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New lytic and new temperate Staphylococcus hyicus phages. 新型裂解性和温带葡萄球菌噬菌体。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2025-06-01 Epub Date: 2025-03-14 DOI: 10.1007/s11262-025-02151-5
Karel Petrzik, Lucie Sovová

A novel lytic phage with a broad host range was isolated from pig faeces and the complete genome was subsequently sequenced. The phage was found to lyse Staphylococcus hyicus, S. pseudintermedius, S. schleiferi and S. warneri, generating approximately 27 PFU per infected S. hyicus cell. The phage has an isometric head of 42 ± 2 nm in diameter and a noncontractile tail of 114 ± 9 nm long. The genome is 53,660 bp in size and consists of 79 predicted ORFs and one tRNAArg gene. The phage has been classified within the Caudoviricetes, specifically the Chaseviridae family. Its broad host range and absence of harmful genes make it suitable for use in phage therapy. In addition, a novel temperate phage was discovered that was spontaneously released from a S. hyicus isolate Pel11 from a pig with exudative epidermitis. This novel temperate phage differs from the known temperate phages in S. hyicus strains NCTC10350, MM2101 or 83/7-1B, representing a novel pathogenicity element in the S. hyicus genome.

从猪粪便中分离出一种具有广泛宿主范围的新型裂解噬菌体,并随后对其全基因组进行了测序。该噬菌体可裂解葡萄球菌、假中间葡萄球菌、施莱费氏葡萄球菌和沃纳氏葡萄球菌,每个感染的葡萄球菌细胞产生约27个PFU。该噬菌体有直径42±2 nm的等距头部和114±9 nm长的不可收缩尾部。基因组大小为53,660 bp,由79个预测orf和1个tRNAArg基因组成。噬菌体被归类为尾状病毒科,特别是追逐病毒科。其广泛的宿主范围和不含有害基因使其适合用于噬菌体治疗。此外,还发现了一种新的温带噬菌体,该噬菌体从猪的渗出性表皮炎中自然释放出来。这种新的温带噬菌体不同于已知的hyicus菌株NCTC10350、MM2101或83/7-1B的温带噬菌体,代表了hyicus基因组中一个新的致病性元件。
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引用次数: 0
Norovirus GI.5 [P4]: first report of the rare norovirus recombinant variant in Northeastern Mexico and its global epidemiological context. 诺如病毒GI.5 [P4]:首次报道墨西哥东北部罕见的诺如病毒重组变体及其全球流行病学背景。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2025-06-01 Epub Date: 2025-02-22 DOI: 10.1007/s11262-025-02144-4
José Antonio Cortés-Trigueros, Axel Ossio, Norma Heredia, Néstor Casillas-Vega, Santos García, Jose Angel Merino-Mascorro

Norovirus is the primary cause of acute gastroenteritis outbreaks, considerably impacting children under 5 years, followed by older adults and immunocompromised individuals. As an RNA virus, norovirus exhibits high genetic variability, driven by recombination events at the ORF1-ORF2 junction. This study reports the first detection of the rare norovirus GI.5 [P4] variant in Northeastern Mexico, identified in a single positive isolate (MTY0115; GenBank: PQ369661) from a sample group of 386 individuals, with a prevalence of 0.25%. Notably, norovirus GII was not detected. Phylogenetic analysis of the partial RdRp/VP1 region revealed clustering with global GI.5 [P4] sequences, revealing evolutionary relationships with isolates from Asia, Europe, and America. A recombination event was identified at position 5307 (breakpoint based on reference sequences of GI.5 [P5] and GI.4 [P4]) within ORF1, with genetic inheritance from a GI.5 [P5] isolate from Moscow, Russia, and a GI.4 [P4] isolate from France. Typing classification through sequencing of overlapping ORF1 and ORF2 regions is valuable for understanding genomic variations and their epidemiological impact on at-risk and non-risk populations.

