LEUKEMOGENIC RETROVIRAL GLYCOPROTEIN--GP55-GP70S

In friend erythroleukemia, the env membrane glycoprotein (gp55) encoded
by spleen focus-forming (SFFV) virus binds to erythropoietin receptors
(EpoR) to stimulate erythroblastosis. Indeed, a family of murine env
glycoproteins (gp70s of MCF viruses) that are related to gp55 seems to
be an inherited repository of promiscuous hemopoietin agonists.
Recently, we obtained evidence that mice homozygous for Fv-2r are
resistant to erythroleukemia due to down-modulation of their EpoR
response pathway. We propose: (1) Use cell culture assays, antisera, and
mutants that we have available to thoroughly analyze the mechanism of
gp55-EpoR interaction. (2) Use Fv-2r and other Friend virus resistance
genes to study mechanisms whereby host genetic variation controls
susceptibility to an oncogenic protein. (3) Analyze MCF gp70s as
hemopoietin agonists an as mediators of virus infection. (4) Continue to
analyze the mechanism whereby SFFV proviral integration immortalizes
erythroblasts. (5) A CDNA encoding cell surface receptors (ecoR) for
ecotropic host-range murine retroviruses has been molecularly cloned. In
agreement with data for HIV, we found that infection requires a host
accessory factor in addition to the virus-binding receptor protein.
Identify and study this accessory factor. Also, we found that expression
of ecoR in Xenopus oocytes increases facilitated transport of basic
amino acids. Analyze this normal function of ecoR and its perturbation
by infection. Study the metabolism and processing of ecoR and the
mechanism of interference to superinfection. This program concerns
pathogenic interactions of retroviral env glycoproteins with host cell
receptors, a field that has become central for understanding naturally
occurring human and animal retroviral diseases. The murine model has
unique experimental advantages.