Role of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family in Herpes Simplex virus Type 1 (HSV-1) viral entry
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Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are the subgroup of the carcinoembryonic antigen family (CEA) which belongs to the immunoglobulin (Ig) superfamily. Herpes simplex virus type 1 (HSV-1) belongs to the subfamily of Alpha-herpesvirinae, which causes the overt infection by contacting with the secretions of an infected individual. Previous studies indicated the interaction between CEACAM proteins and HSV-1 via the siRNA depletion screen and the yeast two-hybrid (Y2H) system. The application of siRNA knockdown screen showed that CEACAM7 as a cellular protein required for viral replication, Y2H found the interaction between CEACAM family and glycoproteins. These results led to our hypothesis that CEACAM protein family may function as the viral entry receptor. In this project, we carried out several independent experiments in order to confirm the role of CEACAMs in HSV-1 viral entry. Transient overexpression of CEACAMs on HSV-1 viral-permissive cell lines (HeLa and 293T cells) led to a significant increase in viral replication. The interaction between CEACAM proteins and viral glycoproteins (gB, gD, gH) was confirmed by both Luminescence-based mammalian interactome mapping (LUMIER) assay and Co-immunoprecipitation assay. Finally, overexpression of CEACAM on viral non-permissive CHO cells identified the increase of HSV-1 early infection events when co-expressed with human receptors (HVEM or Nectin). Therefore, in this study, all the results suggested that CEACAM protein family may be a novel class of HSV-1 viral entry receptor.