Fig 9.

Summary of our main findings and conclusions. Previous studies revealed that vIL-6 is expressed in latently infected PEL cells and functions in the ER compartment to promote cell growth and survival (5). The present study identified VKORC1v2 as an ER-localized binding partner of vIL-6 and mapped the vIL-6-binding region of VKORC1v2 to residues 31 to 39 (vBD), which is capable, when fused to a heterologous protein and targeted to the ER, of interfering with vIL-6 binding to VKORC1v2 and suppressing PEL growth and survival. These outcomes were also seen upon VKORC1v2 depletion and could be rescued by (shRNA-refractory) wild-type VKORC1v2 but not by a dialanine variant (DY₃₉AA) with diminished ability to bind vIL-6. Neither VKORC1v2 depletion nor vBD overexpression had detectable negative effects on gp130 signaling, and VKORC1v2 overexpression did not enhance it. These findings suggest that activities of vIL-6 connected with its binding to VKORC1v2 are mediated independently of g130 signaling, which is known to promote growth and survival of various cell types. However, the mechanism of vIL-6 activity via VKORC1v2 association remains to be determined.