%0 Journal Article %1 SmithJVI.00428-20 %A Smith, Nicholas A. %A Coleman, Carrie B. %A Gewurz, Benjamin E. %A Rochford, Rosemary %D 2020 %I American Society for Microbiology Journals %J Journal of Virology %K T-cell epstein-barr myown %R 10.1128/JVI.00428-20 %T CD21 (Complement Receptor 2) is the receptor for Epstein-Barr virus entry into T cells %U https://jvi.asm.org/content/early/2020/03/27/JVI.00428-20 %X Epstein-Barr virus (EBV) is associated with a number of T-cell diseases including some peripheral T-cell lymphomas, hemophagocytic lymphohistiocytosis, and chronic active EBV. The tropism of EBV for B-cells and epithelial cell infection has been well characterized but infection of T-cells has been minimally explored. We have recently shown that the EBV type 2 (EBV-2) strain has the unique ability to infect mature T-cells. Utilizing an ex vivo infection model, we sought to understand the viral glycoprotein and cellular receptor required for EBV-2 infection of T-cells. Here we show using a neutralizing antibody assay that the viral gp350 and the complement receptor 2, CD21 are required for CD3+ T-cell infection. Using the HB5 anti-CD21 antibody clone but not the Bly-4 anti-CD21 antibody clone, we detected expression of CD21 on both CD4+ and CD8+ T-cells with the highest expression on naive CD4 and CD8+ T-cell subsets. Using CRISPR to knockout CD21, we demonstrated that CD21 is necessary for EBV entry into the Jurkat T-cell line. Together, these results indicate that EBV uses the same viral glycoprotein and cellular receptor for both T and B-cell infection.Importance Epstein-Barr virus (EBV) has a well-described tropism for B-cells and epithelial cells. More recently, we described the ability of a second strain of EBV, EBV Type 2, to infect mature peripheral T-cells. Using a neutralizing antibody assay, we identified that EBV used the viral glycoprotein, gp350, and the cellular CD21 to gain entry into mature peripheral T-cells. CRISPR-Cas9 deletion of CD21 on the Jurkat T-cell line confirmed that CD21 is required for EBV infection. This study has broad implications as we have defined a function for CD21 on mature peripheral T-cells, e.g. as a receptor for EBV. In addition, the requirement for gp350 for T-cell entry has implications for EBV vaccine studies currently targeting the gp350 glycoprotein to prevent EBV associated diseases.

@article{SmithJVI.00428-20, abstract = {Epstein-Barr virus (EBV) is associated with a number of T-cell diseases including some peripheral T-cell lymphomas, hemophagocytic lymphohistiocytosis, and chronic active EBV. The tropism of EBV for B-cells and epithelial cell infection has been well characterized but infection of T-cells has been minimally explored. We have recently shown that the EBV type 2 (EBV-2) strain has the unique ability to infect mature T-cells. Utilizing an ex vivo infection model, we sought to understand the viral glycoprotein and cellular receptor required for EBV-2 infection of T-cells. Here we show using a neutralizing antibody assay that the viral gp350 and the complement receptor 2, CD21 are required for CD3+ T-cell infection. Using the HB5 anti-CD21 antibody clone but not the Bly-4 anti-CD21 antibody clone, we detected expression of CD21 on both CD4+ and CD8+ T-cells with the highest expression on naive CD4 and CD8+ T-cell subsets. Using CRISPR to knockout CD21, we demonstrated that CD21 is necessary for EBV entry into the Jurkat T-cell line. Together, these results indicate that EBV uses the same viral glycoprotein and cellular receptor for both T and B-cell infection.Importance Epstein-Barr virus (EBV) has a well-described tropism for B-cells and epithelial cells. More recently, we described the ability of a second strain of EBV, EBV Type 2, to infect mature peripheral T-cells. Using a neutralizing antibody assay, we identified that EBV used the viral glycoprotein, gp350, and the cellular CD21 to gain entry into mature peripheral T-cells. CRISPR-Cas9 deletion of CD21 on the Jurkat T-cell line confirmed that CD21 is required for EBV infection. This study has broad implications as we have defined a function for CD21 on mature peripheral T-cells, e.g. as a receptor for EBV. In addition, the requirement for gp350 for T-cell entry has implications for EBV vaccine studies currently targeting the gp350 glycoprotein to prevent EBV associated diseases.}, added-at = {2020-04-24T04:22:34.000+0200}, author = {Smith, Nicholas A. and Coleman, Carrie B. and Gewurz, Benjamin E. and Rochford, Rosemary}, biburl = {https://www.bibsonomy.org/bibtex/26f0c2a4b523576f9519781312aefafeb/bgewurz}, doi = {10.1128/JVI.00428-20}, elocation-id = {JVI.00428-20}, eprint = {https://jvi.asm.org/content/early/2020/03/27/JVI.00428-20.full.pdf}, interhash = {b813a55e51d7b01f51b362fb191a2c35}, intrahash = {6f0c2a4b523576f9519781312aefafeb}, issn = {0022-538X}, journal = {Journal of Virology}, keywords = {T-cell epstein-barr myown}, publisher = {American Society for Microbiology Journals}, timestamp = {2020-04-28T23:54:56.000+0200}, title = {CD21 (Complement Receptor 2) is the receptor for Epstein-Barr virus entry into T cells}, url = {https://jvi.asm.org/content/early/2020/03/27/JVI.00428-20}, year = 2020 }