检索结果-南通市图书馆

New small-molecule drug design strategies for fighting resistant influenza A

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2015年第5期5卷 419-430页

作者： Zuyuan Shen Kaiyan Lou Wei Wang Shanghai Key Laboratory of Chemical Biology School of Pharmacy and State Key Laboratory of Bioengineering Reactor East China University of Science and Technology Department of Chemistry and Chemical Biology University of New Mexico

In fluenza A virus is the major cause of seasonal or pandemic flu worldwide. Two main treatment strategies–vaccination and small molecule anti-in fluenza drugs are currently available. As an effective vaccine usually takes at least 6 months to develop, anti-in fluenza small molecule drugs are more effective for the fi rst line of protection against the virus during an epidemic outbreak, especially in the early stage. Two major classes of anti-in fluenza drugs currently available are admantane-based M2 protein blockers(amantadine and rimantadine) and neuraminidase(NA) inhibitors(oseltamivir, zanamivir, and peramivir). However, the continuous evolvement of in fluenza A virus and the rapid emergence of resistance to current drugs, particularly to amantadine, rimantadine, and oseltamivir, have raised an urgent need for developing new anti-in fluenza drugs against resistant forms of in fluenza A virus. In this review,we fi rst give a brief introduction of the molecular mechanisms behind resistance, and then discuss new strategies in small-molecule drug development to overcome in fluenza A virus resistance targeting mutant M2 proteins and neuraminidases, and other viral proteins not associated with current drugs.

关键词： influenza a virus Drug discovery Resistance M2 ion channel Neuraminidase

Gene Expression Profiles Comparison between 2009 Pandemic and Seasonal H1N1 influenza viruses in A549 Cells

在线全文

学校读者我要写书评

暂无评论

Biomedical and Environmental Sciences 2010年第4期23卷 259-266页

作者： XIAO-XING YANG NING DU JIAN-FANG ZHOU ZI LI MIN WANG JUN-FENG GUO DA-YAN WANG YUE-LONG SHU State Key Laboratory for Molecular Virology and Genetic Engineering National Institute for Viral Disease Control and Prevention China CDC 100 Yingxin Street Xuanwu District Beijing 100052 China

Objective To perform gene expression profiles comparison so that to identify and understand the potential differences in pathogenesis between the pandemic and seasonal A （H1N1） influenza viruses. Methods A549 cells were infected with A/California/07/09 （H1N1） and A/GuangdongBaoan/51/08 （H1N1） respectively at the same MOI of 2 and collected at 2, 4, 8, and 24 h post infection （p.i.）. Gene expression profiles of A549 cells were obtained using the 22 K Human Genome Oligo Array, and differentially expressed genes were analyzed at selected time points. Results Microarrays results indicated that both of the viruses suppressed host immune response related pathways including cytokine production while pandemic H1N1 virus displayed weaker suppression of host immune response than seasonal H1N1 virus. Observation on similar anti-apoptotic events such as activation of apoptosis inhibitor and down-regulation of key genes of apoptosis pathways in both infections showed that activities of promoting apoptosis were different in later stage of infection. Conclusion The immuno-suppression and anti-apoptosis events of pandemic H1N1 virus were similar to those seen by seasonal H1N1 virus. The pandemic H1N1 virus had an ability to inhibit biological pathways associated with cytokine responses, NK activation and macrophage recognition .

关键词： influenza a virus Pandemic H1N1 A549 Expression profiling array

mpaired NK cell antiviral cytokine response against nfluenza virus in small-for-gestational-age neonates

在线全文

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2013年第5期10卷 437-443页

作者： Jinrong Li Hong Li Huawei Mao Meixing Yu Fan Yang Ting Feng Yingying Fan Qiao Lu Chongyang Shen Zhongwei Yin Meng Mao Wenwei Tu The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong Sichuan University Chengdu China Department of Pediatric West China Second University Hospital Sichuan University Chengdu China Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital Sichuan University Chengdu China Department of Pediatrics & Adolescent Medicine Li Ka Shing Faculty of Medicine University of Hong Kong Pokfulam Hong Keng SAR. China These authors contributed equally to this work

The neonates, particularly small-for-gestational-age （SGA） ones, are susceptible to various microbial infections. Natural killer （NK） cells are critical components of host innate immunity system and the main source of the inflammatory cytokines, which provide critical protection during the early phase of viral infections before the development of an appropriate adaptive immune response. However, little is known about the antiviral effects of NK cells in neonates especially the SGA population. Herein, a prospective descriptive study was performed to determine the differences of NK cell immunity among adults, appropriate-for gestational-age （AGA） and SGA neonates. Adults have much higher NK cell number in peripheral blood than that in cord blood from neonates. In response to influenza virus stimulation, neonatal NK cells, especially SGA baby cells, expressed significantly lower antiviral cytokines including perforin, interferon （IFN）-7 and tumor-necrosis factor （TNF）-α responses than adult NK cells. In addition, the antiviral cytokine responses of NK cells were positively correlated with neonatal birth weight. Our data suggested that the depressed antiviral activity and less frequency of NK cells are likely to be responsible for the high susceptibility to microbial infection in neonates, at least in part. Improving the function of innate immunity may provide a new way to defend virus infection.

