Virus research最新文献_第10页

A systematic review of T cell epitopes defined from the proteome of human immunodeficiency virus 从人类免疫缺陷病毒蛋白质组中确定的T细胞表位的系统综述

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2025-08-01 Epub Date: 2025-06-23 DOI: 10.1016/j.virusres.2025.199602

Yan Ding , Ling Huang , Yandan Wu , Jialai Yan

Background

Human immunodeficiency virus (HIV) persists as a formidable and far - reaching threat without a cure. T cells are crucial for antiviral immunity and pathology in HIV patients, with specific T cell epitopes potentially key to effective therapies and HIV cure methods.

Methods

Identifying sufficient T-cell epitopes within the HIV proteome holds great significance. It can not only substantially accelerate the development of T-cell epitope-based vaccines but also enable a highly precise evaluation of the host's HIV-specific cellular immunity. This research provides an overview of functionally verified T-cell epitopes derived from HIV antigens, the human leukocyte antigen (HLA) alleles, as well as the screening and identification strategies.

Results

Totally, 239 and 82 epitopes have been verified for CD8⁺ T-cell and CD4⁺ T-cell respectively by functional experiments. The majority are presented by various HLA supertypes, such as HLA-B35, B5301, A6802 or A0201, and DRB1 molecules. Furthermore, 74 % of the epitopes for CD8⁺T-cell belong to Gag, Pol, as well as Nef Protein while 68 % of the CD4⁺ T-cell epitopes originate from Gag protein. Antigenic peptides of HIV-1 subtypes A/B/C/D/CRF01_AE account for 11.43 %, 58.26 %, 21.69 %, 4.96 %, and 3.65 %, respectively.

Conclusions

The 321 T-cell epitope repertoires of HIV encompass the HLA polymorphisms of the main populations and subtypes in a particular geographical area. These epitope catalogs provide strong support for researching therapeutic vaccines, specific T-cell detection, and the interaction mechanism between HIV and the immune system. However, the limitations of the identified T-cell epitope library, the polymorphism of HLA molecules, and the high mutation rate of HIV require more research to cover the entire HIV proteome and the comprehensive landscape of T-cell epitopes in global patients.

人类免疫缺陷病毒（HIV）一直是一种无法治愈的可怕而深远的威胁。T细胞对HIV患者的抗病毒免疫和病理至关重要，特定的T细胞表位可能是有效治疗和HIV治愈方法的关键。方法在HIV蛋白组中发现足够的t细胞表位具有重要意义。它不仅可以大大加速基于t细胞表位的疫苗的开发，而且可以高度精确地评估宿主的hiv特异性细胞免疫。本研究概述了功能性验证的源自HIV抗原的t细胞表位，人类白细胞抗原（HLA）等位基因，以及筛选和鉴定策略。结果CD8+ t细胞和CD4+ t细胞经功能实验分别鉴定出239个和82个表位。大多数是各种HLA超型，如HLA- b35、B5301、A6802或A0201和DRB1分子。此外，CD8+ t细胞74%的表位属于Gag、Pol和Nef蛋白，而CD4+ t细胞68%的表位来自Gag蛋白。HIV-1 A/B/C/D/CRF01_AE亚型抗原肽分别占11.43%、58.26%、21.69%、4.96%和3.65%。结论321个HIV t细胞表位库包含了特定地理区域主要人群和亚型的HLA多态性。这些表位目录为研究治疗性疫苗、特异性t细胞检测以及HIV与免疫系统的相互作用机制提供了强有力的支持。然而，由于已鉴定的t细胞表位文库的局限性、HLA分子的多态性以及HIV的高突变率，需要更多的研究来覆盖整个HIV蛋白质组和全球患者t细胞表位的综合景观。

{"title":"A systematic review of T cell epitopes defined from the proteome of human immunodeficiency virus","authors":"Yan Ding , Ling Huang , Yandan Wu , Jialai Yan","doi":"10.1016/j.virusres.2025.199602","DOIUrl":"10.1016/j.virusres.2025.199602","url":null,"abstract":"<div><h3>Background</h3><div>Human immunodeficiency virus (HIV) persists as a formidable and far - reaching threat without a cure. T cells are crucial for antiviral immunity and pathology in HIV patients, with specific T cell epitopes potentially key to effective therapies and HIV cure methods.</div></div><div><h3>Methods</h3><div>Identifying sufficient T-cell epitopes within the HIV proteome holds great significance. It can not only substantially accelerate the development of T-cell epitope-based vaccines but also enable a highly precise evaluation of the host's HIV-specific cellular immunity. This research provides an overview of functionally verified T-cell epitopes derived from HIV antigens, the human leukocyte antigen (HLA) alleles, as well as the screening and identification strategies.</div></div><div><h3>Results</h3><div>Totally, 239 and 82 epitopes have been verified for CD8<sup>+</sup> T-cell and CD4<sup>+</sup> T-cell respectively by functional experiments. The majority are presented by various HLA supertypes, such as HLA-B35, B5301, A6802 or A0201, and DRB1 molecules. Furthermore, 74 % of the epitopes for CD8<sup>+</sup>T-cell belong to Gag, Pol, as well as Nef Protein while 68 % of the CD4<sup>+</sup> T-cell epitopes originate from Gag protein. Antigenic peptides of HIV-1 subtypes A/B/C/D/CRF01_AE account for 11.43 %, 58.26 %, 21.69 %, 4.96 %, and 3.65 %, respectively.</div></div><div><h3>Conclusions</h3><div>The 321 T-cell epitope repertoires of HIV encompass the HLA polymorphisms of the main populations and subtypes in a particular geographical area. These epitope catalogs provide strong support for researching therapeutic vaccines, specific T-cell detection, and the interaction mechanism between HIV and the immune system. However, the limitations of the identified T-cell epitope library, the polymorphism of HLA molecules, and the high mutation rate of HIV require more research to cover the entire HIV proteome and the comprehensive landscape of T-cell epitopes in global patients.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"358 ","pages":"Article 199602"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489404","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

Characterization of antigenically dominant regions in the hemagglutinin protein of B/victoria-lineage influenza B virus using monoclonal antibody escape mutants 利用单克隆抗体逃逸突变体研究B/维多利亚乙型流感病毒血凝素蛋白抗原优势区

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2025-08-01 Epub Date: 2025-06-14 DOI: 10.1016/j.virusres.2025.199598

Yoko Matsuzaki , Kanetsu Sugawara , Yoko Kadowaki , Yuko Kidoguchi , Yoshitaka Shimotai , Katsumi Mizuta

