检索结果-南通市图书馆

M6PR interacts with the HA2 subunit of Influenza A virus to facilitate the fusion of viral and endosomal membranes

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Science China(Life Sciences) 2024年第3期67卷 579-595页

作者： Yuzhen Hu Li Jiang Guangwen Wang Yangming Song Zhibo Shan Xuyuan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Liling Liu Hualan Chen Chengjun Li State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.

关键词： Influenza A virus M6PR HA membrane fusion late endosome

Influenza A virus use of BinCARD1 to facilitate the binding of viral NP to importinα7 is counteracted by TBK1-p62 axis-mediated autophagy

在线全文

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2022年第10期19卷 1168-1184页

作者： Xuyuan Wang Li Jiang Guangwen Wang Wenjun Shi Yuzhen Hu Bo Wang Xianying Zeng Guobin Tian Guohua Deng Jianzhong Shi Liling Liu Chengjun Li Hualan Chen College of Veterinary Medicine Gansu Agricultural UniversityLanzhou730070China Guangdong Laboratory for Lingnan Modern Agriculture Guangzhou510642China State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin150069China

As a major component of the viral ribonucleoprotein(vRNP)complex in Influenza A virus(IAV),nucleoprotein(NP)interacts with isoforms of importinαfamily members,leading to the import of itself and vRNP complex into the nucleus,a process pivotal in the replication cycle of IAV.In this study,we found that BinCARD1,an isoform of Bcl10-interacting protein with CARD(BinCARD),was leveraged by IAV for efficient viral replication.BinCARD1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex activity.Moreover,we found that BinCARD1 interacted with NP to promote NP binding to importinα7,an adaptor in the host nuclear import pathway.However,we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3,and that TBK1 appeared to degrade BinCARD1.We showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage,which was recognized by the TBK1-p62 axis for autophagic degradation.Overall,our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication,and two mechanisms in the host defense system are triggered—innate immune signaling and autophagic degradation—to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.

关键词： Influenza A virus BinCARD1 TRAF3 TBK1 p62

Generation and application of two monoclonal antibodies targeting conserved linear epitopes in the NP protein of Influenza A virus

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Integrative Agriculture 2022年第7期21卷 2095-2105页

作者： ZHAO Yu-hui WEN Xia LI Qi-bing JIANG Li WANG Guang-wen LIANG Li-bin WANG Xiu-rong CHEN Hua-lan LI Cheng-jun State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069P.R.China

Monoclonal antibodies(mAbs) are widely used in virus research and disease diagnosis. The nucleoprotein(NP) of Influenza A virus(IAV) plays important roles in multiple stages of the virus life cycle. Therefore, generating conserved mAbs against NP and characterizing their properties will provide useful tools for IAV research. In this study, two mAbs against the NP protein, 10 E9 and 3 F3, were generated with recombinant truncated NP proteins(NP-1 and NP-2) as immunogens. The heavy-chain subclass of both 10 E9 and 3 F3 was determined to be IgG2α, and the light-chain type was κ. Truncation and site-specific mutation analyses showed that the epitopes of mAbs 10 E9 and 3 F3 were located in the N terminal 84–89 amino acids and the C terminal 320–324 amino acids of the NP protein, respectively. We found that mAbs 10 E9 and 3 F3 reacted well with the NP protein of H1–H15 subtypes of IAV. Both 10 E9 and 3 F3 can be used in immunoprecipitation assay, and 10 E9 was also successfully applied in confocal microscopy. Furthermore, we found that the 10 E9-recognized _(84) SAGKDP_(89) epitope and 3 F3-recognized 320 ENPAH324 epitope were highly conserved in NP among all avian and human IAVs. Thus, the two mAbs we developed could be used as powerful tools in the development of diagnostic methods of IAV, and also surely promote the basic research in understanding the replication mechanisms of IAV.

关键词： Influenza A virus nucleoprotein monoclonal antibody application

Discovery of the anti-Influenza A virus activity of SB216763 and cyclosporine A by mining infected cells and compound cellular signatures

在线全文

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2022年第5期33卷 2541-2544页

作者： Ke Tang You Wu Shubing Chen Yijing Xin Ying Guo State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of Pharmacology Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

In this study,SB216763 and cyclosporine A were identified as anti-Influenza A virus(IAV)agents by tran-scriptome signature reversion(TSR)analysis through deep mining of the cellular transcriptome of hu-man airway and lung cell lines infected with 3 strains of IAV and the chemical perturbations library.A synergistic effect of SB216763 and cyclosporine A against influenza A was disclosed by quantification of the network-based relationship,which was validated in vitro.Along with burgeoning omics approaches,transcriptome-based drug development is flourishing,which provides a novel insight into antivirals dis-covery with comprehensive cellular transcriptional information of disease and chemical perturbations in multicomponent intervention.This strategy can be applied as a new approach in discovering multitar-get antiviral agents from approved drugs,clinical compounds,natural products or other known bioactive compounds.

