Tetraspanin CD81 restricts Ebola virus infection and is antagonized by glycoprotein GP and matrix protein VP40.

Ebola virus GP reduces cell-surface availability of tetraspanins CD81, CD63, and CD9, and CD81 specifically restricts Ebola virus-like particle entry and viral replication.

• Why it matters: Viral entry and immune evasion depend on how Ebola virus reshapes host membranes and signaling, but the host factors that limit replication and infection remain incompletely defined.
• What they did: The study mapped GP effects on cell-surface proteins, tested filoviral versus non-filoviral glycoproteins, and assessed how CD81 loss or antibody clustering alters entry, replication, and NF-κB signaling induced by VP40 and trVLP.
• The result: CD81 suppresses Ebola virus-like particle entry and reduces Ebola virus RNA species, while GP and VP40 antagonize CD81 by lowering its total and surface expression, implying CD81 is a druggable inhibitory host factor.

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