As of 2024, B/Victoria-lineage strains have emerged as the predominant influenza B viruses globally. To elucidate the antigenic regions responsible for variation within this lineage, three monoclonal antibodies (MAbs) targeting the hemagglutinin (HA) protein were employed to generate escape mutants of the B/Victoria strain B/Aichi/20/99, which was isolated approximately 10 years after the B/Victoria and B/Yamagata lineages began cocirculating. A total of 45 escape mutants were obtained. Sequencing of their HA genes identified six amino acid substitutions at four sites within two key antigenic regions—the 160-loop and 190-helix—specifically, N165Y, N165S, K167R, and an asparagine insertion between residues 164 and 165 in the 160-loop; and K203R and K203N in the 190-helix (numbering is based on the B/Brisbane/60/2008 HA sequence). Hemagglutination inhibition (HI) assays revealed that two MAbs affected binding of both mutants with mutations in the 160-loop and those with a mutation at residue 203. Mutations in the 160-loop did not affect reactivity with antiserum against the parental B/Aichi/20/99 strain, whereas K203N substitution reduced antiserum reactivity, indicating the antigenic importance of this residue. Further HI analyses using eight B/Victoria lineage strains isolated between 1997 and 2021 showed that all three MAbs lost reactivity with strains isolated after 2016, while the antiserum demonstrated reduced reactivity. Notably, the current vaccine strain, B/Austria/1359417/2021, which harbors substitutions at positions 150 and 203, also exhibited diminished reactivity. These findings suggest that both the 150-loop and 190-helix constitute antigenically dominant sites that contribute to immune escape and the emergence of drift variants within the B/Victoria-lineage.

截至2024年，B/维多利亚谱系毒株已成为全球主要的乙型流感病毒。为了阐明该谱系变异的抗原区域，利用3种靶向血凝素（HA）蛋白的单克隆抗体（mab）产生B/Victoria菌株B/Aichi/20/99的逃逸突变体，该突变体是在B/Victoria和B/Yamagata谱系开始共循环约10年后分离出来的。共获得45个逃逸突变体。他们的HA基因测序在两个关键抗原区域（160环和190螺旋）的四个位点上发现了六个氨基酸替换，特别是N165Y， N165S, K167R，以及160环中164和165残基之间的天冬酰胺插入；和K203R和K203N在190螺旋（编号基于B/Brisbane/60/2008 HA序列）。血球凝集抑制（HI）实验显示，两种单克隆抗体影响了160环突变体和203环突变体的结合。160环突变不影响抗血清对亲本B/爱知/20/99菌株的反应性，而K203N取代降低了抗血清反应性，表明该残基具有重要的抗原性。对1997年至2021年间分离的8株B/Victoria谱系菌株进行的进一步HI分析显示，所有3种单克隆抗体与2016年之后分离的菌株都失去了反应性，而抗血清的反应性降低。值得注意的是，目前的疫苗株B/Austria/1359417/2021在150和203位上有取代，反应性也有所下降。这些发现表明，在B/维多利亚谱系中，150环和190螺旋构成抗原优势位点，有助于免疫逃逸和漂移变异的出现。

{"title":"Characterization of antigenically dominant regions in the hemagglutinin protein of B/victoria-lineage influenza B virus using monoclonal antibody escape mutants","authors":"Yoko Matsuzaki , Kanetsu Sugawara , Yoko Kadowaki , Yuko Kidoguchi , Yoshitaka Shimotai , Katsumi Mizuta","doi":"10.1016/j.virusres.2025.199598","DOIUrl":"10.1016/j.virusres.2025.199598","url":null,"abstract":"<div><div>As of 2024, B/Victoria-lineage strains have emerged as the predominant influenza B viruses globally. To elucidate the antigenic regions responsible for variation within this lineage, three monoclonal antibodies (MAbs) targeting the hemagglutinin (HA) protein were employed to generate escape mutants of the B/Victoria strain B/Aichi/20/99, which was isolated approximately 10 years after the B/Victoria and B/Yamagata lineages began cocirculating. A total of 45 escape mutants were obtained. Sequencing of their HA genes identified six amino acid substitutions at four sites within two key antigenic regions—the 160-loop and 190-helix—specifically, N165Y, N165S, K167R, and an asparagine insertion between residues 164 and 165 in the 160-loop; and K203R and K203N in the 190-helix (numbering is based on the B/Brisbane/60/2008 HA sequence). Hemagglutination inhibition (HI) assays revealed that two MAbs affected binding of both mutants with mutations in the 160-loop and those with a mutation at residue 203. Mutations in the 160-loop did not affect reactivity with antiserum against the parental B/Aichi/20/99 strain, whereas K203N substitution reduced antiserum reactivity, indicating the antigenic importance of this residue. Further HI analyses using eight B/Victoria lineage strains isolated between 1997 and 2021 showed that all three MAbs lost reactivity with strains isolated after 2016, while the antiserum demonstrated reduced reactivity. Notably, the current vaccine strain, B/Austria/1359417/2021, which harbors substitutions at positions 150 and 203, also exhibited diminished reactivity. These findings suggest that both the 150-loop and 190-helix constitute antigenically dominant sites that contribute to immune escape and the emergence of drift variants within the B/Victoria-lineage.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"358 ","pages":"Article 199598"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310501","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

Enterovirus 71 structural viral protein 1 promotes the expression of PMP22 through m6A modification in mouse Schwann cells 肠病毒71结构病毒蛋白1通过m6A修饰促进小鼠雪旺细胞PMP22的表达。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2025-08-01 Epub Date: 2025-06-04 DOI: 10.1016/j.virusres.2025.199590

Qiuyan Peng , Guangming Liu , Danping Zhu , Suyun Li , Sida Yang , Peiqing Li , Yingxian Yin , Dandan Hu

Purpose

Enterovirus 71 (EV71) is one of the enteroviruses that causes hand-foot-and-mouth disease (HFMD). This study aims to investigate the role of EV71 structural viral protein 1 (VP1) in mouse Schwann cells.

Methods

An EV71 VP1-expressing vector was generated and transfected into mouse Schwann cells (MSCs). Small interfering RNAs against methyltransferase-like protein 14 (METTL14) and YTH N⁶-Methyladenosine RNA Binding Protein 1 (YTHDF1) were used to knock down the expressions of METTL14 and YTHDF1 in MSCs to investigate their roles in peripheral myelin protein 22 (PMP22) expression. Real-time PCR and Western blot analysis were performed to determine the expressions of PMP22 and m⁶A modification-associated proteins.