关键词： Chemical perturbagen signature Host factor Transcriptome signature reversion Influenza A virus SB216763 Cyclosporine A Drug combination

Cytokine Profiling in Influenza A virus and Staphylococcal(Co-)Infections

在线全文

学校读者我要写书评

暂无评论

Infectious Microbes & Diseases 2022年第4期4卷 161-167页

作者： Lea A.Tölken Antje D.Paulikat Fabian Cuypers Sebastian B.Skorka Sven Hammerschmidt Nikolai Siemens Department of Molecular Genetics and Infection Biology Interfaculty Institute for Genetics and Functional GenomicsCenter for Functional Genomics of MicrobesUniversity of GreifswaldGreifswaldGermany

Influenza A virus and Staphylococcus aureus are common causative agents of pneumonia.Co-infections with these two pathogens frequently occur and are characterized,among others,by higher morbidity and mortality due to hyper-inflammation of the lungs.Here,we aimed to profile systemic and local cytokine composition at early acute stages of pneumonia in amurinemodel.Allmice recovered from single Influenza A virus and/or staphylococcal infections.In contrast,co-infections led to a severe clinical outcome.While distinct cytokine patterns were detected in lungs of single-pathogen-infected animals,co-infections combined both virus-and bacteria-driven responses.However,analyses of infected human primarymonocytic cells as well as bronchial epithelial cells did not reflectmurine profiles.Based on infectious dose,mainly bacteria-driven responses were noted.The impact of single cells to cytokine composition of the lungs and translation of murine studies to humans remains uncertain and warrants further studies.

关键词： Influenza A virus Staphylococcus aureus co-infection cytokines

Down-regulation of miR-155 inhibits inflammatory response in human pulmonary microvascular endothelial cells infected with Influenza A virus by targeting sphingosine-1-phosphate receptor 1

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Medical Journal 2020年第20期133卷 2429-2436页

作者： Si-Mei Shen Hao Jiang Jiang-Nan Zhao Yi Shi Department of Respiratory and Critical Care Medicine Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu 210016China Department of Emergency Medicine The Second Affiliated HospitalSoutheast UniversityNanjingJiangsu 210003China

Background:Endothelial cells play a key role in the cytokine storm caused by Influenza A virus. MicroRNA-155 (miR-155) is an important regulator in inflammation. Its role in the inflammatory response to influenza A infection, however, has yet to be elucidated. In this study, we explored the role as well as the underlying mechanism of miR-155 in the cytokine production in influenza A-infected endothelial cells.Methods:Human pulmonary microvascular endothelial cells (HPMECs) were infected with the Influenza A virus strain H1N1. The efficiency of H1N1 infection was confirmed by immunofluorescence. The expression levels of proinflammatory cytokines and miR-155 were determined using real-time polymerase chain reaction. A dual-luciferase reporter assay characterized the interaction between miR-155 and sphingosine-1-phosphate receptor 1 (S1PR1). Changes in the target protein levels were determined using Western blot analysis.Results:MiR-155 was elevated in response to the H1N1 infection in HPMECs (24 h post-infection vs. 0 h post-infection, 3.875 ± 0.062 vs. 1.043 ± 0.013, P = 0.001). Over-expression of miR-155 enhanced inflammatory cytokine production (miR-155 mimic vs. negative control, all P influenza A-induced inflammatory response by targeting S1PR1.

关键词： MicroRNA-155 Sphingosine 1-phosphate receptor 1 Influenza A virus Endothelial cells

Nucleoprotein phosphorylation site(Y385)mutation confers temperature sensitivity to Influenza A virus due to impaired nucleoprotein oligomerization at a lower temperature

在线全文

学校读者我要写书评

暂无评论

Science China(Life Sciences) 2021年第4期64卷 633-643页

作者： Weinan Zheng Liang Cui Minghui Li Yun Li Wenhui Fan Limin Yang Jing Li Lei Sun Wenjun Liu CAS Key Laboralory of Pathogenic Microbiology and Immumology Institute of MicrobiologyChinese Academy of SciencesBejing 100101China University of Chinese Academy of Sciences Bejing 100101China State Key Laboratory for Conservation and Urilization of Subtropical Agro-Bioresourses&Laboratory of Animal Infectious Diseases College of Animal Sciences and Veterinary MedicineGuangxi UniversitNanning 530004China Instinute of Microbiology Center for Biosafety Mega-ScienceChinese Academy of SciencesBeijing 100101China

