SARS-CoV-2 productively infects primary human immune system cells in vitro and in CoviD-19 patients  

作　　者：Marjorie C.Pontelli italo A.Castro Ronaldo B.Martins Leonardo La Serra Flavio P.Veras Daniele C.Nascimento Camila M.Silva Ricardo S.Cardoso Roberta Rosales Rogério Gomes Thais M.Lima Juliano P.Souza Brenda C.Vitti Diego B.Caetite Mikhael H.F.de Lima Spencer D.Stumpf Cassandra E.Thompson Louis-Marie Bloyet Juliana E Toller-Kawahisa Marcela C.Giannini Leticia P.Bonjorno Marial.F.Lopes Sabrina S.Batah Li Siyuan Rodrigo Luppino-Assad Sergio C.L.Almeida Fabiola R.Oliveira Maira N.Benatti Lorena L.F.Pontes Rodrigo C.Santana Fernando C.Vilar Maria Auxiliadora-Martins Pei-Yong Shi Thiago M.Cunha Rodrigo T.Calado JoséC.Alves-Filho Dario S.Zamboni Alexandre T.Fabro Paulo Louzada-Junior Rene D.R.Oliveira Sean P.J.Whelan Fernando Q.Cunha Eurico Arruda 

机构地区：[1]Virology Research Center,Ribeirao Preto Medical School,University of Sao Paulo,ibeirao Preto,Sao Paulo 14049-900.Brazil [2]Center of Research in Inflammatory Diseases,Ribeirao Preto Medical School,University of Sao Paulo,Ribeirao Preto,Sao Paulo 14049-900,Brazil [3]Department of Celland Molecular Biology,Ribeirao Preto Medical School,Universityof Sao Paulo,Ribeirao Preto,Sao Paulo 14049-900 Brazil [4]Regional Blood Centerof Ribeirao Preto,Ribeirao Preto Medical Schol,University of Sao Paulo,Ribeirao Preto,Sao Paulo 14049-900,Brazil [5]Department of Biochemistry&Molecular Biology,the University of Texas Medical Branch,Galveston,TX7755,USA [6]Divisions of Clinical lmmunology,Infectious Diseases and Intensive Care Unit,Ribeirao Preto Medical Schoo,niversity of Sao Paulo,Ribeirao Preto,Sao Paulo 14049-900,Brazil [7]Department of Pathology,Ribeirao Preto Medical Schol,niversity of Sao Paulo,Ribeirao Preto,Sao Paulo 14049-900,Brazil [8]Department of Molecular Microbiology.Washington University in St.Louis,Saint Louis,MO 63110,USA

出　　处：《Journal of Molecular Cell Biology》2022年第4期51-64,共14页分子细胞生物学报（英文版）

基　　金：supported by Conselho Nacional de Desenvolviment Coientificoe Tecnologico(CNPq;310100/2017-8,403201/2020-9,and INCT 465539/2014-9);Fundagaode Amparoa Pesquisado Estado deSao Paulo(FAPESP;2013/16349-2 and 2014/02438-6);the National Institutes of Health(NIH;Al163019).M.C.P and R.G.were funded by CNPq(380849/2020-8).

摘　　要：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.

关 键 词：SARS-CoV-2 CoVID-19 LYMPHOCYTOPENIA peripheral blood mononuclear cell(PBMC) LYMPHOCYTES MONOCYTES apoptosis 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]