral genomic DNAs. However, the underlying mechanism remained elusive. In this study, the transcriptional regulation activities in the IR of ageratum yellow vein virus isolate NT (AYVV-NT), a monopartite geminivirus, were characterized in Escherichia coli, by using a promoter-trapping system. A functional bidirectional promoter core and regulatory elements for C- and V-sense genes were identified in the IR of AYVV-NT. Quantitative analyses revealed differences in promoter activity in various E. coli strains, suggesting that promoter regulation is strain-dependent and influenced by bacterial transcription factors. These findings provide insights into how plant-infecting geminiviruses may regulate gene expression in prokaryotic environments and highlight the potential applications of such viral regulatory elements in bacterial expression systems.
一些双病毒已被证明具有跨界基因表达能力。此外,已知双病毒基因组的基因间区(IR)调节病毒基因组dna中位于相反方向的病毒早期基因(互补感,c感)和晚期基因(病毒感,v感)的转录。然而,潜在的机制仍然难以捉摸。本研究利用启动子诱捕系统,在大肠杆菌中研究了一种单单双胞病毒ageratum yellow vein virus分离物NT (AYVV-NT)在IR中的转录调控活性。在AYVV-NT的IR中发现了一个功能性的双向启动子核心和C-和V-sense基因的调控元件。定量分析显示,不同大肠杆菌菌株的启动子活性存在差异,表明启动子的调控是菌株依赖的,受细菌转录因子的影响。这些发现为了解侵染植物的双病毒如何在原核环境中调控基因表达提供了见解,并突出了此类病毒调控元件在细菌表达系统中的潜在应用。
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引用次数: 0
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Virus research
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