诺如病毒是急性肠胃炎暴发的主要原因,严重影响5岁以下儿童,其次是老年人和免疫功能低下的个体。作为一种RNA病毒,诺如病毒表现出高度的遗传变异性,这是由ORF1-ORF2连接处的重组事件驱动的。本研究报告了在墨西哥东北部首次检测到罕见的诺如病毒GI.5 [P4]变体,在单个阳性分离物(MTY0115;GenBank: PQ369661),来自386个个体的样本组,患病率为0.25%。值得注意的是,没有检测到诺如病毒GII。部分RdRp/VP1区域的系统发育分析显示与全球GI.5 [P4]序列聚类,揭示了与亚洲、欧洲和美洲分离株的进化关系。在ORF1基因的5307位点(基于GI.5 [P5]和GI.4 [P4]参考序列的断点)发现重组事件,遗传自俄罗斯莫斯科的GI.5 [P5]和法国的GI.4 [P4]分离株。通过重叠ORF1和ORF2区域的测序进行分型分类对于了解基因组变异及其对高危人群和非高危人群的流行病学影响具有重要意义。
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引用次数: 0
Plasma proteins and herpes simplex virus infection: a proteome-wide Mendelian randomization study. 血浆蛋白与单纯疱疹病毒感染:一项蛋白质组范围的孟德尔随机研究。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2025-06-01 Epub Date: 2025-02-24 DOI: 10.1007/s11262-025-02145-3
Canya Fu, Wenjie Xu, Xia Xu, Fei Zhao, Canjie Zheng, Zhiying Yin

Proteomics plays a pivotal role in clinical diagnostics and monitoring. We conducted proteome-wide Mendelian randomization (MR) study to estimate the causal association between plasma proteins and Herpes simplex virus (HSV) infection. Data for 2,923 plasma protein levels were obtained from a large-scale protein quantitative trait loci study involving 54,219 individuals, conducted by the UK Biobank Pharma Proteomics Project. HSV-associated SNPs were derived from the FinnGen study, which included a total of 400,098 subjects infected with HSV. MR analysis was performed to assess the links between protein levels and the risk of HSV infection. Furthermore, a Phenome-wide MR analysis was utilized to explore potential alternative indications or predict adverse drug events. Finally, we evaluated the impact of 1,949 plasma proteins on HSV infection, identifying 48 proteins that were negatively associated with HSV infection and 54 proteins that were positively associated. Genetically higher HLA-E levels were significantly associated with increased HSV infection risk (OR = 1.39, 95% CI: 1.17-1.65, P = 2.13 × 10-4, while ULBP2 showed a significant negative association with HSV infection risk (OR = 0.81, 95% CI: 0.73-0.90, P = 6.25 × 10-5) in the primary analysis. No significant heterogeneity or pleiotropy was observed in any of the results. Additionally, we found a suggestive association of Lymphotoxin-beta, SMOC1, MICB_MICA, ASGR1, and ANXA10 with HSV infection risk (P < 0.003). In Phenome-wide MR analysis, HLA-E was associated with 214 phenotypes (PFDR < 0.10) while ULBP2 did not show significant associations with any diseases after FDR adjustment. The comprehensive MR analysis established a causal link between multiple plasma proteins and HSV infection, emphasizing the roles of HLA-E and ULBP2. These results provide new insights into the biological mechanisms of HSV and support the potential for early intervention and treatment strategies, although further research is needed to validate these plasma protein biomarkers.

蛋白质组学在临床诊断和监测中起着关键作用。我们进行了蛋白组范围内孟德尔随机化(MR)研究,以估计血浆蛋白与单纯疱疹病毒(HSV)感染之间的因果关系。2923个血浆蛋白水平的数据来自一项大规模蛋白质定量性状位点研究,该研究由英国生物银行制药蛋白质组学项目进行,涉及54,219个个体。单纯疱疹病毒相关snp来自FinnGen研究,该研究共包括400,098名感染单纯疱疹病毒的受试者。进行MR分析以评估蛋白水平与HSV感染风险之间的联系。此外,全现象级磁共振分析被用于探索潜在的替代适应症或预测药物不良事件。最后,我们评估了1949种血浆蛋白对HSV感染的影响,发现48种蛋白与HSV感染呈负相关,54种蛋白与HSV感染呈正相关。遗传上较高的HLA-E水平与HSV感染风险增加显著相关(OR = 1.39, 95% CI: 1.17-1.65, P = 2.13 × 10-4),而ULBP2与HSV感染风险呈显著负相关(OR = 0.81, 95% CI: 0.73-0.90, P = 6.25 × 10-5)。在任何结果中均未观察到显著的异质性或多效性。此外,我们还发现lyphotoxin - β、SMOC1、MICB_MICA、ASGR1和ANXA10与HSV感染风险存在相关性
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引用次数: 0
Decoding codon usage in human papillomavirus type 59. 人乳头瘤病毒59型解码密码子的使用。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2025-06-01 Epub Date: 2025-03-04 DOI: 10.1007/s11262-025-02148-0
Xiaochun Tan, Wenyi Zhou, Shunyou Jing, Weifeng Shen, Binbin Lu

