| Virus Name | Human herpesvirus 4 (Epstein-Barr virus) |
| Virus Short Name | EBV |
| Order | Herpesvirales |
| Virus Family | Herpesviridae |
| Virus Subfamily | Gammaherpesvirinae |
| Genus | Lymphocryptovirus |
| Species | Human herpesvirus 4 |
| Host | Human, mammals |
| Cell Tropism | B lymphocytes, oral epithelial cells, latency: remains latent in cd19+ b cells |
| Associated Disease | Mononucleosis, associated with environemental diseases: burkitt?s lymphoma nasopharyngeal carcinoma (npc) |
| Mode of Transmission | Contact, saliva |
| VIPR DB link | http://www.viprbrc.org/brc/vipr_allSpecies_search.do?method=SubmitForm&decorator=herpes |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/91/herpesviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Herpesviridae |
| Paper Title | Ephrin receptor A2 is a functional entry receptor for Epstein?Barr virus |
| Author's Name | Jia Chen, Karthik Sathiyamoorthy, Xianming Zhang, Samantha Schaller, Bethany E. Perez White, Theodore S. Jardetzky and Richard Longnecker |
| Journal Name | Nature Microbiology |
| Pubmed ID | 29292384 |
| Abstract | Epstein-Barr virus (EBV) is an oncogenic virus that infects more than 90% of the worlds population 1 . EBV predominantly infects human B cells and epithelial cells, which is initiated by fusion of the viral envelope with a host cellular membrane 2 . The mechanism of EBV entry into B cells has been well characterized 3 . However, the mechanism for epithelial cell entry remains elusive. Here, we show that the integrins alphavbeta5, alphavbeta6 and alphavbeta8 do not function as entry and fusion receptors for epithelial cells, whereas Ephrin receptor tyrosine kinase A2 (EphA2) functions well for both. EphA2 overexpression significantly increased EBV infection of HEK293 cells. Using a virus-free cell-cell fusion assay, we found that EphA2 dramatically promoted EBV but not herpes simplex virus (HSV) fusion with HEK293 cells. EphA2 silencing using small hairpin RNA (shRNA) or knockout by CRISPR-Cas9 blocked fusion with epithelial cells. This inhibitory effect was rescued by the expression of EphA2. Antibody against EphA2 blocked epithelial cell infection. Using label-free surface plasmon resonance binding studies, we confirmed that EphA2 but not EphA4 specifically bound to EBV gHgL and this interaction is through the EphA2 extracellular domain (ECD). The discovery of EphA2 as an EBV epithelial cell receptor has important implications for EBV pathogenesis and may uncover new potential targets that can be used for the development of novel intervention strategies. |
| Used Model | HEK293 cells |
| DOI | 10.1038/s41564-017-0081-7 |
