Tetraspanin CD9 Is a Positive Regulator of Filovirus Egress

Filoviruses, including Ebola (EBOV) and Marburg (MARV) viruses, are zoonotic pathogens that cause severe hemorrhagic fever in humans, with mortality rates reaching up to 90%. Filovirus egress and spread are driven by the viral matrix protein VP40 and regulated both positively and negatively by a growing number of specific host interactors. Here, we identify tetraspanin protein CD9, a plasma membrane organizing and scaffolding protein, as playing a role in facilitating efficient egress of EBOV and MARV. Indeed, we observed a significant decrease in viral egress of VLPs and live filoviruses from CD9-KD cells as compared to that from WT cells. Moreover, exogenous expression of CD9 rescued egress of VP40 VLPs close to WT levels in the CD9-KD cells. These findings identify tetraspanin CD9 as a positive regulator of filovirus egress, and thus CD9 may represent a potential new target for antiviral therapies targeting the late stage of the filovirus lifecycle.