Human Papillomavirus Type 59 (HPV-59) is a high-risk subtype linked to cervical and other cancers. However, its codon usage patterns remain underexplored despite their importance in understanding viral behavior and vaccine optimization. This study reveals a mild codon usage bias in HPV-59, with a notable preference for A/T-ending codons and 29 favored codons, primarily ending in A or T. Additionally, CpG dinucleotides were significantly underrepresented, potentially aiding immune evasion. Analyses using the Parity Rule 2, Effective Number of Codons plot, and neutrality plot indicate that both mutational pressure and natural selection shape codon usage, with natural selection playing a dominant role. The virus's codon usage moderately aligns with human translational machinery, as shown by the Isoacceptor tRNA pool, Codon Adaptation Index, and Relative Codon Deoptimization Index, reflecting an evolutionary balance between protein synthesis efficiency and host compatibility. These findings provide valuable insights into HPV-59 biology, offering guidance for developing optimized vaccines.

人类乳头瘤病毒59型(HPV-59)是一种与宫颈癌和其他癌症有关的高风险亚型。然而,它的密码子使用模式仍未被充分探索,尽管它们在理解病毒行为和疫苗优化方面很重要。该研究揭示了HPV-59中轻微的密码子使用偏好,对a / t结尾的密码子和29个主要以a或t结尾的密码子有明显的偏好。此外,CpG二核苷酸的代表性明显不足,可能有助于免疫逃避。利用奇偶规则2、有效密码子数图和中性图分析表明,突变压力和自然选择共同决定了密码子的使用,其中自然选择起主导作用。病毒的密码子使用与人类的翻译机制大致一致,如异受体tRNA库、密码子适应指数和相对密码子去优化指数所示,反映了蛋白质合成效率和宿主兼容性之间的进化平衡。这些发现为HPV-59生物学提供了有价值的见解,为开发优化疫苗提供了指导。
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引用次数: 0
Alphanudiviral segments found in transcriptomes of the two-spotted spider mite, Tetranychus urticae (Acari: Tetranychidae). 在荨麻疹叶螨(螨亚纲:叶螨科)双斑蜘蛛螨转录组中发现的甲病毒片段。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2025-06-01 Epub Date: 2025-03-21 DOI: 10.1007/s11262-025-02150-6
Ethiane Rozo Santos, Jirka Manuel Petersen, Thaís Danielle Duarte Santana, Robert L Harrison, Daniel M P Ardisson-Araújo

Nudiviruses (family Nudiviridae) are a diverse group of enveloped, rod-shaped viruses with double-stranded DNA genomes that infect a wide range of insects and crustaceans. These viruses are of significance both as biological control agents in agriculture and as agents of disease in aquaculture and insect rearing. In this work, we found four segments of a novel and divergent nudivirus identified through RNA-seq data from the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae). The sequences of this virus were detected only in a subset of mite transcriptomes. The assembled segments covered a total of 100,780 bp, with 122 annotated ORFs, including all the 28 conserved nudiviral core genes. Phylogenetic analysis based on the predicted amino acid sequences of 17 selected nudiviral core genes placed the virus within the Alphanudivirus genus, in a clade containing nudiviruses identified from flea transcriptomes. This placement was confirmed by phylogenies of segment-specific concatenated core gene alignments. Indeed, the virus was designated as Tetranychus urticae alphanudivirus (TuNV). Transcriptional profiling revealed variable levels of transcriptional activity among genomic segments and viral genes. Arthropod gene homologs were found interspersed among nudiviral genes across all segments along with several unique genes. This genomic and phylogenetic characterization enhances our understanding of nudivirus diversity and evolution within arthropod hosts.

