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Influenza virus H1N1 induced apoptosis of mouse astrocytes and the effect on protein expression

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Asian Pacific Journal of Tropical Medicine 2014年第7期7卷 572-575页

作者： Xu-Dong Pei Yu-Feng Zhai Huai-Hong Zhang Department of Infection and Liver Disease Nanyang Central Hospital

Objective:To investigate the effects of influenza A virus H1N1 infection on the proliferation and apoptosis of mouse astrocytes cells and its protein expression.Methods:After mouse astrocytes was infected with purified influenza A virus H1N1 in vitro,viral integration and replication status of the cells were detected by RT-PCR assay,cell proliferation and apoptosis was determined by MTT method and flow cytometry,respectively.Associated protein expression was delected by Western blotting.Results:Agarose gel electrophoresis showed H1N1 virus can infect astrocytes and can be copied.MTT staining showed H1N1 virus infection can inhibit the proliferation of mouse astrocytes,which makes cell viability decreased significantly.Flow cytometry showed that the proportion of Annein V staining positive vascular endothelial cells in the influenza A virus group was significantly higher than that in the control group.Western blot analysis showed after24 h and 32 h of infection,there were cells caspase-3 protein and the expression of its active form(lysed caspase-3 protein)increased.The proportion of Bax/Bcl-2 also increased.Conclusions:Influenza A virus can infect human vascular endothelial cells and proliferation and it can induce apoptosis of endothelial cells.

关键词： Influenze virus H1N1 Apoptosis

Clinical features and treatment outcomes of human immunodeficiency virus-associated cryptococcal meningitis:a 2-year retrospective analysis

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Chinese Medical Journal 2020年第23期133卷 2787-2795页

作者： Wei Song Yin-Zhong Shen Zhen-Yan Wang Tang-Kai Qi Li Liu Ren-Fang Zhang Jiang-Rong Wang Yang Tang Jun Chen Jian-Jun Sun Hong-Zhou Lu Department of Infection and Immunity Shanghai Public Health Clinical CenterFudan UniversityShanghai 201508China

Background:Cryptococcal meningitis(CM)is one of the most common opportunistic infections caused by Cryptococcus neoformans in human immunodeficiency virus(HIV)-infected patients,and is complicated with significant morbidity and mortality.This study retrospectively analyzed the clinical features,characteristics,treatment,and outcomes of first-diagnosed HIV-associated CM after 2-years of follow-up.Methods:Data from all patients(n=101)of HIV-associated CM hospitalized in Shanghai Public Health Clinical Center from September 2013 to December 2016 were collected and analyzed using logistic regression to identify clinical and microbiological factors associated with mortality.Results:Of the 101 patients,86/99(86.9%)of patients had CD4 countinfection with PCP on admission(adjusted odds ratio[AOR],3.933;95%confidence interval[CI],1.166-13.269,P=0.027)and altered mental status(AOR,9.574;95%CI,2.548-35.974,P=0.001)were associated with higher mortality at 8 weeks.Conclusion:This study described the clinical features and outcomes of first diagnosed HIV-associated CM with 2-year follow-up data.Altered mental status and coinfection with PCP predicted mortality in HIV-associated CM.

关键词： Clinical features Cryptococcal meningitis HIV Intracranial lesions Mortality

Clinical outcomes of people living with human immunodeficiency virus(HIV)with diffuse large B-cell lymphoma(DLBCL)in Shanghai,China

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Chinese Medical Journal 2020年第23期133卷 2796-2802页

作者： Jian-Jun Sun Li Liu Jiang-Rong Wang Yin-Zhong Shen Tang-Kai Qi Zhen-Yan Wang Yang Tang Wei Song Jun Chen Ren-Fang Zhang Department of Infection and Immunity Shanghai Public Health Clinical CenterFudan UniversityShanghai 201508China