关键词： influenza a virus neonates NK cells SGA

Vγ9Vδ2-T lymphocytes have impaired antiviral function in small-for-gestational-age and preterm neonates

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2013年第3期10卷 253-260页

作者： Jinrong Li Hong Li Huawei Mao Meixing Yu Ting Feng Fan Yang Yingying Fan Qiao Lu Chongyang Shen Zhongwei Yin Wenwei Tu Meng Mao The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong Chengdu China Department of Pediatric West China Second University Hospital Sichuan University Chengdu China Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital Sichuan University Chengdu China Department of Pediatrics & Adolescent Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China These authors contributed equally to this work.

Preterm and small-for-gestational-age （SGA） neonates are vulnerable groups that are susceptible to various microbial infections. Vγ9Vδ2-T cells are critical components of the host immune system and have been demonstrated to play an important role in the defense against viral infection in adults. However, the characteristics of Vγ9Vδ2-T cells in children, especially the preterm and SGA populations, are poorly understood. Here, we examined the frequency and antiviral function of Vγ9Vδ2-T cells in neonates, including preterm, SGA and full-term babies. When compared to adults, neonates had a significantly lower percentage of Vγ9Vδ2-T cells in the blood. Upon influenza virus stimulation, neonatalVγ9Vδ2-T cells, especially from preterm and SGA babies, showed markedly decreased and delayed antiviral cytokine responses than those of adults. In addition, the antiviral responses of neonatal Vγ9Vδ2-T cells were positively correlated with gestational age and birth weight. Finally, a weaker expansion ofVγ9Vδ2-T cells by isopentenyl pyrophosphate （IPP） was shown in neonates than the expansion in adults. Our data suggest that the depressed antiviral activity and decreased frequency of Vγ9Vδ2-T cells may likely account for the high susceptibility to microbial infection in neonates, particularly in preterm and SGA babies. Improving Vγ9Vδ2-T -cell function of neonates may provide a new way to defend against virus infection.

关键词： cord blood influenza a virus preterm small for gestational age Vγ9Vδ2 T cell

Human Vγ9Vδ2-T cells efficiently kill influenzavirus-infected lung alveolar epithelial cells

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2013年第2期10卷 159-164页

作者： Hong Li Zheng Xiang Ting Feng Jinrong Li Yinping Liu Yingying Fan Qiao Lu Zhongwei Yin Meixing Yu Chongyang Shen Wenwei Tu joint Research Center of West China Second University Hospital of Sichuan University and Department of Paediatrics and Adolescent Medicine of University of Hong Kong Sichuan University Chengdu 610041 China Department of Paediatrics and Adolescent Medicine University of Hong Kong Hong Kong China HL and ZX contributed equally to this study

γδ-T cells play an indispensable role in host defense against different viruses, including influenza a virus. However, whether these cells have cytotoxic activity against influenza virus-infected lung alveolar epithelial cells and subsequently contribute to virus clearance remains unknown. Using influenza virus-infected A549 cells, human lung alveolar epithelial cells, we investigated the cytotoxic activity of aminobisphosphonate pamidronate （PAM）-expanded human Vγ9Vδ2-T cells and their underlying mechanisms. We found that PAM could selectively activate and expand human Vγ9Vδ2-T cells. PAM-expanded human Vγ9Vδ2-T cells efficiently killed influenza virus-infected lung alveolar epithelial cells and inhibited virus replication. The cytotoxic activity of PAM-expanded Vγ9Vδ2-T cells was dependent on cell-to-cell contact and required NKG2D activation. Perforin-granzyme B, tumor-necrosis factor-related apoptosis-inducing ligand （TRAIL） and Fas-Fas ligand （FasL） pathways were involved in their cytotoxicity. Our study suggests that targeting γδ2-T cells by PAM can potentially offer an alternative option for the treatment of influenza virus.

关键词： A549 cells influenza a virus PAM Vγ9Vδ2 T cell

TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Protein & Cell 2020年第12期11卷 894-914页

作者： Nan Sun Li Jiang Miaomiao Ye Yihan Wang Guangwen Wang Xiaopeng Wan Yuhui Zhao Xia Wen Libin Liang Shujie Ma Liling Liu Zhigao Bu Hualan Chen Chengjun Li State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Tripartite motif(TRIM)family proteins are important effectors of innate immunity against viral infections.Here we identified TRIM35 as a regulator of TRAF3 activation.Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon(IFN)in response to viral infection.777m35-deficient mice were more susceptible to influenza a virus(IAV)infection than were wild-type mice.TRIM35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1.IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3.TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2,thereby antagonizing its suppression of TRAF3 activation.Our in vitro and in vivo findings thus reveal novel roles of TRIM35,through catalyzing Lys63-or Lys48-linked polyubiquitination,in RIG-I antiviral immunity and mechanism of defense against IAV infection.

