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
Dear Editor,Swine acute diarrhoea syndrome coronavirus (SADS-Co V)is a novel swine enteric coronavirus belonged to the Coronaviridae family,Alphacoronavirus genus (Zhou P et al.2018).The clinical signs of SADS include...Dear Editor,Swine acute diarrhoea syndrome coronavirus (SADS-Co V)is a novel swine enteric coronavirus belonged to the Coronaviridae family,Alphacoronavirus genus (Zhou P et al.2018).The clinical signs of SADS include acute diarrhoea and vomiting,which was similar with the infection of porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCo V)(Wang et al.2019).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.
基金supported by National Natural Science Foundation of China (31830096)。
文摘Dear Editor,Swine acute diarrhoea syndrome coronavirus (SADS-Co V)is a novel swine enteric coronavirus belonged to the Coronaviridae family,Alphacoronavirus genus (Zhou P et al.2018).The clinical signs of SADS include acute diarrhoea and vomiting,which was similar with the infection of porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCo V)(Wang et al.2019).