THE JAPANESE FERAL MOUSE PIT1 AND PIT2 HOMOLOGS LACK AN ACIDIC RESIDUE AT POSITION-550 BUT STILL FUNCTION AS GIBBON APE LEUKEMIA-VIRUS RECEPTORS - IMPLICATIONS FOR VIRUS BINDING MOTIF

Murine cells are typically resistant to gibbon ape leukemia virus (GAL V). MMMol, a Japanese feral mouse cell line, is an exception in that t hese cells are susceptible to infection by GALV. We show here that MMM ol cells are further distinguished by their unusual receptor propertie s. MMMol cells infected by GALV are resistant to subsequent infection not only by GALV but also by amphotropic murine leukemia virus. This s uggests that GALV can enter MMMol via not only the GALV receptor (MolP it1) but also the amphotropic murine leukemia virus receptor (MolPit2) . Therefore, MolPit2 was cloned, sequenced, and compared with the prev iously reported sequence of MolPit1. Earlier studies have shown that a stretch of nine residues (position 550 to 558) in the fourth extracel lular domain of Pit1 is crucial for GALV entry acid that an acidic res idue at position 550 is indispensable. However, MolPit1 has isoleucine at this position and MolPit2 has glutamine at the corresponding posit ion (position 522), thus breaking this consensus. To determine what ef fect these specific changes in the fourth extracellular domain of MolP it1 and MolPit2 have on GALV receptor function, chimeric receptors wer e made by substituting the fourth extracellular domain of either MolPi t1 or MolPit2 for the same region of Pit2, a nonfunctional receptor fo r GALV. These chimeras were then tested in MDTF, a cell line that lack s functional GALV receptors and is resistant to GALV. Results show tha t MDTF expressing these chimeras became susceptible to GALV, whereas c ells expressing wild-type Pit2 remained resistant. Further, the MolPit 1 chimera was identical to Pit1 in efficiency, but the MolPit2 chimera proved substantially less efficient.