The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality.However,the molecular characteristics and pathological features underlying COVID-...The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality.However,the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown.To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach,fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia.After virus inactivation,a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues.We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism,blood coagulation,immune response,angiogenesis,and cell microenvironment regulation.Several inflammatory factors were upregulated,which was possibly caused by the activation of NF-κB signaling.Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered.Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection,and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.展开更多
HIV-1-specific cytotoxic T lymphocytes(CTLs) and neutralizing antibodies(NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Her...HIV-1-specific cytotoxic T lymphocytes(CTLs) and neutralizing antibodies(NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4+ T cells,primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures. However, the same neutralizing antibody was able to contain viruses by antibody-dependent cell-mediated virus inhibition in vitro,which was mediated by natural killer cells(NKs) and dependent on an Fc-Fc receptor interaction.Meanwhile, bulk CTLs from HIV-1 controllers were more effective in suppression of virus replication than those from progressors. These findings indicate that control of HIV-1 replication in activated CD4^+ T cells is ineffectively mediated by neutralizing antibodies alone, but that both CTLs and antibody-dependent NK-mediated immune mechanisms contribute to viral containment. Our study systemically compared three major players in controlling HIV-1 infection, CTLs, NAbs, and NKs, in an autologous system and highlighted the multifactorial mechanisms for viral containment and vaccine success.展开更多
Dear Editor,The early diagnosis and prognosis of COVID-19 remain major challenges.At present,there are few studies focusing on the changes of sera proteome betAA/een active and recovered COVID-19 patients,and almost n...Dear Editor,The early diagnosis and prognosis of COVID-19 remain major challenges.At present,there are few studies focusing on the changes of sera proteome betAA/een active and recovered COVID-19 patients,and almost no biomarkers in sera are used to predict the function disorder of the injured tissues and organs in COVID-19 patients.In this study,we applied sera proteomics in the active and recovered COVID-19 patients,as well as healthy volunteers,combining with pathological staining of the patients'tissues to identify the potential prognosis biomarkers that can reflect specific organ damage.展开更多
基金supported by the National Science and Technology Major Projects(2018ZX09711003).
文摘The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality.However,the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown.To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach,fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia.After virus inactivation,a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues.We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism,blood coagulation,immune response,angiogenesis,and cell microenvironment regulation.Several inflammatory factors were upregulated,which was possibly caused by the activation of NF-κB signaling.Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered.Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection,and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.
基金supported by the Fund for Jiangsu Specially-Appointed Professor(2014JSTPJS-53)the Innovation Fund from National Center for AIDS/STD Control and Prevention,China CDC,Capital Medical University Key Laboratory Project(2-03-02-BJYAH 2016006)China’s 12th Five-Year Major Project on the Prevention and Treatment of AIDS
文摘HIV-1-specific cytotoxic T lymphocytes(CTLs) and neutralizing antibodies(NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4+ T cells,primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures. However, the same neutralizing antibody was able to contain viruses by antibody-dependent cell-mediated virus inhibition in vitro,which was mediated by natural killer cells(NKs) and dependent on an Fc-Fc receptor interaction.Meanwhile, bulk CTLs from HIV-1 controllers were more effective in suppression of virus replication than those from progressors. These findings indicate that control of HIV-1 replication in activated CD4^+ T cells is ineffectively mediated by neutralizing antibodies alone, but that both CTLs and antibody-dependent NK-mediated immune mechanisms contribute to viral containment. Our study systemically compared three major players in controlling HIV-1 infection, CTLs, NAbs, and NKs, in an autologous system and highlighted the multifactorial mechanisms for viral containment and vaccine success.
基金This work was supported by the National Science and Technology Major Project(2018ZX09711003)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2020-I2M-CoV19-001).
文摘Dear Editor,The early diagnosis and prognosis of COVID-19 remain major challenges.At present,there are few studies focusing on the changes of sera proteome betAA/een active and recovered COVID-19 patients,and almost no biomarkers in sera are used to predict the function disorder of the injured tissues and organs in COVID-19 patients.In this study,we applied sera proteomics in the active and recovered COVID-19 patients,as well as healthy volunteers,combining with pathological staining of the patients'tissues to identify the potential prognosis biomarkers that can reflect specific organ damage.