裸病毒(裸病毒科)是一种包膜的杆状病毒,具有双链DNA基因组,可感染多种昆虫和甲壳类动物。这些病毒在农业中作为生物防治剂,在水产养殖和昆虫饲养中作为致病剂具有重要意义。在这项工作中,我们发现了一种新的和不同的裸病毒的四个片段,通过RNA-seq数据从双斑蜘蛛螨中鉴定,荨麻疹叶螨(螨目:叶螨科)。该病毒序列仅在螨转录组的一个子集中检测到。组装的片段总长度为100,780 bp,有122个带注释的orf,包括所有28个保守的裸病毒核心基因。根据17个选定的裸病毒核心基因的预测氨基酸序列进行系统发育分析,将该病毒置于从跳蚤转录组中鉴定出的含有裸病毒的甲病毒属分支中。这种定位被片段特异性串联核心基因序列的系统发育所证实。事实上,这种病毒被命名为荨麻疹叶螨甲病毒(TuNV)。转录谱分析揭示了基因组片段和病毒基因之间不同水平的转录活性。节肢动物基因的同源性分布在裸病毒基因的各个片段中,并有几个独特的基因。这种基因组和系统发育特征增强了我们对节肢动物宿主内裸病毒多样性和进化的理解。
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引用次数: 0
Phylogenetic analyses of the spread of Clade I MPOX in African and non-African nations. 进化支I型MPOX在非洲和非非洲国家传播的系统发育分析。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2025-06-01 Epub Date: 2025-02-12 DOI: 10.1007/s11262-025-02138-2
Chiranjib Chakraborty, Manojit Bhattacharya, Arpita Das, Ali S Abdelhameed

Recently, mpox has spread in some parts of Africa, such as Congo (DRC), Burundi, Rwanda, Uganda, and Kenya, worsening the situation in DRC and Burundi compared to the other parts of Africa due to the spread of the Clade Ib, with several confirmed and lethal cases. The study aims to analyze the broader molecular phylogenetics using greater complete genome sequences and molecular phylogenetics of Clade I (Clade Ia and Clade Ib), nucleotide diversity of the genome of Clade I, NGA/TCN context of G- > A/C- > T mutations, and epidemiology of the recent spread of mpox in the African countries. Overall molecular phylogenetics of mpox inform the divergence was noted between 0.00220 and 0.00265 and found Clade IIb has further subdivided into 37 sublineages. From our phylogenetic analysis and the tracking of recent mpox variants, we report the spread of Clade I (Clade Ib) of mpox, a virulent mpox, in the African continent, Thailand, Sweden, and USA. Furthermore, two Clades, Clade Ia and Clade Ib, have originated from Clade I. Recently, Clade Ib has expanded its region within African continent. We reported the mutation pattern in the genome. Epidemiological analysis indicates the most affected country is the Democratic Republic of the Congo (DRC). This work shows that mpox is steadily adapting as geographic area increases and can help the health authorities develop policies such as vaccinations, and travel restrictions to contain the spread of mpox.

最近,麻疹已在非洲一些地区蔓延,如刚果(金)、布隆迪、卢旺达、乌干达和肯尼亚,与非洲其他地区相比,刚果(金)和布隆迪的情况因埃博拉病毒的传播而恶化,出现了几例确诊和致命病例。本研究旨在分析更广泛的分子系统发育,使用更完整的基因组序列和进化枝I(进化枝Ia和进化枝Ib)的分子系统发育,进化枝I基因组的核苷酸多样性,G- > A/C- > T突变的NGA/TCN背景,以及最近在非洲国家传播的麻疹流行病学。mpox的总体分子系统发育表明,分化在0.00220和0.00265之间,并发现分支IIb进一步细分为37个亚谱系。根据我们的系统发育分析和对近期m痘变异的追踪,我们报告了m痘I (Clade Ib)的传播,这是一种剧毒的m痘,在非洲大陆、泰国、瑞典和美国。此外,进化枝Ia和进化枝Ib起源于进化枝i。最近,进化枝Ib在非洲大陆扩展了其区域。我们报告了基因组中的突变模式。流行病学分析表明,受影响最严重的国家是刚果民主共和国。这项工作表明,随着地理区域的增加,mpox正在稳步适应,可以帮助卫生当局制定诸如疫苗接种和旅行限制等政策,以遏制mpox的传播。
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引用次数: 0
Complete genome and molecular characterization of spiranthes mosaic virus 3 from Phlox paniculata. 夹竹桃螺旋体花叶病毒3型全基因组及分子特征分析。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2025-06-01 Epub Date: 2025-02-27 DOI: 10.1007/s11262-025-02147-1
Elena Motsar, Fedor Sharko, Anna Sheveleva, Larisa Savostyanova, Irina Mitrofanova, Sergei Chirkov

