Human herpesvirus 8 viral interleukin-6 signaling through gp130 promotes virus replication in primary effusion lymphoma and endothelial cells

The contributions of human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) to virus biology remain unclear. Here we examined the role of vIL-6/gp130 signaling in HHV-8 productive replication in primary effusion lymphoma and endothelial cells. Depletion and depletion-complementation experiments revealed that endoplasmic reticulum-localized vIL-6 activity via gp130 and gp130-activated signal transducer and activator of transcription (STAT) signaling, but not extracellular signal-regulated kinase (ERK) activation, was critical for vIL-6 proreplication activity. Our data significantly extend current understanding of vIL-6 function and associated mechanisms in HHV-8 biology.