FUNGAL PHOSPHATE TRANSPORTER SERVES AS A RECEPTOR BACKBONE FOR GIBBONAPE LEUKEMIA-VIRUS

Pit1, the receptor for gibbon ape leukemia virus (GALV), is proposed t o be an integral membrane protein with five extracellular loops. Chime ras made between Pit1 homologs differing in permissivity for infection and between Pit1 and the related protein Pit2 have shown that the fou rth extracellular loop plays a critical role in infection. However, fu rther elucidation of the roles of the extracellular loops in infection is hampered by the high level of sequence similarity among these prot eins, The sodium-dependent phosphate transporter, Pho-4, from the fila mentous fungus Neurospora crassa is distantly related to Pit1 and -2, showing an amino acid identity of only 35% to Pit1 in the putative ext racellular loops. We show here that Pho-4 itself does not function as a receptor for GALV. Introduction of 12 Pit1-specific amino acid resid ues in the putative fourth extracellular loop of Pho-4 resulted in a f unctional GALV receptor. Therefore, the presence of a Pit1 loop 4-spec ific sequence is sufficient to confer receptor function for the mammal ian retrovirus GALV on the fungal phosphate transporter Pho-4.