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STAT5-c-Myc-axis regulates B cell metabolism in vaccinated individuals and COVID-19 recovered patients stat5 -c- myc轴调节接种疫苗个体和COVID-19康复患者的B细胞代谢。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.003
Lu Yang , Linhua Wang , Qian Liu , Xu Zhang , Yuexin Luo , Junbiao Xue , Xinpu Yang , Maria G. Byazrova , Alexander V. Filatov , Sheng-Ce Tao , Wei Xiao , Chaohong Liu
SARS-CoV-2 infection and vaccination both trigger immune responses. The former leads to naturally acquired immunity, while the latter induces active immunity through artificial means. However, the distinct immune effects of vaccination and infection, as well as their underlying mechanisms, require further clarification. In this study, we compared the peripheral B cell differentiation, serological differences and the expression level of BCR signaling molecules between the vaccinated and recovered group. The vaccinated group exhibited reduced RBD-specific B cell differentiation and lower CD86 signal intensity on memory B cells, but enhanced BCR signaling in B cells. Regarding metabolic signaling, the vaccinated group had elevated expression levels of pS6, c-Myc, pmTOR, and pSTAT5, suggesting that the STAT5-c-Myc axis plays a role in regulating B cell metabolism. Additionally, proteome microarray analysis revealed that the serum of the vaccinated group contained higher levels of IgG antibodies against the SARS-CoV-2 N-Nter protein and IgA antibodies specific to the SARS-CoV-2 S1 protein. In summary, these findings indicate that the vaccinated group develops a more robust coronavirus-specific immune response, with enhanced BCR signaling and metabolic activity compared to the recovered group. These insights might contribute to the optimization of SARS-CoV-2 vaccine design.
SARS-CoV-2感染和疫苗接种都会引发免疫反应。前者导致自然获得性免疫,后者通过人工手段诱导主动免疫。然而,疫苗接种和感染的不同免疫效果及其潜在机制需要进一步澄清。在本研究中,我们比较了接种组和康复组外周血B细胞分化、血清学差异和BCR信号分子表达水平。免疫组表现出rbd特异性B细胞分化减少,记忆B细胞CD86信号强度降低,但B细胞BCR信号增强。在代谢信号方面,接种组pS6、c-Myc、pmTOR和pSTAT5表达水平升高,提示STAT5-c-Myc轴在调节B细胞代谢中发挥作用。此外,蛋白质组芯片分析显示,接种组血清中含有更高水平的针对SARS-CoV-2 N-Nter蛋白的IgG抗体和针对SARS-CoV-2 S1蛋白的IgA抗体。总之,这些发现表明,与康复组相比,接种疫苗组产生了更强大的冠状病毒特异性免疫反应,BCR信号传导和代谢活性增强。这些见解可能有助于优化SARS-CoV-2疫苗的设计。
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引用次数: 0
Thermal tolerance and inactivation of Ebola virus 埃博拉病毒的耐热性和灭活性。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.004
Xiaoxiao Gao, Cheng Peng, Rongjuan Pei
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引用次数: 0
Virome diversity in small mammals from south China: Insights into virus evolution, transmission, and ecology 华南小型哺乳动物的病毒群多样性:对病毒进化、传播和生态学的见解。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.06.004
Yiwei Shi , Letian Fang , Cixiu Li , Peng Li , Jiluo Liu , Yifan Chen , Yue Zhao , Zishuai Li , Shuqi Liu , Yibo Ding , Xinyu Zhou , Dongming Jiang , Jiaying Shen , Zihan Zhang , Junheng Lyu , Rui Pu , Xiaojie Tan , Jianhua Yin , Weifeng Shi , Guangwen Cao
Mammals are critical reservoirs of human infectious diseases and the spillover of viruses is related to climate conditions. We conducted meta-transcriptomic sequencing of 226 mammals (bats, rodents, hedgehogs, and shrews) representing 20 species collected across eight cities in south China between 2018 and 2024. Samples included internal organs, oropharyngeal and anal swabs, and feces. We identified 63 vertebrate-associated viruses, including 34 novel viruses. Phylogenetic analysis revealed six viruses with potential infection risks to humans or domestic animals due to their close phylogenetic relationships with known pathogens. Cross-species transmission was