CD21 (Complement Receptor 2) Is the Receptor for Epstein-Barr Virus Entry into T Cells

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Epstein-Barr virus (EBV) primarily infects B cells and epithelial cells.
• EBV is linked to T-cell diseases, but T-cell tropism is poorly understood.
• EBV type 2 (EBV-2) has recently been shown to infect mature T cells.

Purpose of the Study:

• To investigate the viral and cellular factors enabling EBV-2 infection of T cells.
• To identify the specific viral glycoprotein and cellular receptor involved in EBV-2 T-cell entry.
• To understand the implications for EBV pathogenesis and vaccine development.

Main Methods:

• Utilized an ex vivo infection model for mature T cells.
• Employed neutralizing-antibody assays to identify viral and cellular targets.
• Used CRISPR-Cas9 gene editing to knock out CD21 in Jurkat T-cells.
• Detected CD21 expression on T-cell subsets via flow cytometry.

Main Results:

• Viral glycoprotein gp350 and cellular receptor CD21 are essential for EBV-2 infection of CD3+ T cells.
• CD21 is expressed on CD4+ and CD8+ T cells, particularly naive subsets.
• CRISPR-mediated CD21 knockout abrogated EBV entry into Jurkat T-cells.
• EBV utilizes the same entry mechanism for both T and B cells.

Conclusions:

• EBV-2 employs gp350 and CD21 for T-cell entry, mirroring B-cell tropism.
• This study defines CD21 as a functional receptor for EBV on mature T cells.
• The findings have implications for EBV-associated T-cell diseases and gp350-targeted vaccine strategies.