The first complete genome of spiranthes mosaic virus 3 (SpiMV3, genus Potyvirus, Potyviridae) was determined using high-throughput sequencing (GenBank PQ374234). The virus was detected from a Phlox paniculata plant, displaying severe foliar mosaic, in the Botanical Garden of Lomonosov Moscow State University, Moscow, Russia. The complete SpiMV3 genome comprised 9544 nucleotides (nt), excluding the 3'-terminal poly(A) tail. The large open-reading frame 9258 nt long encoded a polyprotein of 3085 amino acid residues, in which nine putative cleavage sites were identified. BLASTn showed that the complete SpiMV3 genome had the highest identity (66.4%) to Colombian datura potyvirus. Eight more SpiMV3 isolates were found on different phlox cultivars in the Tsitsin Main Botanical Garden, Moscow, by RT-PCR using primers designed based on the complete genome of the Russian SpiMV3 isolate. The coat protein (CP) gene phylogeny showed that known SpiMV3 isolates formed two distinct clusters and were grouped irrespective of their host plant species or geographical origin. The Russian isolates were assigned to one of the clusters. The CP genes of the Russian SpiMV3 isolates shared 94.4-98.1% nucleotide identity to each other, 92.2-96.9% to the rest of the isolates from this group, and 72.7-75.6% to the isolates from another cluster. This is the first report of SpiMV3 from Russia expanding the information on the geographical distribution and genetic diversity of the virus. The complete genome of this virus was sequenced and characterized for the first time.

采用高通量测序技术(GenBank PQ374234)测定了螺旋体花叶病毒3 (SpiMV3, Potyvirus属,Potyvirus科)的首个全基因组。该病毒是从俄罗斯莫斯科罗蒙诺索夫莫斯科国立大学植物园的一株鳞片花叶严重的穿山甲植物中检测到的。完整的SpiMV3基因组包含9544个核苷酸(nt),不包括3'端多聚(A)尾。大的开放阅读框9258 nt长编码3085个氨基酸残基的多蛋白,其中鉴定出9个假定的裂解位点。BLASTn结果显示,SpiMV3全基因组与哥伦比亚曼陀罗痘病毒的同源性最高(66.4%)。利用俄罗斯SpiMV3分离株全基因组设计的引物进行RT-PCR,在莫斯科ttsisin Main Botanical Garden的不同夹竹桃品种中又发现了8株SpiMV3分离株。外壳蛋白(CP)基因的系统发育表明,已知的SpiMV3分离株形成两个不同的簇,并且与寄主植物种类或地理来源无关。俄罗斯分离株被分配到其中一个聚集群。俄罗斯SpiMV3分离株的CP基因同源性为94.4 ~ 98.1%,该群分离株的CP基因同源性为92.2 ~ 96.9%,另一群分离株的CP基因同源性为72.7 ~ 75.6%。这是俄罗斯SpiMV3的第一份报告,扩大了关于该病毒的地理分布和遗传多样性的信息。首次对该病毒的全基因组进行了测序和鉴定。
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引用次数: 0
Construction and efficacy of a recombinant QX-like infectious bronchitis virus vaccine strain. 重组qx样传染性支气管炎病毒疫苗株的构建及疗效观察。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2025-06-01 Epub Date: 2025-02-27 DOI: 10.1007/s11262-025-02140-8
Lin Lin, Keyu Feng, Guanming Shao, Shiying Gong, Tongfei Liu, Feng Chen, Xinheng Zhang, Qingmei Xie

Infectious bronchitis (IB) is a highly contagious disease caused by the avian infectious bronchitis virus (IBV). This disease mainly causes damage to the respiratory system and has brought serious harm to the poultry industry in China. At present, QX-like IBV is the most prevalent strain in China, which is highly pathogenic and causes severe nephritis. Based on the construction of the H120 infectious clone, this study successfully constructed and rescued the recombinant virus H120-S1/LMH by using RED/ET recombination engineering technology combined with ccdB reverse selection to replace the S1 gene of the H120 infectious clone with the S1 gene of the prevalent IBV LMH strain. The recombinant virus showed good genetic stability and propagation in 15 continuous generations on chick kidney cells (CK cells). To evaluate the protection of this candidate vaccine strain, we conducted a vaccination challenge test. The specific-pathogen-free (SPF) chicks were immunized at 3 days of age and challenged with the QX-like IBV virulent strain LMH after 14 days. The results showed that the recombinant virus could provide 90% protection against the virulent IBV LMH strain, and mortality was significantly reduced, indicating the potential of H120-S1/LMH as a candidate vaccine. This study provides a strategy for precisely and rapidly generating IBV vaccine candidates by reverse genetics and lays a foundation for the further development of a new IBV vaccine against prevalent strains.

