Potential entry receptors for human γ-herpesvirus into epithelial cells: A plausible therapeutic target for viral infections

Abstract

Herpesviruses are ubiquitous viruses, specifically the Epstein Barr virus (EBV). EBV and Kaposi's sarcoma-associated herpesvirus (KSHV) establish their latency for a long period in B-cells and their reactivation instigates dreadful diseases from cancer to neurological modalities. The envelope glycoprotein of these viruses makes an attachment with several host receptors. For instance; glycoprotein 350/220, gp42, gHgL and gB of EBV establish an attachment with CD21, HLA-DR, Ephs, and other receptor molecules to hijack the B- and epithelial cell machinery. Ephs are reported recently as potent receptors for EBV entry into epithelial cells. Eph receptors play a role in the maintenance and control of various cellular processes including morphology, adhesion, proliferation, survival and differentiation. Alterations in the structure and expression of Eph and ephrin (Eph ligands) molecules is entangled with various pathologies including tumours and neurological complications. Along with Eph, integrins, NRP, NMHC are also key players in viral infections as they are possibly involved in viral transmission, replication and persistence. Contrarily, KSHV gH is known to interact with EphA2 and -A4 molecules, whereas in the case of EBV only EphA2 receptors are being reported to date. The ELEFN region of KSHV gH was involved in the interaction with EphA2, however, the interacting region of EBV gH is elusive. Further, the gHgL of KSHV and EBV form a complex with the EphA2 ligand-binding domain (LBD). Primarily by using gL both KSHV and EBV gHgL bind to the peripheral regions of LBD. In addition to γ-herpesviruses, several other viruses like Nipah virus, Cedar virus, Hepatitis C virus and Rhesus macaque rhadinovirus (RRV) also access the host cells via Eph receptors. Therefore, we summarise the possible roles of Eph and ephrins in virus-mediated infection and these molecules could serve as potential therapeutic targets.

TRIM26 restricts Epstein–Barr virus infection in nasopharyngeal epithelial cells through K48‐linked ubiquitination of HSP‐90β

“…EBV treatment induced HSP-90β expression in a time-dependent manner, and HSP-90 inhibitors, 17-AAG and GA, decreased the levels of the host receptor EphA2 in a dose-dependent manner. EphA2 has been identified as a host receptor or co-factors for several viruses, including EBV, 10,11 KSHV, 27 and hepatitis C virus. 28 It has also been reported that HSP-90 inhibitors, such as 17-DMAG, 17-AAG, or Ganetespib could kill Epstein-Barr virus (EBV)-infected cells by reducing the level of EBV EBNA-1 and/or LMP1, which Lysates from HEK293T cells transiently cotransfected with HA-Ub, TRIM26-Flag, and Myc-HSP-90AB1 were subjected to immunoprecipitation with Myc antibody followed by immunoblot analysis.…”

Progress in Prophylactic and Therapeutic EBV Vaccine Development Based on Molecular Characteristics of EBV Target Antigens

“…Gp350 is a highly glycosylated protein that is 901 amino acids long, with half of its mass being carbohydrate. Gp350 makes an initial connection to B lymphocytes by binding to their complement receptor type 2 (CR2) or CD21, respectively [15]. CR2 is a transmembrane protein found on B lymphocytes, T lymphocytes, and follicular dendritic cells; moreover, it plays a role in the development of humoral immunity response [16].…”

Development of Epstein-Barr virus-associated gastric cancer: Infection, inflammation, and oncogenesis

“…EBV infects B lymphocytes through the binding of the viral glycoprotein gp350 to the high-affinity receptor CD21, followed by binding of gp42 to HLA class II molecules, resulting in membrane fusion[ 17 ]. In contrast, when low-affinity co-receptors are used to infect CD21-negative epithelial cells, the infection efficiency is extremely low (Figure 1 ).…”