Background:Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus(HIV).However,little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV(PLHIV).Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide,prednisone,vincristine,cyclophosphamide,doxorubicin,and rituximab(DA-EPOCH-R)with standard cyclophosphamide,doxorubicin,vincristine,prednisone and rituximab(R-CHOP)as front line therapy for PLHIV with diffuse large B-cell lymphoma(DLBCL)receiving modern combined antiretroviral therapy(cART).Methods:A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019.The demographic and clinical data were collected,and overall survival(OS)and progression-free survival(PFS)analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis.Additionally,a Cox multiple regression model was constructed to identify related factors for OS.Results:A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months(interquartile range[IQR]:8-29 months).The proportion of high international prognostic index(IPI)patients was much larger in the DA-EPOCH-R group(n=29)than that in the R-CHOP group(n=25).The CD4 cell counts and HIV RNA levels were not significantly different between the two groups.The 2-year OS for all patients was 73%.However,OS was not significantly different between the two groups,with a 2-year OS rate of 78%for the DA-EPOCH-R group and 66%for the R-CHOP group.Only an IPI greater than 3 was associated with a decrease in OS,with a hazard ratio of 5.0.The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups.Conclusions:Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy.No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART er

关键词： Diffuse large B-cell lymphoma HIV infection Overall survival Progression free survival

Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H 1N 1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice

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Cellular & Molecular Immunology 2017年第6期14卷 511-520页

作者： I-Na Lu Sophie Farinelle Aurelie Sausy Claude P Muller Department of Infection and Immunity Luxembourg Institute of Health Esch-sur-Alzette L-4354 Luxembourg

The stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain, which makes it a potential target for use as a universal vaccine against influenza. However, the role of CD4 T cells in the hemagglutinin stalk-specific immune response is not clear. Here we identified a mouse CD4 T-cell epitope that encompasses residues HA2113-131 from the hemagglutinin stalk domain after a sub-lethal infection of influenza. In response to stimulation with the identified epitope, splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2, TNF-a and IFN-7 production as well as degranulation. Moreover, mice immunized with the peptide corresponding to this CD4 T-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor I~ sequences, and they had a higher survival rate following a challenge with a lethal dose of pandemic H IN 1 influenza virus. Thus, our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 T cells in the host immune resoonse a^ainst influenza virus infection.

关键词： H1N1 hemagglutinin influenza T-cell receptor

Outlook on the gut microbiota

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Gastroenterology Report 2022年第1期10卷 1-2页

作者： Bjoern O.Schroeder department of Molecular Biology UmeaUniversityUmeaSweden Laboratory for Molecular infection Medicine Sweden(MIMS) UmeaUniversityUmeaSweden

Despite being a rather young research field that only emerged in the last two decades,it has become clear that the gut microbiota is an essential part of our body that strongly influences the processes that regulate our health and wellbeing.In this Special Issue of Gastroenterology Report,we have compiled a collection of articles which discuss that microbial signals deriving from our internal bioreactor are by no means restricted to the gut environment,and why it is thus reasonable to consider the gut microbial community as an additional organ to our body.

关键词： Outlook spite restricted

Interventions pathways to reduce tuberculosis-related stigma:a literature review and conceptual framework

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Infectious Diseases of Poverty 2022年第5期11卷 90-90页

作者： Charlotte Nuttall Ahmad Fuady Holly Nuttall Kritika Dixit Muchtaruddin Mansyur Tom Wingfeld department of Clinical infection Microbiology and ImmunologyUniversity of LiverpoolLiverpoolUK 不详

Background:Prevention of tuberculosis(TB)-related stigma is vital to achieving the World Health Organisation’s End TB Strategy target of eliminating TB.However,the process and impact evaluation of interventions to reduce TB-stigma are limited.This literature review aimed to examine the quality,design,implementation challenges,and successes of TB-stigma intervention studies and create a novel conceptual framework of pathways to TB-stigma reduction.Method:We searched relevant articles recorded in four scientifc databases from 1999 to 2022,using pre-defned inclusion and exclusion criteria,supplemented by the snowball method and complementary grey literature searches.We assessed the quality of studies using the Crowe Critical Appraisal Tool,then reviewed study characteristics,data on stigma measurement tools used,and interventions implemented,and designed a conceptual framework to illustrate the pathways to TB-stigma reduction in the interventions identifed.Results:Of 14,259 articles identifed,eleven met inclusion criteria,of which three were high quality.TB-stigma reduction interventions consisted mainly of education and psychosocial support targeted predominantly toward three key populations:people with TB,healthcare workers,and the public.No psychosocial interventions for people with TB set TB-stigma reduction as their primary or co-primary aim.Eight studies on healthcare workers and the public reported a decrease in TB-stigma attributed to the interventions.Despite the benefts,the interventions were limited by a dearth of validated stigma measurement tools.Three of eight studies with quantitative stigma measurement questionnaires had not been previously validated among people with TB.No qualitative studies used previously validated methods or tools to qualitatively evaluate stigma.On the basis of these fndings,we generated a conceptual framework that mapped the population targeted,interventions delivered,and their potential efects on reducing TB-stigma towards and experienced by people with TB and healthcare work

