The differential targeting of BST2 isoforms by Vpu from pandemic HIV-1 group M might therefore indicate that overcoming the human BST2 NFκB signaling capacity (long isoform) while still maintaining a pool of BST2 at the cell surface (short isoform) represented a critical adaptation required for the efficient zoonotic transmission that led to the HIV/AIDS pandemic. This evidence concerns the gene BST2 and AIDS.