Results

EV71-VP1 over-expression significantly increased the expressions of transmethylase METTL3/14 and m⁶A methylation recognition protein YTHDC1 and YTHDF1/2/3 in MSCs. On the contrary, the level of demethylase FTO, but not ALKBH5, was obviously decreased in VP1-over-expressed MSCs. Furthermore, 3-DZA inhibited expressions of METTL3/14 and YTHDF1/2 in VP1-over-expressed MSCs, indicating METTL3/14 and YTHDF1/2 were the key m⁶A-modification-related genes regulated by VP1. In addition, deficiency of METTL14 or YTHDF1 contracted the up-regulation of PMP22 induced by VP1 overexpression in MSCs.

Conclusions

VP1 up-regulated PMP22 via m6A modification in MSCs, which were mainly affected by METTL14 and YTHDF1.

目的：肠病毒71 （EV71）是引起手足口病（手足口病）的肠道病毒之一。本研究旨在探讨EV71结构病毒蛋白1 （VP1）在小鼠雪旺细胞中的作用。方法：制备EV71表达载体，转染小鼠雪旺细胞（MSCs）。利用靶向甲基转移酶样蛋白14 （METTL14）和YTH n6 -甲基腺苷RNA结合蛋白1 （YTHDF1）的小干扰RNA敲低MSCs中METTL14和YTHDF1的表达，研究其在外周血髓磷脂蛋白22 （PMP22）表达中的作用。采用Real-time PCR和Western blot检测PMP22和m6A修饰相关蛋白的表达。结果：EV71-VP1过表达显著增加MSCs中转甲基化酶METTL3/14和m6A甲基化识别蛋白YTHDC1和YTHDF1/2/3的表达。相反，在vp1过表达的MSCs中，去甲基化酶FTO水平明显降低，而ALKBH5水平不明显降低。此外，3-DZA抑制过表达VP1的MSCs中METTL3/14和YTHDF1/2的表达，说明METTL3/14和YTHDF1/2是VP1调控m6a修饰的关键基因。此外，METTL14或YTHDF1的缺失使MSCs中VP1过表达诱导的PMP22上调。结论：VP1在MSCs中通过m6A修饰上调PMP22，主要受METTL14和YTHDF1的影响。

{"title":"Enterovirus 71 structural viral protein 1 promotes the expression of PMP22 through m6A modification in mouse Schwann cells","authors":"Qiuyan Peng , Guangming Liu , Danping Zhu , Suyun Li , Sida Yang , Peiqing Li , Yingxian Yin , Dandan Hu","doi":"10.1016/j.virusres.2025.199590","DOIUrl":"10.1016/j.virusres.2025.199590","url":null,"abstract":"<div><h3>Purpose</h3><div>Enterovirus 71 (EV71) is one of the enteroviruses that causes hand-foot-and-mouth disease (HFMD). This study aims to investigate the role of EV71 structural viral protein 1 (VP1) in mouse Schwann cells.</div></div><div><h3>Methods</h3><div>An EV71 VP1-expressing vector was generated and transfected into mouse Schwann cells (MSCs). Small interfering RNAs against methyltransferase-like protein 14 (METTL14) and YTH N<sup>6</sup>-Methyladenosine RNA Binding Protein 1 (YTHDF1) were used to knock down the expressions of METTL14 and YTHDF1 in MSCs to investigate their roles in peripheral myelin protein 22 (PMP22) expression. Real-time PCR and Western blot analysis were performed to determine the expressions of PMP22 and m<sup>6</sup>A modification-associated proteins.</div></div><div><h3>Results</h3><div>EV71-VP1 over-expression significantly increased the expressions of transmethylase METTL3/14 and m<sup>6</sup>A methylation recognition protein YTHDC1 and YTHDF1/2/3 in MSCs. On the contrary, the level of demethylase FTO, but not ALKBH5, was obviously decreased in VP1-over-expressed MSCs. Furthermore, 3-DZA inhibited expressions of METTL3/14 and YTHDF1/2 in VP1-over-expressed MSCs, indicating METTL3/14 and YTHDF1/2 were the key m<sup>6</sup>A-modification-related genes regulated by VP1. In addition, deficiency of METTL14 or YTHDF1 contracted the up-regulation of PMP22 induced by VP1 overexpression in MSCs.</div></div><div><h3>Conclusions</h3><div>VP1 up-regulated PMP22 via m6A modification in MSCs, which were mainly affected by METTL14 and YTHDF1.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"358 ","pages":"Article 199590"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249825","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

Evolutionary characterization and pathogenicity of a porcine G9P[23] rotavirus with gene segments linked to canine and giant panda strains 猪G9P[23]轮状病毒与犬和大熊猫毒株相关基因片段的进化特征和致病性

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2025-08-01 Epub Date: 2025-06-15 DOI: 10.1016/j.virusres.2025.199600

Xi Li , Jingjing Wang , Yuankui Zhang , Yarong Zhao , Wenjun Liu , Yanli Shi

Porcine rotavirus A (RVA) has emerged as an increasingly consequential zoonotic pathogen, causing severe intestinal disorders across diverse mammalian species, including humans. During of an outbreak that struck nursing piglets with diarrhea, a porcine G9P[23] rotavirus, named as RVA/Pig-wt/China/ZJ03/2022/G9P[23] (hereafter referred to as ZJ03), was identified. To further elucidate the evolutionary diversity of ZJ03, a comprehensive analysis of all genome segments was conducted. The genome constellation was identified as G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Nucleotide sequence identity and phylogenetic analyses indicated that the VP3 and NSP1 genes of ZJ03 are most closely related to the corresponding genes of the giant panda strain and the dog strain, respectively, showing the highest homology at 95.73 % identity and 94.64 %. The remaining genes demonstrated the most intimate relationship with porcine strains. Their highest homology levels ranged from 95.98 % to 99.49 % similarity. Therefore, evidence suggests interspecies transmission and genetic reassortment events between porcine, canine, and giant panda rotavirus strains. To evaluate the pathogenicity of ZJ03 strain, we experimentally infected 3-day-old piglets oral inoculation with the PoRV ZJ03 strain at a dose of 2 × 10^5.5 TCID₅₀/ml per piglet. The infection resulted in severe diarrhea in all piglets, which occurred at 48 h post-infection (hpi), accompanied by sustained viral shedding and characteristic small intestinal villous atrophy, indicating significant damage to the intestinal epithelium. In vitro, ZJ03 exhibited efficient replication kinetics in MA104 cells, reaching peak titers of 10^9.25 TCID₅₀/mL at 36 h post-infection. This study reports the first documented case of a novel porcine G9P[23] rotavirus with gene segments linked to canine and giant panda strains in mainland China, characterized by high viral titer and virulence. The findings highlight the emergence of a previously unrecorded RVA strain with significant virological and ecological implications.

