ACE2-independent infection of T lymphocytes by SARS-CoV-2

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• SARS-CoV-2 causes lymphopenia in severe COVID-19.
• The role of lymphocytes as SARS-CoV-2 targets remains unclear.
• Viral RNA/antigen detection in T cells suggests potential infection.

Purpose of the Study:

• To confirm SARS-CoV-2 infects T lymphocytes.
• To elucidate the mechanism of SARS-CoV-2 entry into T cells.
• To understand the pathways leading to T cell death in COVID-19.

Main Methods:

• Detection of SARS-CoV-2 antigen and infectious virus in patient peripheral blood cells (PBCs) and lung T cells.
• In vitro infection of T lymphocytes, including activated CD4+ T cells.
• Experiments using ACE2 knockdown and receptor blocking to assess infection pathways.
• Analysis of T cell apoptosis and cell death pathways (ROS-HIF-1a).
• Investigation of LFA-1 as a potential viral entry molecule.

Main Results:

• SARS-CoV-2 antigen and infectious virus confirmed in T cells from patients.
• In vitro studies demonstrated SARS-CoV-2 infects T lymphocytes, particularly activated CD4+ T cells.
• Viral entry was independent of the spike-ACE2/TMPRSS2 pathway.
• T cells positive for viral antigen exhibited increased apoptosis.
• Mitochondria, ROS, and HIF-1a pathways were implicated in SARS-CoV-2-induced T cell death.
• LFA-1 was identified as the likely entry molecule for SARS-CoV-2 into T cells.

Conclusions:

• This study confirms SARS-CoV-2 infects T cells, including activated CD4+ T cells.
• The infection occurs via a spike-ACE2-independent mechanism, likely mediated by LFA-1.
• SARS-CoV-2 infection induces T cell apoptosis through ROS-HIF-1a dependent pathways.
• These findings provide insights into the mechanisms underlying SARS-CoV-2-induced lymphopenia in COVID-19.