MUTATIONAL ANALYSIS OF THE PROPOSED GIBBON APE LEUKEMIA-VIRUS BINDING-SITE IN PIT1 SUGGESTS THAT OTHER REGIONS ARE IMPORTANT FOR INFECTION

Region A of Pit1 (residues 550 to 558 in domain IV) and related recept ors has remained the only sequence implicated in gibbon ape leukemia v irus (GALV) infection, and an acidic residue at the first position app eared indispensable, The region has also been proposed to be the GALV binding site, but this lacks empirical support. Whether an acidic resi due at the first position in this sequence is a definitive requirement for GALV infection has also remained unclear; certain receptors retai n function even in the absence of this acidic residue, We report here that in Pit1 an acidic residue is dispensable not only at position 550 but also at 553 alone and at both positions, Further, the virus requi res no specific residue at either position, Mutations generated a coll ection of region A sequences, often with fundamentally different physi cochemical properties (overall hydrophobicity or hydrophilicity and ne t charge of -1, or 0, or +1), and yet Pit1 remained an efficient GALV receptor. A comparison of these sequences and a few previously publish ed ones from highly efficient GALV receptors revealed that el en posit ion in region A can vary without affecting GALV entry. Even Pit2 is no nfunctional for GALV only because it has lysine at the first position in its region A, which is otherwise highly diverse from region A of Pi t1. We propose that region A itself is not the GALV binding motif and that Ether sequences are required for virus entry, Indeed, certain Pit 1/Pit2 chimeras revealed that sequences outside domain IV are specific ally important for GALV infection.