猪轮状病毒A （RVA）已成为一种越来越重要的人畜共患病原体，在包括人类在内的多种哺乳动物物种中引起严重的肠道疾病。在一次以腹泻感染哺乳仔猪的疫情中，发现了一种猪G9P[23]轮状病毒，命名为RVA/Pig-wt/China/ZJ03/2022/G9P[23]（以下简称ZJ03）。为了进一步阐明ZJ03的进化多样性，我们对其所有基因组片段进行了综合分析。基因组群鉴定为G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1。核苷酸序列鉴定和系统发育分析表明，ZJ03的VP3和NSP1基因分别与大熊猫品系和犬品系的对应基因亲缘关系最为密切，同源性最高，分别为95.73%和94.64%。其余基因与猪株的关系最为密切。最高同源度为95.98% ~ 99.49%。因此，有证据表明猪、犬和大熊猫轮状病毒毒株之间存在种间传播和基因重组事件。为了评估ZJ03菌株的致病性，我们实验用2 × 10^5.5 TCID50/ml /头仔猪口服接种ZJ03菌株感染3日龄仔猪。所有仔猪在感染后48小时出现严重腹泻，并伴有持续的病毒脱落和特征性的小肠绒毛萎缩，表明肠上皮受到严重损伤。在体外，ZJ03在MA104细胞中表现出高效的复制动力学，在感染后36小时达到峰值滴度10^9.25 TCID50/mL。本研究报告了中国大陆首次记录的新型猪G9P[23]轮状病毒，其基因片段与犬和大熊猫毒株相关，具有高病毒滴度和毒力的特点。这些发现强调了一种以前未记录的RVA菌株的出现，具有重要的病毒学和生态学意义。

{"title":"Evolutionary characterization and pathogenicity of a porcine G9P[23] rotavirus with gene segments linked to canine and giant panda strains","authors":"Xi Li , Jingjing Wang , Yuankui Zhang , Yarong Zhao , Wenjun Liu , Yanli Shi","doi":"10.1016/j.virusres.2025.199600","DOIUrl":"10.1016/j.virusres.2025.199600","url":null,"abstract":"<div><div>Porcine rotavirus A (RVA) has emerged as an increasingly consequential zoonotic pathogen, causing severe intestinal disorders across diverse mammalian species, including humans. During of an outbreak that struck nursing piglets with diarrhea, a porcine G9P[23] rotavirus, named as RVA/Pig-wt/China/ZJ03/2022/G9P[23] (hereafter referred to as ZJ03), was identified. To further elucidate the evolutionary diversity of ZJ03, a comprehensive analysis of all genome segments was conducted. The genome constellation was identified as G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Nucleotide sequence identity and phylogenetic analyses indicated that the VP3 and NSP1 genes of ZJ03 are most closely related to the corresponding genes of the giant panda strain and the dog strain, respectively, showing the highest homology at 95.73 % identity and 94.64 %. The remaining genes demonstrated the most intimate relationship with porcine strains. Their highest homology levels ranged from 95.98 % to 99.49 % similarity. Therefore, evidence suggests interspecies transmission and genetic reassortment events between porcine, canine, and giant panda rotavirus strains. To evaluate the pathogenicity of ZJ03 strain, we experimentally infected 3-day-old piglets oral inoculation with the PoRV ZJ03 strain at a dose of 2 × 10^5.5 TCID<sub>50</sub>/ml per piglet. The infection resulted in severe diarrhea in all piglets, which occurred at 48 h post-infection (hpi), accompanied by sustained viral shedding and characteristic small intestinal villous atrophy, indicating significant damage to the intestinal epithelium. In vitro, ZJ03 exhibited efficient replication kinetics in MA104 cells, reaching peak titers of 10^9.25 TCID<sub>50</sub>/mL at 36 h post-infection. This study reports the first documented case of a novel porcine G9P[23] rotavirus with gene segments linked to canine and giant panda strains in mainland China, characterized by high viral titer and virulence. The findings highlight the emergence of a previously unrecorded RVA strain with significant virological and ecological implications.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"358 ","pages":"Article 199600"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318045","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

Preparation and pharmacokinetic evaluation of Staphylococcus phage COP-80B for treatment of periprosthetic joint infections in a mouse model 噬菌体葡萄球菌COP-80B治疗小鼠假体周围关节感染的制备及药动学评价

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2025-07-01 Epub Date: 2025-05-31 DOI: 10.1016/j.virusres.2025.199592

Vida Štilec , Monika Marušić , Nika Janež , Urban Bezeljak , Lucija Rebula , Maja Leskovec , Rihard Trebše , Simon Horvat , Matjaž Peterka

Phage therapy has recently attracted significant attention as a potential treatment for periprosthetic joint infections, yielding promising outcomes in several compassionate use cases. The absence of standardized treatment protocols is partly attributable to insufficient pharmacokinetic data regarding relevant phage administration routes and dosages. Another neglected aspect is the scalable manufacturing of pharmaceutical-grade phage preparations for preclinical testing. In this study, we address both challenges and present a scalable phage production process for the Staphylococcus epidermidis-specific phage COP-80B We prepared a highly purified phage suspension, as verified through qPCR, HPLC, NTA and short-read sequencing, which was used in a preclinical pharmacokinetic study in an uninfected mice model. Using a plaque assay, we determined phage concentrations in mouse organs over time after intraperitoneal and intra-articular application of 10⁹ phages. Intra-articularly administered phages persisted in the periarticular tissue for several days, entered the systemic circulation and were subsequently cleared from the liver and spleen. Conversely, intraperitoneally administered phages did not reach the intra-articular space. No adverse events and no changes in hematological parameters were observed in mice after phage application by either route, confirming the safety of a single-dose application. Our results emphasize the importance of local phage administration for sustained presence in periarticular tissue and provide valuable pharmacokinetic data to support the development of optimized treatment protocols for periprosthetic joint infections.

噬菌体治疗作为一种潜在的治疗假体周围关节感染的方法最近引起了人们的极大关注，在一些富有同情心的用例中产生了有希望的结果。缺乏标准化治疗方案的部分原因是有关噬菌体给药途径和剂量的药代动力学数据不足。另一个被忽视的方面是用于临床前测试的药物级噬菌体制剂的规模化生产。在这项研究中，我们解决了这两个挑战，并提出了一种可扩展的表皮葡萄球菌特异性噬菌体COP-80B的噬菌体生产工艺。我们制备了高度纯化的噬菌体悬浮液，经qPCR、HPLC、NTA和短读测序验证，用于未感染小鼠模型的临床前药代动力学研究。使用斑块测定法，我们在腹腔和关节内应用109个噬菌体后，测定了小鼠器官中随时间的噬菌体浓度。关节内给药的噬菌体在关节周围组织中持续数天，进入体循环，随后从肝脏和脾脏中清除。相反，腹腔注射噬菌体不能到达关节内间隙。两种给药方式均未观察到小鼠的不良反应和血液学参数变化，证实了单剂量给药的安全性。我们的研究结果强调了局部噬菌体给药对于关节周围组织持续存在的重要性，并提供了有价值的药代动力学数据，以支持假体周围关节感染的优化治疗方案的发展。

