Mutations in the env gene of friend spleen focus-forming virus overcome Fv-2r-mediated resistance to Friend virus-induced erythroleukemia.
Although Fv-2r homozygous mice are resistant to leukemias induced either by an erythropoietin-encoding virus or by wild-type Friend virus (FV) (M. E. Hoatlin, S. L. Kozak, F. Lilly, A. Chakraborti, C. A. Kozak, and D. Kabat, Proc. Natl. Acad. Sci. USA 87:9985-9989, 1990), they are susceptible to some variants of FV (R. A. Steeves, E. A. Mirand, A. Bulba, and P. J. Trudel, Int. J. Cancer 5:349-356, 1970; R. W. Geib, M. B. Seaward, M. L. Stevens, C.-L. Cho, and M. Majumdar, Virus Res. 14:161-174, 1989). To localize the virus gene involved in influencing the host range, we cloned and sequenced the env gene of the BB6 variant of FV (Steeves et al., Int. J. Cancer 5:349-356, 1970). In comparison with the wild-type env gene, the BB6 variant contains a 159-bp deletion that eliminates the membrane-proximal portion of the extracellular domain and 58 point mutations resulting in 13 amino acid changes. Substitution of the variant env gene for the wild-type env gene resulted in a recombinant virus that produced a Friend virus-like disease in Fv-2r homozygotes. Our results identify the spleen focus-forming virus env gene as the viral gene involved in this virus-host interaction. Additionally, they suggest that the product of the Fv-2r gene modifies the interaction between the spleen focus-forming virus envelope protein and the erythropoietin receptor.
Majumdar
M K
MK
Department of Life Sciences, Indiana State University, Terre Haute.
Cho
C L
CL
Fox
M T
MT
Eckner
K L
KL
Kozak
S
S
Kabat
D
D
Geib
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D005622:Friend murine leukemia virus / Q000235:genetics* / Q000472:pathogenicity; D005784:Gene Amplification; D015752:Genes, env / Q000235:genetics*; D006790:Host-Parasite Interactions / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics*; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics* / Q000473:pathology; D007942:Leukemia, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009154:Mutation; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000382:microbiology; D013155:Spleen Focus-Forming Viruses / Q000235:genetics / Q000472:pathogenicity; D014775:Virus Activation