SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19.However,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cel...SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19.However,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cells from patients.Here,we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells(PBCs)or postmortem lung T cells,and the infectious virus could also be detected from viral antigen-positive PBCs.We next prove that SARS-CoV-2 infects T lymphocytes,preferably activated CD4+T cells in vitro.Upon infection,viral RNA,subgenomic RNA,viral protein or viral particle can be detected in the T cells.Furthermore,we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments.Next,we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis.In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways.Finally,we demonstrated that LFA-1,the protein exclusively expresses in multiple leukocytes,is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells,compared to a list of other known receptors.Collectively,this work confirmed a SARS-CoV-2 infection of T cells,in a spike-ACE2-independent manner,which shed novel insights into the underlying mechanisms of SARS-CoV2-induced lymphopenia in COVID-19 patients.展开更多
基金the Natural Science Foundation of China(excellent scholars 81822028,82041013,and 81772199 to P.Z.,and 81974456 and 82170081 to H.L.Z.)Strategic Priority Research Program of the CAS(grant number XDB29010204)to P.Z.
文摘SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19.However,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cells from patients.Here,we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells(PBCs)or postmortem lung T cells,and the infectious virus could also be detected from viral antigen-positive PBCs.We next prove that SARS-CoV-2 infects T lymphocytes,preferably activated CD4+T cells in vitro.Upon infection,viral RNA,subgenomic RNA,viral protein or viral particle can be detected in the T cells.Furthermore,we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments.Next,we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis.In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways.Finally,we demonstrated that LFA-1,the protein exclusively expresses in multiple leukocytes,is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells,compared to a list of other known receptors.Collectively,this work confirmed a SARS-CoV-2 infection of T cells,in a spike-ACE2-independent manner,which shed novel insights into the underlying mechanisms of SARS-CoV2-induced lymphopenia in COVID-19 patients.