{"title":"Preparation and pharmacokinetic evaluation of Staphylococcus phage COP-80B for treatment of periprosthetic joint infections in a mouse model","authors":"Vida Štilec , Monika Marušić , Nika Janež , Urban Bezeljak , Lucija Rebula , Maja Leskovec , Rihard Trebše , Simon Horvat , Matjaž Peterka","doi":"10.1016/j.virusres.2025.199592","DOIUrl":"10.1016/j.virusres.2025.199592","url":null,"abstract":"<div><div>Phage therapy has recently attracted significant attention as a potential treatment for periprosthetic joint infections, yielding promising outcomes in several compassionate use cases. The absence of standardized treatment protocols is partly attributable to insufficient pharmacokinetic data regarding relevant phage administration routes and dosages. Another neglected aspect is the scalable manufacturing of pharmaceutical-grade phage preparations for preclinical testing. In this study, we address both challenges and present a scalable phage production process for the <em>Staphylococcus epidermidis</em>-specific phage COP-80B We prepared a highly purified phage suspension, as verified through qPCR, HPLC, NTA and short-read sequencing, which was used in a preclinical pharmacokinetic study in an uninfected mice model. Using a plaque assay, we determined phage concentrations in mouse organs over time after intraperitoneal and intra-articular application of 10<sup>9</sup> phages. Intra-articularly administered phages persisted in the periarticular tissue for several days, entered the systemic circulation and were subsequently cleared from the liver and spleen. Conversely, intraperitoneally administered phages did not reach the intra-articular space. No adverse events and no changes in hematological parameters were observed in mice after phage application by either route, confirming the safety of a single-dose application. Our results emphasize the importance of local phage administration for sustained presence in periarticular tissue and provide valuable pharmacokinetic data to support the development of optimized treatment protocols for periprosthetic joint infections.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199592"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209644","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

Inhibition of Semliki Forest virus replication with long double-stranded RNA in Aedes albopictus cells 长双链RNA抑制塞姆利基森林病毒在白纹伊蚊细胞中的复制。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2025-07-01 Epub Date: 2025-05-17 DOI: 10.1016/j.virusres.2025.199584

Alejandra Centurión , Bodunrin Omokungbe , Sabrina Stiehler , Andreas Vilcinskas , Kornelia Hardes

Arthropod-borne viruses represent an increasing threat to the global health system, requiring the development of novel and sustainable control strategies to reduce the risk of arboviral infections. RNA interference (RNAi) offers a potential approach to directly prevent viral replication within vectors due to its specificity in gene silencing. In this study, we evaluated the efficacy of long double-stranded RNAs (dsRNAs) targeting six regions of the Semliki Forest virus (SFV) genome in Aedes albopictus U4.4 cells. The antiviral efficiency of dsRNA alone is low, therefore we evaluated its use after complexing with the K4 Transfection System (K4). A cytotoxicity assay based on ATP quantification showed that both uncomplexed and complexed dsRNA had no cytotoxic effects on U4.4 cells at a concentration up to 2 ng/µL. Complexed dsRNA achieved higher antiviral efficacy, significantly reducing viral replication compared to uncomplexed dsRNA. We found that complexed dsRNA retained its antiviral activity when challenged with SFV up to 72 h post-transfection. Among our synthesized dsRNA constructs, nsP4-dsRNA in complex with K4 led to an 80 % reduction in viral replication at 72 h post-infection at 0.5 ng/µL. Using RT-qPCR, we confirmed a significant 32.2 % reduction of nsP4 mRNA after transfection of complexed nsP4-dsRNA. Dose response assays showed that complexed dsRNAs with a concentration of 0.5 ng/µL are effective for viral reduction. Our results highlight the importance of efficient dsRNA delivery and selection of critical viral targets, such as nsP4, for successful RNAi-mediated viral suppression. This work elucidates the potential of dsRNAs to target Semliki Forest virus replication, highlighting viral gene targeting as a viable strategy for RNAi-based suppression of arboviral replication.

节肢动物传播的病毒对全球卫生系统构成越来越大的威胁，需要制定新的和可持续的控制战略，以减少虫媒病毒感染的风险。RNA干扰（RNAi）由于其在基因沉默中的特异性，为直接阻止病毒在载体内复制提供了一种潜在的方法。在这项研究中，我们评估了针对白纹伊蚊U4.4细胞中塞姆利基森林病毒（SFV）基因组6个区域的长双链rna （dsRNAs）的有效性。单独使用dsRNA的抗病毒效率较低，因此我们评估了其与K4转染系统（K4）络合后的使用效果。基于ATP定量的细胞毒性实验表明，在浓度高达2 ng/µL的情况下，未络合和络合的dsRNA对U4.4细胞没有细胞毒性作用。与未复配的dsRNA相比，复配的dsRNA具有更高的抗病毒功效，显著减少了病毒复制。我们发现，在转染后72小时，当SFV攻击时，复合物dsRNA仍保持其抗病毒活性。在我们合成的dsRNA结构中，nsP4-dsRNA与K4复合物在0.5 ng/µL的浓度下，在感染后72小时导致病毒复制减少80%。通过RT-qPCR，我们证实了nsP4- dsrna复合物转染后nsP4 mRNA显著减少32.2%。剂量反应实验表明，浓度为0.5 ng/µL的复合dsRNAs对病毒还原有效。我们的研究结果强调了有效的dsRNA传递和选择关键病毒靶点（如nsP4）对于成功的rnai介导的病毒抑制的重要性。这项工作阐明了dsRNAs靶向塞姆利基森林病毒复制的潜力，强调了病毒基因靶向是一种基于rnai抑制虫载病毒复制的可行策略。