关键词： influenza a virus PB2 TRIM35 TRAF3 ubiquitination antiviral immunity

Possible Impact of Global Warming on the Evolution of Hemagglutinins from influenza a viruses

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Biomedical and Environmental Sciences 2011年第1期24卷 62-67页

作者： YAN ShaoMin WU Guang National Engineering Research Center for Non-food Biorefinery Guangxi Academy of Sciences Nanning 530007 Guangxi China Computational Mutation Project DreamSciTech Consulting Shenzhen 518054 Guangdong China

Objective To determine if global warming has an impact on the evolution of hemagglutinins from influenza a viruses, because both global warming and influenza pandemics/epidemics threaten the world. Methods 4 706 hemagglutinins from influenza a viruses sampled from 1956 to 2009 were converted to a time-series to show their evolutionary process and compared with the global, northern hemisphere and southern hemisphere temperatures, to determine if their trends run in similar or opposite directions. Point-to-point comparisons between temperature and quantified hemagglutinins were performed for all species and for the major prevailing species. Results The comparisons show that the trends for both hemagglutinin evolution and temperature change run in a similar direction. Conclusion Global warming has a consistent and progressive impact on the hemagglutinin evolution of influenza a viruses.

关键词： Evolution Global warming Hemagglutinin influenza a virus Mutation

Induction of innate immunity and its perturbation by influenza viruses

在线全文

学校读者我要写书评

暂无评论

Protein & Cell 2015年第10期6卷 712-721页

作者： Mohsan Ullah Goraya Song Wang Muhammad Munir Ji-Long Chen College of Animal Science Fujian Agriculture and Forestry University Fuzhou 350002 China The Pirbright Institute Ash Road Pirbright Woking GU24 0NF UK CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China

influenza a viruses （IAV） are highly contagious patho- gens causing dreadful losses to human and animal, around the globe. IAVs first interact with the host through epithelial cells, and the viral RNA containing a 5＇-triphosphate group is thought to be the critical trigger for activation of effective innate immunity via pattern recognition receptors-dependent signaling pathways. These induced immune responses establish the antiviral state of the host for effective suppression of viral replication and enhancing viral clearance. However, IAVs have evolved a variety of mechanisms by which they can invade host cells, circumvent the host immune responses, and use the machineries of host cells to synthesize and transport their own components, which help them to establish a successful infection and repli- cation. In this review, we will highlight the molecular mechanisms of how IAV infection stimulates the host innate immune system and strategies by which IAV evades host responses.

关键词： influenza a virus innate immunity immuneescape

influenza A （H1N1） pneumonia： an analysis of 63 cases by chest CT

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 2011年第17期124卷 2669-2673页

作者： LI Min ZHU Jian-bing CHEN Guang-qiang YANG Wei-ye TAO Cheng WANG Xiao-hui Department of Radiology Fifth People's Hospital of Suzhou Suzhou Jiangsu 215000 China Department of Radiology Second Affiliated Hospital of Soochow University Suzhou Jiangsu Department of Radiology University of Pittsburgh Pittsburgh 15213 USA

Background In early April 2009, cases of human infection with 2009 pandemic influenza A （H1N1） virus were identified in Mexico. The virus then spread rapidly to other regions of the world. From October 2009, sporadic imported cases of novel influenza A （HIN1） were continuously confirmed in Suzhou. The aim of the study was to review the chest CT findings in 63 patients with laboratory-confirmed novel swine-origin influenza A （H1N1） virus （S-OIV） infection. Methods Chest CT examinations were collected from 63 S-OIV infected patients during their hospital stay. Three experienced radiologists inspected images to qualitatively and quantitatively characterize S-OIV induced image changes. CT scores of lesion severity were calculated based on the percentage of affected area to determine severity of infectious lesions. Patients were divided into two groups based on the leukocyte counts. Lesion patterns, local distributions, and quantitative measures were investigated and compared between the two groups. Results Various degrees of bilateral multifocal lesions of ground-glass opacities were found with or without consolidations on the chest CT images. The lesions were both bronchocentric and centrilobular. Patients with elevated leukocyte counts had more extensive lesions, in terms of severity and affected area, than the patients with normal leukocyte counts. The lesion severity scores of patients in the elevated leukocyte group were significantly higher than those of the normal leukocyte group in terms of the entire lung area （P 〈0.01）, and upper （P 〈0.05） and lower （P 〈0.01） lobes as well. There were changes in the CT characteristics seen at follow-up as demonstrated by lesions absorption （P 〈0.01）, especially in the upper lobe of the lung （P〈0.01）, but less so in the middle lobe/lingual and lower lobe of the lung （m〉o.o5）. Conclusions The most common CT findings in S-OIV infection patients were bilateral multifocal distributed ground-glass opacities and consolidations. The lesions were located dominantly at bronchocentric

关键词： influenza a virus H1N1 subtype pneumonia tomography X-ray computed