传染性支气管炎(IB)是由禽传染性支气管炎病毒(IBV)引起的高度传染性疾病。该病主要对呼吸系统造成损害,对中国家禽业造成严重危害。目前,qx样IBV是中国最流行的菌株,具有高致病性,可引起严重的肾炎。本研究在构建H120感染性克隆的基础上,利用RED/ET重组工程技术结合ccdB逆选,成功构建并挽救了重组病毒H120-S1/LMH,将H120感染性克隆的S1基因替换为流行IBV LMH株的S1基因。重组病毒在鸡肾细胞(CK细胞)上具有良好的遗传稳定性和连续15代的繁殖能力。为了评估该候选疫苗株的保护作用,我们进行了疫苗激发试验。SPF雏鸡在3日龄免疫,14天后用qx样IBV毒力株LMH攻毒。结果表明,重组病毒对IBV LMH毒株的保护率为90%,死亡率显著降低,表明H120-S1/LMH有作为候选疫苗的潜力。本研究为通过反向遗传学精确、快速地产生IBV候选疫苗提供了一种策略,并为进一步开发针对流行菌株的新型IBV疫苗奠定了基础。
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引用次数: 0
Robust antiviral innate immune response and miRNA regulatory network were identified in ZIKV-infected cells: implications in the pathogenesis of ZIKV infection. 在寨卡病毒感染的细胞中发现了强大的抗病毒先天免疫反应和miRNA调节网络:在寨卡病毒感染的发病机制中的意义。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2025-06-01 Epub Date: 2025-02-16 DOI: 10.1007/s11262-025-02136-4
Mingshuang Lai, Rongji Lai, Baoren He, Xinwei Wang, Limin Chen, Qiuhong Mo

Zika virus (ZIKV) infection has emerged as a significant public health concern due to its association with fetal microcephaly and Guillain-Barre syndrome (GBS). Unfortunately, its detailed pathogenesis remains unclear. To better understand how ZIKV evades host antiviral immunity, we analyzed the microarray dataset (GSE98889) of ZIKV-infected primary human brain microvascular endothelial cells (hBMECs) retrieved from the gene expression omnibus (GEO). 160, 1423, 969, 829, and 600 differentially expressed genes (DEGs) were identified at 12, 24, 48, 72, and 216 hours post-ZIKV infection in hBMECs, respectively. Subsequently, 31 common DEGs across all time-points were selected for further analysis. Gene ontology (GO) functional analysis showed these 31 DEGs were mainly involved in the host antiviral innate immune responses. Protein-protein interaction (PPI) network analysis identified 10 hub genes (MX1, OAS1, OAS2, IFI44, IFI44L, IFIT1, IFIT2, IFIT3, IFIH1, and XAF1), which were all interferon-stimulated genes (ISGs) and upregulated. qRT-PCR was used to validate the expression patterns of these 10 hub genes in different ZIKV-infected cell lines. Finally, miRNA-mRNA regulatory network analysis revealed that hsa-miR-129-2-3p, hsa-miR-138-5p, hsa-miR-21-3p, hsa-miR-27a-5p, hsa-miR-449a, and hsa-miR449b-5p were key miRNAs regulating these hub genes. Our study showed that ZIKV infection activated the host innate immune response to restrict ZIKV infection. The common pathways, hub genes, and their regulatory miRNA network offer new insights into virus-host interactions, enhancing our understanding of ZIKV pathogenesis.

