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Journal of Virology, January 2000, p. 237-244, Vol. 74, No. 1
Department of Biochemistry and Molecular
Biology, Oregon Health Sciences University, Portland, Oregon 97201-3098
Received 17 June 1999/Accepted 22 September 1999
Because mutations in envelope glycoproteins of retroviruses or in
their cell surface receptors can eliminate function by multiple mechanisms, it has been difficult to unambiguously identify sites for
their interactions by site-directed mutagenesis. Recently, we developed
a gain-of-function approach to overcome this problem. Our strategy
relies on the fact that feline leukemia virus subgroup B (FeLV-B) and
amphotropic murine leukemia virus (A-MLV) have closely related gp70
surface envelope glycoproteins and use related Na+-dependent phosphate symporters, Pit1 and Pit2,
respectively, as their receptors. We previously observed that
FeLV-B/A-MLV envelope glycoprotein chimeras spliced between the
variable regions VRA and VRB were unable to use Pit1 or Pit2 as a
receptor but could efficiently use specific Pit1/Pit2 chimeras. The
latter study suggested that the VRA of A-MLV and FeLV-B functionally
interact with the presumptive extracellular loops 4 and 5 (ECL4 and -5) of their respective receptors, whereas VRB interacts with ECL2. We also
found that FeLV-B gp70 residues F60 and P61 and A-MLV residues Y60 and
V61 in the first disulfide-bonded loop of VRA were important for
functional interaction with the receptor's ECL4 or -5. We have now
extended this approach to identify additional VRA and VRB residues that
are involved in receptor recognition. Our studies imply that FeLV-B VRA
residues F60 and P61 interact with the Pit1 ECL5 region, whereas VRA
residues 66 to 78 interact with Pit1 ECL4. Correspondingly, A-MLV VRA
residues Y60 and V61 interact with the Pit2 ECL5 region, whereas
residues 66 to 78 interact with Pit2 ECL4. Similar studies that focused
on the gp70 VRB implicated residues 129 to 139 as contributing to
specific interactions with the receptor ECL2. These results identify
three regions of gp70 that interact in a specific manner with distinct portions of their receptors, thereby providing a map of the
functionally interacting surfaces.
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
A Comprehensive Approach to Mapping the Interacting
Surfaces of Murine Amphotropic and Feline Subgroup B Leukemia Viruses
with Their Cell Surface Receptors
*
Corresponding author. Mailing address: Department of
Biochemistry and Molecular Biology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Mail Code L224, Portland, OR 97201-3098. Phone: (503) 494-2548. Fax: (503) 494-8393. E-mail:
tailorc{at}ohsu.edu.
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