Mutations in viral proteins can lead to the cold adaption of Influenza A virus and the cold-adapted virus is an important vaccination instrument.Here,we identify a novel strain of Influenza A virus with cold sensitivity conferred by a mutation at a phosphorylation site within the nucleoprotein(NP).The highly conserved tyrosine 385 residue(Y385)of NP was identified as a phosphorylation site by mass spectrometry.The constructive NP phosphorylation mimicked by Y385 E mutation was fatal for virus replication,while the continuous Y385 dephosphorylation mimicked by Y385 F mutation had little impact on virus replication in vitro.Notably,the Y385 F virus showed much lower replicative capacity in turbinates of mice compared with the wild type virus.Moreover,the replication of Y385 F virus was significantly reduced in both A549 and MDCK cells grown at 33℃,when compared to that at 37℃.These results indicated that the Y385 F mutation led to cold sensitivity of virus.We further found that the cold sensitivity of Y385 F virus could be attributed to diminished NP oligomerization rather than any changes in intracellular localization.Taken together,these findings suggest that the phosphorylation of NP may be a critical factor that regulates the temperature sensitivity of Influenza A virus.

关键词： Influenza A virus nucleoprotein phosphorylation dephosphorylation temperature sensitivity

Chinese herbal medicine compound Yi-Zhi-Hao pellet inhibits replication of influenza virus infection through activation of heme oxygenase-1

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2017年第6期7卷 630-637页

作者： Jinqiu Yin Linlin Ma Huiqiang Wang Haiyan Yan Jin Hu Wen Jiang Yuhuan Li Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College School of Medical Technology Shanghai University of Medicine and Health Sciences Department of Pharmacy The Sixth Affiliated Hospital of Xinjiang Medical University

As a leading cause of respiratory disease, Influenza A virus(IAV) presents a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapies, there remains to be a requirement for new drugs. Compound Yi-Zhi-Hao pellet(CYZH) is a famous traditional Chinese medicine(TCM) used in the clinic, whose formula has been recorded in Complication of National Standard for Traditional Chinese Medicine to treat common cold. In this study, we found that CYZH exhibited a broad-spectrum anti-influenza activity and inhibited the expression of viral RNA and proteins in vitro. Mechanistically, CYZH had no inhibitory activities against viral protein hemagglutinin and IAV RNA-dependent RNA polymerase. Instead, it induced activation of erythroid 2-related factor 2(Nrf2) and nuclear factor kappa B(NF-κB), which subsequently upregulated heme oxygenase-1(HO-1) expression.Also, CYZH protected cells from oxidative damage induced by reactive oxygen series. In conclusions,CYZH inhibits IAV replication in vitro, at least partly by activating expression of the Nrf2/HO-1 pathway.

关键词： TMC Influenza A virus Heme oxygenase 1 Hemagglutinin Nrf2 NF-κB

Evaluation of A Single-reaction Method for Whole Genome Sequencing of Influenza A virus using Next Generation Sequencing

在线全文

学校读者我要写书评

暂无评论

Biomedical and Environmental Sciences 2016年第1期29卷 41-46页

作者： Zou Xiao Hui Chen Wen Bing Zhao Xiang Zhu Wen Fei Yang Lei Wang Da Yan Shu Yue Long chinese national influenza center national institute for viral disease control and preventionchina cdckey laboratory for medical virologyministry of healthBeijing 102206China

Objective To evaluate a single-reaction genome amplification method, the multisegment reverse transcription-PCR （M-RTPCR）, for its sensitivity to full genome sequencing of Influenza A virus, and the ability to differentiate mix-subtype virus, using the next generation sequencing （NGS） platform. Methods virus genome copy was quantified and seria（iy diluted to different titers, followed by amplification with the M-RTPCR method and sequencing on the NGS platform. Furthermore, we manually mixed two subtype viruses to different titer rate and amplified the mixed virus with the M-RTPCR protocol, followed by whole genome sequencing on the NGS platform. We also used clinical samples to test the method performance. Results The M-RTPCR method obtained complete genome of testing virus at 125 copies/reaction and determined the virus subtype at titer of 25 copies/reaction. Moreover, the two subtypes in the mixed virus could be discriminated, even though these two virus copies differed by 200-fold using this amplification protocol. The sensitivity of this protocol we detected using virus RNA was also confirmed with clinical samples containing Iow-titer virus. Conclusion The M-RTPCR is a robust and sensitive amplification method for whole genome sequencing of Influenza A virus using NGS platform.

关键词： Influenza A virus Whole genome sequencing NGS