{"title":"Inhibition of Semliki Forest virus replication with long double-stranded RNA in Aedes albopictus cells","authors":"Alejandra Centurión , Bodunrin Omokungbe , Sabrina Stiehler , Andreas Vilcinskas , Kornelia Hardes","doi":"10.1016/j.virusres.2025.199584","DOIUrl":"10.1016/j.virusres.2025.199584","url":null,"abstract":"<div><div>Arthropod-borne viruses represent an increasing threat to the global health system, requiring the development of novel and sustainable control strategies to reduce the risk of arboviral infections. RNA interference (RNAi) offers a potential approach to directly prevent viral replication within vectors due to its specificity in gene silencing. In this study, we evaluated the efficacy of long double-stranded RNAs (dsRNAs) targeting six regions of the Semliki Forest virus (SFV) genome in <em>Aedes albopictus</em> U4.4 cells. The antiviral efficiency of dsRNA alone is low, therefore we evaluated its use after complexing with the K4 Transfection System (K4). A cytotoxicity assay based on ATP quantification showed that both uncomplexed and complexed dsRNA had no cytotoxic effects on U4.4 cells at a concentration up to 2 ng/µL. Complexed dsRNA achieved higher antiviral efficacy, significantly reducing viral replication compared to uncomplexed dsRNA. We found that complexed dsRNA retained its antiviral activity when challenged with SFV up to 72 h post-transfection. Among our synthesized dsRNA constructs, nsP4-dsRNA in complex with K4 led to an 80 % reduction in viral replication at 72 h post-infection at 0.5 ng/µL. Using RT-qPCR, we confirmed a significant 32.2 % reduction of nsP4 mRNA after transfection of complexed nsP4-dsRNA. Dose response assays showed that complexed dsRNAs with a concentration of 0.5 ng/µL are effective for viral reduction. Our results highlight the importance of efficient dsRNA delivery and selection of critical viral targets, such as nsP4, for successful RNAi-mediated viral suppression. This work elucidates the potential of dsRNAs to target Semliki Forest virus replication, highlighting viral gene targeting as a viable strategy for RNAi-based suppression of arboviral replication.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199584"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102633","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

The global prevalence of co-occurrence of Sjögren syndrome and Hepatitis C virus infection: A systematic review and meta-analysis Sjögren综合征和丙型肝炎病毒感染共发的全球患病率：一项系统回顾和荟萃分析

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2025-07-01 Epub Date: 2025-05-13 DOI: 10.1016/j.virusres.2025.199585

Nasir Arefinia , Hedyeh Askarpour , Zohreh-Al-Sadat Ghoreshi , Habibeh Mashayekhi-Sardoo , Mohammad Ali-Hassanzadeh

Sjögren syndrome (SS) is one of the lesser-known autoimmune diseases, with its mechanisms and pathogenesis not yet fully understood. However, recent studies indicate that infectious diseases, such as Hepatitis C virus (HCV) infection, may serve as risk factors for the development of SS. Accordingly, this study aimed to estimate the global co-occurrence rate of chronic HCV infection and SS. In this systematic review and meta-analysis, a comprehensive search for relevant studies was conducted in PubMed, Scopus, ISI Web of Science, and Google Scholar databases up to June 2024. Data from eligible studies were meticulously extracted and statistically analyzed using Comprehensive Meta-Analysis Software. The pooled prevalence of co-occurrence of HCV and SS was calculated using incidence rates with 95 % confidence intervals (CIs), and the association of chronic HCV infection with the development of SS was assessed via odds ratios (ORs) with 95 % CIs. Analysis of the articles retrieved from the databases showed 24 studies were considered eligible. The pooled estimate for the co-occurrence of HCV and SS was approximately 16.6 % (95 % CI: 8.8–28.9). Moreover, the results indicated that chronic HCV infection significantly increased the risk of developing SS (OR: 2.76; 95 % CI: 1.35–5.63). This study's findings revealed that HCV infection may play a role in the pathogenesis of and susceptibility to SS. Therefore, chronic HCV infection may trigger the onset of SS. However, further studies are required to confirm these results.

Sjögren综合征（SS）是一种鲜为人知的自身免疫性疾病，其机制和发病机制尚不完全清楚。然而，最近的研究表明，感染性疾病，如丙型肝炎病毒（HCV）感染可能是SS发生的危险因素。因此，本研究旨在估计慢性HCV感染和SS的全球共发病率。在本系统综述和荟萃分析中，我们在PubMed、Scopus、ISI Web of Science和谷歌Scholar数据库中全面检索了截至2024年6月的相关研究。从符合条件的研究中提取数据，并使用综合meta分析软件进行统计分析。使用95%可信区间（ci）的发生率计算HCV和SS共发生的总患病率，并通过95% ci的优势比（ORs）评估慢性HCV感染与SS发生的相关性。从数据库中检索到的文章分析显示，24项研究被认为是合格的。HCV和SS共发生的合并估计约为16.6% （95% CI: 8.8-28.9）。此外，结果显示慢性HCV感染显著增加SS发生的风险(OR: 2.76；95% ci: 1.35-5.63)。本研究结果提示，HCV感染可能参与了SS的发病机制和易感性，因此慢性HCV感染可能触发SS的发病，但这些结果还需要进一步的研究来证实。

{"title":"The global prevalence of co-occurrence of Sjögren syndrome and Hepatitis C virus infection: A systematic review and meta-analysis","authors":"Nasir Arefinia , Hedyeh Askarpour , Zohreh-Al-Sadat Ghoreshi , Habibeh Mashayekhi-Sardoo , Mohammad Ali-Hassanzadeh","doi":"10.1016/j.virusres.2025.199585","DOIUrl":"10.1016/j.virusres.2025.199585","url":null,"abstract":"<div><div>Sjögren syndrome (SS) is one of the lesser-known autoimmune diseases, with its mechanisms and pathogenesis not yet fully understood. However, recent studies indicate that infectious diseases, such as Hepatitis C virus (HCV) infection, may serve as risk factors for the development of SS. Accordingly, this study aimed to estimate the global co-occurrence rate of chronic HCV infection and SS. In this systematic review and meta-analysis, a comprehensive search for relevant studies was conducted in PubMed, Scopus, ISI Web of Science, and Google Scholar databases up to June 2024. Data from eligible studies were meticulously extracted and statistically analyzed using Comprehensive Meta-Analysis Software. The pooled prevalence of co-occurrence of HCV and SS was calculated using incidence rates with 95 % confidence intervals (CIs), and the association of chronic HCV infection with the development of SS was assessed via odds ratios (ORs) with 95 % <em>CIs</em>. Analysis of the articles retrieved from the databases showed 24 studies were considered eligible. The pooled estimate for the co-occurrence of HCV and SS was approximately 16.6 % (95 % CI: 8.8–28.9). Moreover, the results indicated that chronic HCV infection significantly increased the risk of developing SS (OR: 2.76; 95 % CI: 1.35–5.63). This study's findings revealed that HCV infection may play a role in the pathogenesis of and susceptibility to SS. Therefore, chronic HCV infection may trigger the onset of SS. However, further studies are required to confirm these results.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199585"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080656","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

Recombinant adeno-associated virus 2-mediated miRNA-199 suppression vector alleviates dextran sulfate sodium-induced ulcerative colitis in mice 重组腺相关病毒2介导的miRNA-199抑制载体缓解硫酸葡聚糖钠诱导的小鼠溃疡性结肠炎。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2025-07-01 Epub Date: 2025-05-23 DOI: 10.1016/j.virusres.2025.199588

Wang Shanshan , Zhao Yu

Aim

Mouse colonic tissue was transfected with a recombinant adeno-associated virus (rAAV) 2 vector. We aimed to determine whether the rAAV vector could mediate gene expression in the colonic tissue and the role of microRNA (miRNA)-199a-5p in regulating the colonic inflammatory response in dextran sulfate sodium (DSS)-treated mice.