由于寨卡病毒(ZIKV)感染与胎儿小头畸形和格林-巴利综合征(GBS)有关,它已成为一个重大的公共卫生问题。遗憾的是,其详细的发病机制仍不清楚。为了更好地了解 ZIKV 如何逃避宿主的抗病毒免疫,我们分析了从基因表达总库(GEO)中检索到的 ZIKV 感染的原代人脑微血管内皮细胞(hBMECs)的微阵列数据集(GSE98889)。在 hBMECs 感染 ZIKV 后 12、24、48、72 和 216 小时,分别鉴定出 160、1423、969、829 和 600 个差异表达基因(DEGs)。随后,选择了所有时间点的 31 个常见 DEGs 进行进一步分析。基因本体(GO)功能分析显示,这31个DEGs主要参与宿主抗病毒先天免疫反应。蛋白-蛋白相互作用(PPI)网络分析确定了10个枢纽基因(MX1、OAS1、OAS2、IFI44、IFI44L、IFIT1、IFIT2、IFIT3、IFIH1和XAF1),它们都是干扰素刺激基因(ISGs),并且上调。最后,miRNA-mRNA调控网络分析显示,hsa-miR-129-2-3p、hsa-miR-138-5p、hsa-miR-21-3p、hsa-miR-27a-5p、hsa-miR-449a和hsa-miR449b-5p是调控这些枢纽基因的关键miRNA。我们的研究表明,ZIKV感染激活了宿主的先天免疫反应,从而限制了ZIKV感染。共同途径、枢纽基因及其调控miRNA网络为病毒与宿主的相互作用提供了新的见解,加深了我们对ZIKV发病机制的理解。
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引用次数: 0
Molecular characterization and drug resistance pattern in pol gene of HIV-1 sub-subtypes circulating in Lahore, Pakistan. 巴基斯坦拉合尔流行HIV-1亚型pol基因的分子特征和耐药模式
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2025-06-01 Epub Date: 2025-03-27 DOI: 10.1007/s11262-025-02149-z
Akmal Zubair, Adnan Zeb, Syed Ahsan Shahid, Hasnain Javed, Muhammad Ali

This study aimed to determine sub-subtypes and circulating recombinant forms (CRFs) in Pakistan using the pol gene, identification of amino acid substitutions, structural changes, and drug resistance evaluation in the p66 region of reverse transcriptase. A total of 50 HIV-positive blood samples were collected from Lahore Pakistan, confirmed by Real Time-Polymerase Chain Reaction. The samples were further processed for pol gene amplification followed by nucleotide sequencing through the Sanger method. Out of 50 samples, 26 samples were amplified, and 14 sequences were obtained. The sequences were aligned with reference sequences to determine subtyping and phylogenetic analysis. Moreover, amino acid substitutions and drug resistance patterns were also determined in the RTp66 region. Phylogenetic analysis showed that 8 sequences of our isolates were closely related to circulating recombinant form (CRF43_02 G), and 3 sequences were of CRF30_026 (CRF02_AG) subtypes while the remaining 3 sequences were related to CRF35_A1D, CRF95_02B (CRF02_AG) and Subtype G of HIV-1. Several amino acid substitutions were identified in our isolates which show no impact on the structure of protein. Furthermore, the isolate QAU-AZ2 (OR086936) proposes variable degree of resistance to nevirapine (NVP), etravirine (ETR), rilpivirine (RPV), efavirenz (EFV), Doravirine (DOR); while no resistance against NNTRI and NTRI was observed in the remaining isolates. Further studies are required to (i) examine the function of identified amino acid substitutions through molecular docking, and (ii) sequence the complete pol gene of the viral isolates from Pakistani patients to determine possible drug resistance associated with amino acid substitutions.

本研究旨在利用pol基因,鉴定逆转录酶p66区域的氨基酸取代,结构变化和耐药性评估,确定巴基斯坦的亚亚型和循环重组形式(CRFs)。在巴基斯坦拉合尔共收集了50份艾滋病毒阳性血液样本,经实时聚合酶链反应证实。进一步对样品进行pol基因扩增和Sanger法核苷酸测序。在50个样本中,扩增了26个样本,获得了14个序列。将这些序列与参考序列比对以确定亚型和系统发育分析。此外,还测定了RTp66区域的氨基酸取代和耐药模式。系统发育分析表明,8个序列与循环重组形式(CRF43_02 G)密切相关,3个序列为CRF30_026 (CRF02_AG)亚型,其余3个序列与HIV-1的CRF35_A1D、CRF95_02B (CRF02_AG)和G亚型相关。在我们的分离株中发现了几个氨基酸取代,但对蛋白质结构没有影响。此外,分离物QAU-AZ2 (OR086936)对奈韦拉平(NVP)、依曲维林(ETR)、利匹韦林(RPV)、依非韦伦(EFV)、多拉韦林(DOR)具有不同程度的耐药;其余分离株对NNTRI和NTRI均无抗性。需要进一步的研究:(i)通过分子对接检查已鉴定的氨基酸取代的功能,以及(ii)对来自巴基斯坦患者的病毒分离株的完整pol基因进行测序,以确定与氨基酸取代相关的可能的耐药性。
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