A 13-amino-acid Pit1-specific loop 4 sequence confers feline leukemia virus subgroup B receptor function upon Pit2

Abstract

Feline leukemia virus subgroup B (FeLV-B) and gibbon ape leukemia virus (GALV) utilize the human protein Pit1 but not the related protein, Pit2, as receptor. A stretch of 9 amino acids, named region A, was identified in the putative fourth extracellular loop of Pit1 (residues 550 through 558) as critical for FeLV-B and GALV receptor function. However, the presence of Pit1 region A did not confer receptor function for FeLV-B upon Pit2, while it did so for GALV. We have here shown that the presence of two Pit1-specific loop 4 residues (tyrosine 546 and valine 548) in addition to Pit1 region A is sufficient to make Pit2 an efficient FeLV-B receptor; that is, a stretch of 13 amino acids encompassing all loop 4 amino acid differences between Pit1 and Pit2 comprises a C-terminal determinant for FeLV-B receptor function. Thus, the same limited receptor region is sufficient to confer receptor function for both viruses upon Pit2.

FIG. 1

Alignment of putative extracellular loop sequences for Pit1, Pit2, RatPit2, and MusPit1. Numbers at the left of the sequences correspond to the positions of the first and last amino acids shown. Dots indicate amino acid identity to Pit1. Gaps introduced for alignment are indicated by dashes. The sequences underlined are region A and the loop 2 sequence mutated in the chimeras A1, A2, and A3. All residues mutated in this study are in boldface.