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J. Virol., Oct 1996, 6982-6986, Vol 70, No. 10
RD Schneiderman, KB Farrell, CA Wilson and MV Eiden
Murine cells are typically resistant to gibbon ape leukemia virus (GALV).
MMMol, a Japanese feral mouse cell line, is an exception in that these
cells are susceptible to infection by GALV. We show here that MMMol cells
are further distinguished by their unusual receptor properties. MMMol cells
infected by GALV are resistant to subsequent infection not only by GALV but
also by amphotropic murine leukemia virus. This suggests that GALV can
enter MMMol via not only the GALV receptor (MolPit1) but also the
amphotropic murine leukemia virus receptor (MolPit2). Therefore, MolPit2
was cloned, sequenced, and compared with the previously reported sequence
of MolPit1. Earlier studies have shown that a stretch of nine residues
(position 550 to 558) in the fourth extracellular domain of Pit1 is crucial
for GALV entry and that an acidic residue at position 550 is indispensable.
However, MolPit1 has isoleucine at this position and MolPit2 has glutamine
at the corresponding position (position 522), thus breaking this consensus.
To determine what effect these specific changes in the fourth extracellular
domain of MolPit1 and MolPit2 have on GALV receptor function, chimeric
receptors were made by substituting the fourth extracellular domain of
either MolPit1 or MolPit2 for the same region of Pit2, a nonfunctional
receptor for GALV. These chimeras were then tested in MDTF, a cell line
that lacks functional GALV receptors and is resistant to GALV. Results show
that MDTF expressing these chimeras became susceptible to GALV, whereas
cells expressing wild-type Pit2 remained resistant. Further, the MolPit1
chimera was identical to Pit1 in efficiency, but the MolPit2 chimera proved
substantially less efficient.
Copyright © 1996, American Society for Microbiology
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
Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland 20892-4068, USA.
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