Methods

Different transfection methods and transfection times were found to be the most effective for mouse colonic tissue. The rAAV-miRNA-199a-5p vector (and control) was transfected into the colonic tissue of a mouse model of DSS-induced colitis. PCR was used to quantify miRNA and mRNA expression levels, and the TUNNEL assay was used to identify cellular regulation and histological alterations in colonic tissues.

Results

At three weeks following transfection, rAAV produced a higher transfection efficiency in colonic tissues via enucleation than via caudal vein injection and intraperitoneal injection. The colonic inflammatory response and apoptosis in mouse colonic tissues were reduced by miRNA-199a-5p inhibition.

Conclusion

rAAV can be used as a vector to inhibit gene expression in mouse colonic tissues. In mice with colitis, the rAAV-mediated suppression of miRNA-199a-5p reduces the inflammatory response.

目的：用重组腺相关病毒（rAAV） 2载体转染小鼠结肠组织。我们的目的是确定rAAV载体是否可以介导结肠组织中的基因表达，以及microRNA (miRNA)-199a-5p在调节葡聚糖硫酸钠（DSS）处理小鼠结肠炎症反应中的作用。方法：观察不同转染方法和转染次数对小鼠结肠组织的影响。将rAAV-miRNA-199a-5p载体（和对照）转染到dss诱导结肠炎小鼠模型的结肠组织中。采用PCR定量检测miRNA和mRNA的表达水平，采用TUNNEL法检测结肠组织的细胞调控和组织学改变。结果：转染后3周，rAAV通过去核在结肠组织中的转染效率高于尾静脉注射和腹腔注射。抑制miRNA-199a-5p可降低小鼠结肠组织的炎症反应和凋亡。结论：rAAV可作为抑制小鼠结肠组织基因表达的载体。在结肠炎小鼠中，raav介导的miRNA-199a-5p抑制可降低炎症反应。

{"title":"Recombinant adeno-associated virus 2-mediated miRNA-199 suppression vector alleviates dextran sulfate sodium-induced ulcerative colitis in mice","authors":"Wang Shanshan , Zhao Yu","doi":"10.1016/j.virusres.2025.199588","DOIUrl":"10.1016/j.virusres.2025.199588","url":null,"abstract":"<div><h3>Aim</h3><div>Mouse colonic tissue was transfected with a recombinant adeno-associated virus (rAAV) 2 vector. We aimed to determine whether the rAAV vector could mediate gene expression in the colonic tissue and the role of microRNA (miRNA)-199a-5p in regulating the colonic inflammatory response in dextran sulfate sodium (DSS)-treated mice.</div></div><div><h3>Methods</h3><div>Different transfection methods and transfection times were found to be the most effective for mouse colonic tissue. The rAAV-miRNA-199a-5p vector (and control) was transfected into the colonic tissue of a mouse model of DSS-induced colitis. PCR was used to quantify miRNA and mRNA expression levels, and the TUNNEL assay was used to identify cellular regulation and histological alterations in colonic tissues.</div></div><div><h3>Results</h3><div>At three weeks following transfection, rAAV produced a higher transfection efficiency in colonic tissues via enucleation than via caudal vein injection and intraperitoneal injection. The colonic inflammatory response and apoptosis in mouse colonic tissues were reduced by miRNA-199a-5p inhibition.</div></div><div><h3>Conclusion</h3><div>rAAV can be used as a vector to inhibit gene expression in mouse colonic tissues. In mice with colitis, the rAAV-mediated suppression of miRNA-199a-5p reduces the inflammatory response.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199588"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143626","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

Large-scale prediction shows that the dominant structure of the HIV-1 domain closed by the U5-AUG duplex contains the alternative SDa hairpin, and the domain variant without SD is rare 大规模预测表明，由U5-AUG双链关闭的HIV-1结构域的优势结构包含替代的SDa发夹，不含SD的结构域变体是罕见的。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2025-07-01 Epub Date: 2025-05-15 DOI: 10.1016/j.virusres.2025.199581

M.I. Zarudnaya, A.L. Potyahaylo, L.G. Gorb

Using several models of the HIV-1 5′ leader, it was shown that the domain containing the structural elements that regulate the processes of dimerization and genome packaging, as well as the initiation of reverse transcription, is closed by the U5-AUG duplex. However, there is no consensus in the literature on the structure of the upper part of this domain. Currently, the model proposed by Keane et al. in 2015 is dominant, although the question of whether it is general structure or specific to the experimental HIV-1 genome NL4–3 of subtype B remains open. To clarify this issue, we conducted large-scale in silico studies on the secondary structure of the domain closed by the U5-AUG duplex in 2754 HIV-1 genomes of different subtypes. Our investigation showed that the proportion of HIV-1 genomes in which the structure of the domain under study is similar to that in Keane et al. model is low. It forms mainly in HIV-1 genomes of subtype B with the frequency of 3.8 % in the optimal foldings or foldings with the energy increment of the lowest change in free energy (ΔΔG)<1.0 kcal/mol. In particular, certain base changes in common SD hairpin or base changes stabilizing Psi hairpin contribute to the formation of this domain variant. The dominant structure of the domain closed by the U5-AUG duplex is similar to that in Wilkinson et al. model (2008) but with the alternative SD hairpin. We found also new variants of this domain, which occur in foldings with ΔΔG<1.0 kcal/mol and may co-exist with dominant structure. However, it is possible that the variants of the domain closed by the U5-AUG duplex similar to Wilkinson et al. or Keane et al. models are formed only in the early stages of HIV-1 replication, while in the late stage (in the presence of nucleocapsid protein) the domain adopts structure similar to that in Sakuragi et al. (2012) model and the initiation of the reverse transcription occurs just in this structure. Extreme conservation of GACGC-GCGUC duplex, proposed in Sakuragi et al. model, supports this assumption.

