CD81 (TAPA-1) belongs to the transmembrane 4 superfamily (tetraspanin family). CD81 is a widely expressed cell-surface protein that is characterized by the presence of four transmembranic domains, short N and C termini, a small extracellular loop (SEL) and a large extra-cellular loop (LEL) (1). It is expressed on cells of hematopoietic, neuroectodermal and mesenchymal origin and plays a role in the regulation of cell development, cell-growth and signal transduction. CD81 plays a critical role in Hepatitis C Infection and is involved in HCV entry due to its ability to interact with virus‘ E1/E2 glycoproteins (2,3). CD81 is an essential HCV host factor as silencing of CD81 expression by CD81-specific monoclonal antibodies in hepatoma cells inhibits HCV entry (4).