The severe acute respiratory syndrome coronavirus 2(SARS-CovV-2)infection is associated with a hyperinflammatory state and lymphocytopenia,a hallmark that appears as both signature and prognosis of disease severity ou...The severe acute respiratory syndrome coronavirus 2(SARS-CovV-2)infection is associated with a hyperinflammatory state and lymphocytopenia,a hallmark that appears as both signature and prognosis of disease severity outcome.Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion,it is still unclear whether direct SARS-Cov-2 infection of immune cells could also play a role in this scenario by harboring viral replication.We found that monocytes,as well as both B and T lymphocytes,were susceptible to SARS-Cov-2 infection in vitro,accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell apoptosis.In addition,flow cytometry and immunofluorescence analysis revealed that SARS-Cov-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019(CoVID-19)patients.The rates of SARS-Cov-2-infected monocytes in peripheral blood mononuclear cells from CoVID-19 patients increased over time from symptom onset,with SARS-CoV-2-positive monocytes,B cells,and CD4+T lymphocytes also detected in postmortem lung tissue.These results indicated that SARS-CoV-2 infection of blood-circulating leukocytes in covID-19 patients might have important implications for disease pathogenesis and progression,immune dysfunction,and virus spread within the host.展开更多
The epithelial to mesenchymal transition(EMT)is a cellular program that drives de-differentiation of cells in both physiological and pathological processes.One of the characteristics of cells describing an EMT is the(...The epithelial to mesenchymal transition(EMT)is a cellular program that drives de-differentiation of cells in both physiological and pathological processes.One of the characteristics of cells describing an EMT is the(re)acquisition of a motility capacity that allows them to migrate through the original tissue as well as to other sites in the organism.The molecular mechanisms that control the EMT are rapidly emerging and here we add to the idea that the adaptation required for cells to commit to the EMT includes adjustments of the translation machinery and metabolic pathways to cope with a high demand of extracellular components.展开更多
基金supported by Conselho Nacional de Desenvolviment Coientificoe Tecnologico(CNPq310100/2017-8,403201/2020-9,and INCT 465539/2014-9)+3 种基金Fundagaode Amparoa Pesquisado Estado deSao Paulo(FAPESP2013/16349-2 and 2014/02438-6)the National Institutes of Health(NIHAl163019).M.C.P and R.G.were funded by CNPq(380849/2020-8).
文摘The severe acute respiratory syndrome coronavirus 2(SARS-CovV-2)infection is associated with a hyperinflammatory state and lymphocytopenia,a hallmark that appears as both signature and prognosis of disease severity outcome.Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion,it is still unclear whether direct SARS-Cov-2 infection of immune cells could also play a role in this scenario by harboring viral replication.We found that monocytes,as well as both B and T lymphocytes,were susceptible to SARS-Cov-2 infection in vitro,accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell apoptosis.In addition,flow cytometry and immunofluorescence analysis revealed that SARS-Cov-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019(CoVID-19)patients.The rates of SARS-Cov-2-infected monocytes in peripheral blood mononuclear cells from CoVID-19 patients increased over time from symptom onset,with SARS-CoV-2-positive monocytes,B cells,and CD4+T lymphocytes also detected in postmortem lung tissue.These results indicated that SARS-CoV-2 infection of blood-circulating leukocytes in covID-19 patients might have important implications for disease pathogenesis and progression,immune dysfunction,and virus spread within the host.
基金This work was partially supported by Fondo Clemente Estable(ANII)and PEDECIBA from Uruguay.T.Fernández-Calero received fellowships from CAP-Universidad de la República,ANII and the Embassy of France in Uruguay.M.Davyt received a fellowship from CSIC-Universidad de la República.
文摘The epithelial to mesenchymal transition(EMT)is a cellular program that drives de-differentiation of cells in both physiological and pathological processes.One of the characteristics of cells describing an EMT is the(re)acquisition of a motility capacity that allows them to migrate through the original tissue as well as to other sites in the organism.The molecular mechanisms that control the EMT are rapidly emerging and here we add to the idea that the adaptation required for cells to commit to the EMT includes adjustments of the translation machinery and metabolic pathways to cope with a high demand of extracellular components.