observed in 14.3% (9/63) of viruses, shared by at least two host species, with bats, particularly Rhinolophus and Hipposideros, serving as key hubs for viral circulation and zoonotic spillover. Virome composition varied substantially among mammalian species and geographic regions (adonis test, R2 ​= ​0.50, P ​= ​0.001). Generalized linear models quantified the roles of host taxonomy, ecotypes, and meteorological factors in shaping viral diversity, demonstrating host taxonomy (at the order level) as a predominant role (25.70% deviance explained), followed by ecotypes (10.27% deviance explained). Phylogenetic analysis conducted using our betacoronavirus sequences, as well as betacoronavirus sequences derived from 2.0 ​× ​104 bats sampled in China between July 2013 and March 2024, revealed that no betacoronaviruses exhibited closer phylogenetic relationships to SARS-CoV-2 than the known strains (e.g., RaTG13). These findings provide critical insights into virus evolution, transmission, and ecological determinants, which are essential for the prevention of emerging infectious diseases.
哺乳动物是人类传染病的重要宿主,病毒的外溢与气候条件有关。研究人员对2018年至2024年间在中国南方8个城市收集的226种哺乳动物(蝙蝠、啮齿动物、刺猬和鼩鼱)进行了meta转录组测序。样本包括内脏、口咽和肛门拭子以及粪便。我们鉴定出63种脊椎动物相关病毒,包括34种新型病毒。系统发育分析发现6种病毒与已知病原体有密切的系统发育关系,对人类或家畜具有潜在的感染风险。在14.3%(9/63)的病毒中观察到跨物种传播,至少由两个宿主物种共享,其中蝙蝠,特别是犀牛和希波sideros,是病毒传播和人畜共患溢出的关键枢纽。病毒组组成在哺乳动物种类和地理区域之间存在显著差异(adonis R2 = 0.50, P = 0.001)。广义线性模型量化了宿主分类学、生态型和气象因素在塑造病毒多样性中的作用,表明宿主分类学(在目级)是主要作用(25.70%的偏差解释),其次是生态型(10.27%的偏差解释)。利用我们的冠状病毒序列以及2013年7月至2024年3月在中国采样的2.0 × 104只蝙蝠的冠状病毒序列进行的系统发育分析显示,没有一种冠状病毒与SARS-CoV-2的系统发育关系比已知毒株(例如RaTG13)更密切。这些发现为病毒进化、传播和生态决定因素提供了重要见解,这对预防新发传染病至关重要。
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引用次数: 0
Identification of a novel ectromelia virus from rodent: Implications for use as an in vivo infection model for vaccine and antiviral research 从啮齿动物中鉴定出一种新的鼠爪病毒:用于疫苗和抗病毒研究的体内感染模型的意义。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.001
Shuting Huo , Changcheng Wu , Zhenyong Qi , Jiewei Sun , Xin Meng , Jingdong Song , Zhongxian Zhang , Liye Jin , Chang Shu , Zhifeng Lin , Weibang Huo , Yao Deng , Li Zhao , Jiandong Li , Wenjie Tan
Ectromelia virus (ECTV), a member of the Orthopoxvirus genus, serves as both a causative agent of mousepox and a pivotal surrogate model for studying highly pathogenic orthopoxviruses. Although genomic data on ECTV remains limited, we report the isolation and characterization of a novel strain, ECTV-C-Tan-GD01, obtained from rodents in Guangdong Province, China. Nanopore sequencing yielded a complete genome (199 annotated genes, including one gene truncated at the C-terminus) with inverted terminal repeats (ITRs) harboring a conserved hairpin structure. Notably, a frameshift-inducing “G” deletion in the EV159 gene resulted in the truncation of a semaphorin-like protein. In vitro assays demonstrated cell-associated viral replication kinetics, with maximum titers achieved earlier in Vero/HeLa cells (72 ​h) than in BHK-21/CEF cells (84 ​h). Murine challenge experiments revealed extreme virulence (LD50 ​< ​1 plaque-forming unit (PFU) via intranasal/footpad routes) and hepatosplenic tropism. Furthermore, ECTV-C-Tan-GD01 exhibited utility in evaluating orthopoxvirus countermeasures: a single dose of vaccinia virus Tiantan (VTT) or non-replicating vaccinia virus Tiantan (NTV) conferred cross-protection, while tecovirimat (ST-246), cidofovir (CDV), and brincidofovir (initially CMX001) significantly reduced viral loads and pathology. This study establishes ECTV-C-Tan-GD01 as a dual-purpose resource for probing orthopoxvirus evolution and advancing therapeutic development.