利用几种hiv - 15 '先导体模型，研究人员发现，包含调控二聚化和基因组包装过程以及反转录起始的结构元件的结构域被U5-AUG双链关闭。然而，在文献中对该区域上部的结构没有共识。目前，Keane等人在2015年提出的模型占主导地位，尽管它是一般结构还是B亚型实验HIV-1基因组NL4-3特异性的问题仍然没有定论。为了澄清这一问题，我们对不同亚型的2754个HIV-1基因组中U5-AUG双链封闭结构域的二级结构进行了大规模的计算机研究。我们的研究表明，HIV-1基因组中所研究的结构域结构与Keane等人的模型相似的比例很低。它主要形成于HIV-1 B亚型基因组中，在最佳折叠或自由能变化最小的能量增量折叠中频率为3.8% （ΔΔG）。

{"title":"Large-scale prediction shows that the dominant structure of the HIV-1 domain closed by the U5-AUG duplex contains the alternative SDa hairpin, and the domain variant without SD is rare","authors":"M.I. Zarudnaya, A.L. Potyahaylo, L.G. Gorb","doi":"10.1016/j.virusres.2025.199581","DOIUrl":"10.1016/j.virusres.2025.199581","url":null,"abstract":"<div><div>Using several models of the HIV-1 5′ leader, it was shown that the domain containing the structural elements that regulate the processes of dimerization and genome packaging, as well as the initiation of reverse transcription, is closed by the U5-AUG duplex. However, there is no consensus in the literature on the structure of the upper part of this domain. Currently, the model proposed by Keane et al. in 2015 is dominant, although the question of whether it is general structure or specific to the experimental HIV-1 genome NL4–3 of subtype B remains open. To clarify this issue, we conducted large-scale <em>in silico</em> studies on the secondary structure of the domain closed by the U5-AUG duplex in 2754 HIV-1 genomes of different subtypes. Our investigation showed that the proportion of HIV-1 genomes in which the structure of the domain under study is similar to that in Keane et al. model is low. It forms mainly in HIV-1 genomes of subtype B with the frequency of 3.8 % in the optimal foldings or foldings with the energy increment of the lowest change in free energy (ΔΔG)<1.0 kcal/mol. In particular, certain base changes in common SD hairpin or base changes stabilizing Psi hairpin contribute to the formation of this domain variant. The dominant structure of the domain closed by the U5-AUG duplex is similar to that in Wilkinson et al. model (2008) but with the alternative SD hairpin. We found also new variants of this domain, which occur in foldings with ΔΔG<1.0 kcal/mol and may co-exist with dominant structure. However, it is possible that the variants of the domain closed by the U5-AUG duplex similar to Wilkinson et al. or Keane et al. models are formed only in the early stages of HIV-1 replication, while in the late stage (in the presence of nucleocapsid protein) the domain adopts structure similar to that in Sakuragi et al. (2012) model and the initiation of the reverse transcription occurs just in this structure. Extreme conservation of GACGC-GCGUC duplex, proposed in Sakuragi et al. model, supports this assumption.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199581"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095156","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

Validation of signature molecular profiles of advanced HCV liver disease in hepatocellular carcinoma patients 肝细胞癌患者晚期HCV肝病特征分子谱的验证

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2025-07-01 Epub Date: 2025-06-07 DOI: 10.1016/j.virusres.2025.199593

In-Woo Park, Hope K. Fiadjoe, Tamara Hoteit, Pankaj Chaudhary

Our previous transcriptome analysis revealed that hepatitis C virus (HCV) infection in hepatocytes regulates the expression of numerous hepatocellular genes in a liver disease stage-specific manner. Based on the fold changes at different stages and the known relevant function of the cellular genes with respect to hepatocellular carcinoma (HCC) and through comprehensive examination with various in silico assays, such as heatmap and volcano analysis for the differential expression, the Cancer Genome Atlas - Hepatocellular Carcinoma (TCGA-HCC) analysis, and molecular approaches, such as qRT-PCR, immunoblot analyses, we have chosen the two up-regulated genes - aldo-keto reductase family 1 member B10 (AKR1B10) and hexokinase domain containing 1 (HKDC1), and two down-regulated genes - glycine N-methyltransferase (GNMT) and C-type lectin domain family 4, member M (CLEC4M), and validated their differential expressions of the genes at disparate stages of liver disease with respect to the development of potential therapeutic targets against HCV-mediated hepatocellular carcinoma (HCC). These data suggested that the differentially expressed genes at various stages could serve as prognostic and diagnostic markers for liver disease progression and may also be utilized in developing therapeutic drugs.

我们之前的转录组分析显示，肝细胞中的丙型肝炎病毒（HCV）感染以肝脏疾病阶段特异性的方式调节许多肝细胞基因的表达。基于肝细胞癌（HCC）在不同阶段的fold变化和已知的细胞基因的相关功能，通过各种计算机分析，如热图和火山分析的差异表达，癌症基因组图谱-肝细胞癌（TCGA-HCC）分析，以及分子方法，如qRT-PCR，免疫印迹分析，我们选择了两个上调基因——醛酮还原酶家族1成员B10 （AKR1B10）和己糖激酶结构域1 (HKDC1)，以及两个下调基因——甘氨酸n-甲基转移酶（GNMT）和c型凝集素结构域家族4成员M (CLEC4M)，并验证了它们在肝脏疾病不同阶段的差异表达，以开发针对hcv介导的肝细胞癌（HCC）的潜在治疗靶点。这些数据表明，不同阶段的差异表达基因可以作为肝脏疾病进展的预后和诊断标记，也可以用于开发治疗药物。

{"title":"Validation of signature molecular profiles of advanced HCV liver disease in hepatocellular carcinoma patients","authors":"In-Woo Park, Hope K. Fiadjoe, Tamara Hoteit, Pankaj Chaudhary","doi":"10.1016/j.virusres.2025.199593","DOIUrl":"10.1016/j.virusres.2025.199593","url":null,"abstract":"<div><div>Our previous transcriptome analysis revealed that hepatitis C virus (HCV) infection in hepatocytes regulates the expression of numerous hepatocellular genes in a liver disease stage-specific manner. Based on the fold changes at different stages and the known relevant function of the cellular genes with respect to hepatocellular carcinoma (HCC) and through comprehensive examination with various in silico assays, such as heatmap and volcano analysis for the differential expression, the Cancer Genome Atlas - Hepatocellular Carcinoma (TCGA-HCC) analysis, and molecular approaches, such as qRT-PCR, immunoblot analyses, we have chosen the two up-regulated genes - aldo-keto reductase family 1 member B10 (AKR1B10) and hexokinase domain containing 1 (HKDC1), and two down-regulated genes - glycine N-methyltransferase (GNMT) and C-type lectin domain family 4, member M (CLEC4M), and validated their differential expressions of the genes at disparate stages of liver disease with respect to the development of potential therapeutic targets against HCV-mediated hepatocellular carcinoma (HCC). These data suggested that the differentially expressed genes at various stages could serve as prognostic and diagnostic markers for liver disease progression and may also be utilized in developing therapeutic drugs.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"357 ","pages":"Article 199593"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258958","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