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-CoV-2-induced lymphopenia in COVID-19 patients.
【저자키워드】 immunology, Microbiology, 【초록키워드】 SARS-CoV-2, Apoptosis, Mitochondria, viral infection, ACE2, TMPRSS2, Lymphocytes, T cells, SARS-COV-2 infection, Infection, lung, in vitro, Antigen, RNA, Peripheral blood, lymphopenia, Protein, lymphocyte, T cell, Viral, Patient, target, SARS-CoV-2 RNA, Viral RNA, targets, receptors, T lymphocytes, receptor, Severe patient, cell death, patients, mechanism, COVID-19 patients, leukocytes, Infectious virus, Pathways, Viral antigen, Viral protein, severe patients, list, knockdown, viral particle, spike-ACE2, infect, Cell, SARS-CoV-2 viral, activated, demonstrated, experiments, expresse, peripheral blood cell, with COVID-19, 【제목키워드】 SARS-CoV-2, Infection, T lymphocyte,