电疣病毒(ECTV)是正痘病毒属的一员,既是小鼠痘的病原体,也是研究高致病性正痘病毒的关键替代模型。虽然关于ECTV的基因组数据仍然有限,但我们报道了从中国广东省啮齿动物中分离和鉴定的一种新菌株ECTV- c - tan - gd01。纳米孔测序得到了一个完整的基因组(199个注释基因,包括一个在c端被截断的基因),其反向末端重复序列(ITRs)包含一个保守的发夹结构。值得注意的是,EV159基因中引起帧移的“G”缺失导致信号蛋白样蛋白的截断。体外实验证实了细胞相关的病毒复制动力学,Vero/HeLa细胞(72小时)比BHK-21/CEF细胞(84小时)更早达到最大滴度。小鼠攻毒实验显示出极强的毒力(LD50 < 1斑块形成单位(PFU),经鼻内/足垫途径)和肝脾性。此外,ECTV-C-Tan-GD01在评估正痘病毒应对措施方面显示出效用:单剂量天坛牛痘病毒(VTT)或非复制性天坛牛痘病毒(NTV)具有交叉保护作用,而tecovirimat (ST-246)、西多福韦(CDV)和brincidofovir(最初为CMX001)可显著降低病毒载量和病理。本研究建立了ECTV-C-Tan-GD01作为探测正痘病毒进化和促进治疗开发的双重资源。
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引用次数: 0
SARS-CoV-2-encoded miR-nsp3-3p promotes pulmonary fibrosis by inhibiting expression of ALCAM sars - cov -2编码的miR-nsp3-3p通过抑制ALCAM的表达促进肺纤维化。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.06.007
Yang Yang , Qiuyue Wu , Xueyan Liu , Hongjian Zhou , Jianzhen Lei , Lan Luo , Xinyi Xia
microRNAs (miRNAs) derived from viruses, have been detected in body fluids and are known to regulate the expression of host genes. Recent evidence indicates that SARS-CoV-2-encoded miRNAs could contribute to pulmonary disease. Pulmonary fibrosis is an important complication in SARS-CoV-2 infected patients, either during hospitalization or after discharge, however, the underlying mechanisms are not fully elucidated. Here, we report a SARS-CoV-2-encoded miRNA, miR-nsp3-3p, facilitates host pulmonary fibrosis by inhibiting expression of activated leukocyte cell adhesion molecule (ALCAM) and promoting epithelial-mesenchymal transition (EMT). First, we detected miR-nsp3-3p in clinical specimens and found it was remarkably increased in throat swabs and alveolar lavage fluids from severe/critical COVID-19 patients compared to control groups or mild/moderate patients. We further revealed that adeno-associated virus (AAV)-nsp3 infection can induce pulmonary fibrosis in BALB/c mice while miR-nsp3-3p antagomirs can reverse that, and ALCAM was found to be as a target gene of miR-nsp3-3p. miR-nsp3-3p overexpression can inhibit the expression of ALCAM and promote EMT of pulmonary epithelial cells. Moreover, overexpression of ALCAM can reverse the miR-nsp3-3p-induced EMT and fibrosis. These findings highlight the essential role of SARS-CoV-2-encoded miRNAs in promoting the pathological progression of lung disease, and provide novel insights into the interactions between viral miRNAs and host pathology.
