Membrane-Associated Kaposi Sarcoma-Associated Herpesvirus Glycoprotein B Promotes Cell Adhesion and Inhibits Migration of Cells via Upregulating IL-1β and TNF-α.

Hussein, Hosni A M; Abdel-Raouf, Usama M; Akula, Shaw M

OBJECTIVES Kaposi sarcoma-associated herpesvirus (KSHV) glycoprotein B (gB) is expressed on the viral envelope as well as on the cytoplasmic membrane of infected cells. In the current study, we aimed to decipher the impact of membrane-associated gB on adhesion and migration of cells via modulating the expression of cytokines. METHODS A combination of polymerase chain reaction array, cell adhesion assay, and wound-healing migration assay was conducted to study the influence of the gB-induced cytokines on cell adhesion and migration. RESULTS Membrane-associated gB was demonstrated to significantly upregulate the expression of IL-1β and TNF-α. Elevated levels of these cytokines were observed in conditioned medium (CM) collected from gB-expressing cells (gB-CM) compared to CM collected from untransfected cells or cells transfected with empty vector. KSHV gB-induced IL-1β and TNF-α play a role in the ability of gB-CM to mediate cell adhesion while inhibiting migration. CONCLUSION Our results provide novel evidence that demonstrates full-length gB expressed on cell membrane to mediate adhesion and inhibit migration of cells not only by autocrine mechanism mediated by RGD-based interactions [Hussein et al.: BMC Cancer 2016; 16: 148], but also by paracrine mechanism mediated by gB-induced IL-1β and TNF-α.