关键词： Tuberculosis Stigma Intervention Stigma measurement tool

Omicron spike protein:a clue for viral entry and immune evasion

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3639-3640页

作者： G.M.N.Behrens A.Cossmann M.Hoffmann department for Rheumatology and Immunology Hannover Medical SchoolHannoverGermany German Centre for infection Research partner site Hannover-BraunschweigHannoverGermany CiiM Centre for Individualized Infection MedicineHannoverGermany infection Biology Unit German Primate CenterGöttingen 37077Germany Faculty of Biology and Psychology Georg-August-University GöttingenGöttingenGermany

In a recent study in Science,Bowen et al.1 report that mutations in Omicron sublineage’s spike protein enhance ACE2 binding,impair fusogenicity,and dampen the neutralizing activity of antibodies after vaccination or infection.The data describe how Omicron and especially the BA.5 variant evade neutralizing antibody responses and argue for using mRNA booster vaccination to increase immunity.

关键词： ACE2 Bowen al.

Ubiquitin-specific protease 24 promotes EV71 infection by restricting K63-linked polyubiquitination of TBK1

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Virologica Sinica 2023年第1期38卷 75-83页

作者： Lichao Zang Jin Gu Xinyu Yang Yukang Yuan Hui Guo Wei Zhou Jinhong Ma Yan Chen Yumin Wu Hui Zheng Weifeng Shi department of Laboratory Medicine The Third Affiliated Hospital of Soochow UniversityChangzhou213003China International Institute of infection and Immunity Institutes of Biology and Medical SciencesSoochow UniversitySuzhou215123China Jiangsu Key Laboratory of infection and Immunity Soochow UniversitySuzhou215123China Hubei Hospital of Integrated Chinese and Western Medicine Wuhan430015China

TANK-binding kinase 1(TBK1)is an essential protein kinase for activation of interferon regulatory factor 3(IRF3)and induction of the type I interferons(IFN-I).Although the biochemical regulation of TBK1 activation has been studied,little is known about how enterovirus 71(EV71)employs the deubiquitinases(DUBs)to regulate TBK1 activation for viral immune evasion.Here,we found that EV71 infection upregulated the expression of ubiquitinspecific protease 24(USP24).Further studies revealed that USP24 physically interacted with TBK1,and can reduce K63-linked polyubiquitination of TBK1.Knockdown of USP24 upregulated TBK1 K63-linked polyubiquitination,promoted the phosphorylation and nuclear translocation of IRF3,and in turn improved IFN-I production during EV71 infection.As a consequence,USP24 knockdown dramatically inhibited EV71 infection.This study revealed USP24 as a novel regulator of TBK1 activation,which promotes the understanding of immune evasion mechanisms of EV71 and could provide a potential strategy for treatment of EV71 infection.

关键词： Ubiquitin-specific protease 24(USP24) Enterovirus 71(EV71) TANK-binding kinase 1(TBK1) Type I interferons(IFN-I) Innate immunity

Role of Leptin in Immunity

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Cellular & Molecular Immunology 2007年第1期4卷 1-13页

作者： Queenie Lai Kwan Lam department of Pathology and Center of infection and Immunology The University of Hong Kong

Leptin, a protein hormone produced by the adipocytes, has long been recognized to regulate metabolism, neuroendorine and other physiological functions. Early findings of increased leptin production during infection and inflammation and dysregulated immune response in leptin signaling-deficient mice provide strong evidence for the involvement of leptin in the immune responses. Recent data have established the regulatory function for leptin in immunity similar to the function of a pro-inflammatory cytokine, while gene-targeting studies also demonstrated an essential role of leptin in regulating hematopoiesis and lymphopoiesis. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. This review discusses recent advances in understanding the role of leptin in immunity and leptin-signaling pathways involved in modulating immune homeostasis and autoimmune pathogenesis. Cellular ＆ Molecular Immunology. 2007;4（1）：1-13.

关键词： leptin leptin signaling pro-inflammatory cytokine immune response autoimmune disease