来自病毒的microrna (miRNAs)已在体液中被检测到,并且已知可调节宿主基因的表达。最近的证据表明,sars - cov -2编码的mirna可能导致肺部疾病。肺纤维化是SARS-CoV-2感染患者住院期间或出院后的重要并发症,但其潜在机制尚未完全阐明。在这里,我们报道了sars - cov -2编码的miRNA miR-nsp3-3p,通过抑制活化的白细胞粘附分子(ALCAM)的表达和促进上皮-间质转化(EMT)来促进宿主肺纤维化。首先,我们在临床标本中检测了miR-nsp3-3p,发现重症/危重患者的咽拭子和肺泡灌洗液中miR-nsp3-3p与对照组或轻/中度患者相比显著增加。我们进一步发现腺相关病毒(adeno-associated virus, AAV)-nsp3感染可诱导BALB/c小鼠肺纤维化,而miR-nsp3-3p拮抗剂可逆转这一现象,并且发现ALCAM是miR-nsp3-3p的靶基因。过表达miR-nsp3-3p可抑制ALCAM的表达,促进肺上皮细胞的EMT。此外,ALCAM过表达可以逆转mir -nsp3-3p诱导的EMT和纤维化。这些发现突出了sars - cov -2编码的mirna在促进肺部疾病病理进展中的重要作用,并为病毒mirna与宿主病理之间的相互作用提供了新的见解。
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引用次数: 0
Issue Cover 覆盖问题
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/S1995-820X(25)00108-7
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引用次数: 0
Single-cycle Rift Valley fever virus particles from stable replicon cells enable discovery of antiviral CNX-1351 for multiple RNA viruses 来自稳定复制子细胞的单循环裂谷热病毒颗粒使多种RNA病毒的抗病毒药物CNX-1351得以发现。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.06.009
Zhichao Gao , Hongyuan Guo , Ziqiao Wang , Pengcheng Wang , Xinran Sun , Shimei Zhang , Fei Feng , Chao Shan , Youhua Xie , Rong Zhang
Rift Valley fever virus (RVFV) is a high-containment pathogen that causes severe diseases in humans, with no approved therapeutics available. Its classification as a biosafety level 3 (BSL-3) agent has limited research and therapeutic development due to safety concerns. In this study, we developed a stable replicon cell line maintaining the replication of L and S genomic segments of RVFV. Single-cycle viral replicon particles (VRPs) could be efficiently packaged through trans-complementation of glycoproteins from different strains, recapitulating authentic viral entry and replication while minimizing biosafety risks. Using this system, we conducted high-throughput screening of a small-molecule compound library and identified CNX-1351 as an antiviral agent for multiple RNA viruses. Mechanistic studies revealed that CNX-1351 inhibits viral replication, potentially by targeting the PI3K-Akt signaling pathway. This single-cycle VRP system provides a valuable tool for studying RVFV biology, host interactions, antiviral and vaccine development under reduced biosafety constraints.
裂谷热病毒(RVFV)是一种高度遏制的病原体,可在人类中引起严重疾病,目前尚无批准的治疗方法。由于安全方面的考虑,它被列为生物安全3级(BSL-3)药物,限制了研究和治疗开发。在这项研究中,我们开发了一种稳定的复制子细胞系,维持RVFV L和S基因组片段的复制。单循环病毒复制子颗粒(VRPs)可以通过不同菌株的糖蛋白的反式互补有效地包装,再现真实的病毒进入和复制,同时最大限度地降低生物安全风险。利用该系统,我们对一个小分子化合物文库进行了高通量筛选,并鉴定出CNX-1351作为多种RNA病毒的抗病毒药物。机制研究表明,CNX-1351可能通过靶向PI3K-Akt信号通路抑制病毒复制。这种单循环VRP系统为研究RVFV生物学、宿主相互作用、在生物安全限制降低的情况下开发抗病毒药物和疫苗提供了有价值的工具。
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引用次数: 0
Isolation and identification of a newly discovered broad-spectrum Acinetobacter baumannii phage and therapeutic validation against pan-resistant Acinetobacter baumannii 新发现的广谱鲍曼不动杆菌噬菌体的分离鉴定及对泛耐药鲍曼不动杆菌的治疗效果验证。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.06.003
Miaomiao Lin , Lele Xiong , Wen Li , Lingyan Xiao , Wei Zhang , Xiaogui Zhao , Yishan Zheng
The treatment of Acinetobacter baumannii (A. baumannii) poses significant clinical challenges due to its multidrug/pan-drug resistance. In this study, we isolated a broad-spectrum lytic A. baumannii phage, named P425, from medical wastewater, targeting nine multidrug-resistant A. baumannii (MDRAB) with diverse capsular types. Biological characterization revealed that P425 maintains activity at pH range of 3–12 and temperature range of 4–50 ​°C. It resists UV irradiation for 20 ​minutes, and had an optimal multiplicity of infection (OMOI) is 0.00001. The adsorption kinetics showed that P425 achieves > 90% within 10 ​minutes of incubation, and the one-step growth curve indicated a 10-min latent period, with a burst size of 184 ​PFU/cell. The genome sequencing results indicated that it harbors a double-stranded DNA genome of 40,583 bp with a GC content of 39.39%. Intergenomic similarity analysis classified it as a novel species within the Friunavirus genus, while electron microscopy results showed that it belongs to the Podoviridae family. Notably, P425 exhibits potent 24-h in vitro inhibitory activity against MDRAB, and demonstrates synergistic effect at an MOI of 0.001 when combined with five classes of antibiotics targeting distinct antimicrobial mechanisms. Safety evaluations confirmed the absence of cytotoxicity, hemolytic activity, or systemic toxicity both in vitro and in vivo. In mouse infection models, P425 can significantly improve the survival rates of mice infected with Ab25 (ST1791/KL101). When co-administered with levofloxacin, it achieved 100% protection against mortality and promoted immune recovery. Collectively, P425 is a prospective lytic phage that could offer novel strategies for combating MDRAB infections.
鲍曼不动杆菌(鲍曼不动杆菌)的多药/泛药耐药给其治疗带来了重大的临床挑战。在这项研究中,我们从医疗废水中分离出一种广谱分解鲍曼尼a.b ummannii噬菌体,命名为P425,靶向9种具有不同荚膜类型的耐多药鲍曼尼a.b ummannii (MDRAB)。生物学特性表明,P425在pH值3 ~ 12、温度4 ~ 50℃范围内保持活性。抗紫外线照射20 min,最佳感染复数(MOI)为0.00001。吸附动力学表明,P425在10 min内达到> 90%,一步生长曲线显示潜伏期为10 min,爆发大小为184 PFU/细胞。基因组测序结果表明,该菌株含有40583 bp的双链DNA基因组,GC含量为39.39%。基因组间相似性分析将其归类为弗鲁纳病毒属的新种,而电子显微镜结果显示它属于足病毒科。值得注意的是,P425对MDRAB表现出强大的24小时体外抑制活性,并且当与五类针对不同抗菌机制的抗生素联合使用时,显示出协同效应,MOI为0.001。安全性评估证实在体内和体外均无细胞毒性、溶血活性或全身毒性。在小鼠感染模型中,P425能显著提高Ab25 (ST1791/KL101)感染小鼠的存活率。当与左氧氟沙星联合使用时,它可以达到100%的死亡率保护并促进免疫恢复。总的来说,P425是一种有前景的裂解噬菌体,可以为对抗MDRAB感染提供新的策略。
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引用次数: 0
Isolation and phylogenetic analysis of swinepox virus from pigs in China 中国猪源猪瘟病毒的分离及系统发育分析。
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.006
Nan Cao , Yamei Li , Xiangmin Li , Ping Qian
{"title":"Isolation and phylogenetic analysis of swinepox virus from pigs in China","authors":"Nan Cao ,&nbsp;Yamei Li ,&nbsp;Xiangmin Li ,&nbsp;Ping Qian","doi":"10.1016/j.virs.2025.07.006","DOIUrl":"10.1016/j.virs.2025.07.006","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 4","pages":"Pages 676-679"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epidemiological and genomic surveillance of influenza A virus (pdm09 H1N1 and H3N2) strains from 2017 to 2025 in Tianjin, China 2017 - 2025年天津市甲型流感病毒(pdm09 H1N1和H3N2)株流行病学和基因组监测
IF 4 3区 医学 Q1 Medicine Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.011
Mingkun Wu , Liru Guo , Mei Kong , Ming Zou , Xiaochang Liu , Xiaoyan Li
Influenza A virus (IAV) remains a global public health concern, causing influenza-like illness and severe respiratory tract infections. Two major subtypes, A/pdm09 H1N1 and A/H3N2, circulate globally, and their epidemics are influenced by multiple factors, especially during the COVID-19 pandemic. Based on data from the National Influenza Surveillance Program in China, we analyzed the epidemiological and genomic data in Tianjin collected from 2017 to 2025. A total of 77,473 throat swabs were collected, of which 9144 were IAV-positive. The A/pdm09 H1N1 and A/H3N2 lineages exhibited distinct epidemics across different influenza seasons, with a decline in cases observed during the COVID-19 pandemic. We sequenced the genomes of 128 A/pdm09 H1N1 and 113 A/H3N2 clinical isolates and characterized their temporal evolution and genetic diversity using time-scaled phylogenetic analysis. Additionally, we conducted a genetic risk evaluation of the hemagglutinin and neuraminidase segments, identifying key amino acid residues associated with viral adaptation, transmissibility, virulence, and drug resistance. Moreover, no antigenic variants were found in clinical isolates during the recent influenza seasons, though reduced sensitivity to oseltamivir and zanamivir was observed in individual strains. Our surveillance highlights the epidemiology and evolution of IAV before and after the COVID-19 pandemic in Tianjin.
甲型流感病毒(IAV)仍然是一个全球公共卫生问题,可引起流感样疾病和严重呼吸道感染。A/pdm09 H1N1和A/H3N2两种主要亚型在全球流行,其流行受多种因素影响,特别是在COVID-19大流行期间。基于中国国家流感监测项目的数据,我们分析了天津市2017 - 2025年的流行病学和基因组学数据。共收集了77473份咽拭子,其中9144份呈iav阳性。A/pdm09 H1N1和A/H3N2谱系在不同的流感季节表现出不同的流行趋势,在COVID-19大流行期间观察到病例数下降。我们对128株A/pdm09 H1N1和113株A/H3N2临床分离株进行了基因组测序,并利用时间尺度的系统发育分析对其时间进化和遗传多样性进行了表征。此外,我们对血凝素和神经氨酸酶片段进行了遗传风险评估,确定了与病毒适应性、传播性、毒力和耐药性相关的关键氨基酸残基。此外,在最近的流感季节,临床分离株中未发现抗原变异,尽管在个别菌株中观察到对奥司他韦和扎那米韦的敏感性降低。我们的监测重点关注天津市COVID-19大流行前后IAV的流行病学和演变。
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引用次数: 0
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Virologica Sinica
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