A carboxy-terminal mutant spleen focus-forming virus (SFFV) envelope glycoprotein is transport-competent, but non-leukemogenic.
The Friend spleen focus-forming virus (F-SFFV) codes for a transport-defective leukemogenic envelope glycoprotein designated as gp52. We have previously shown that the external domain of gp52 carries the determinants responsible for its transport defect. Consistent with this idea, truncated gp52 molecules that lack a hydrophobic membrane anchor were transport-defective, and were not secreted from cells. In this report, we describe the construction of a mutant SFFV envelope gene that codes for altered gp52 molecules in which the carboxyl-terminal hydrophobic residues are replaced with exogenous hydrophilic residues encoded by the vector-derived sequences. The mutant env gene was expressed using the retroviral expression vector, pLXSN, and the mutant envelope protein was found to be transport-competent, and efficiently secreted from the cells. However, M-MuLV pseudotypes of the retroviral vectors expressing the mutant genome were found to be non-leukemogenic in mice.
Srinivas
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RV
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38101.
Rui
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Compans
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D015752:Genes, env; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000382:microbiology*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D008979:Moloney murine leukemia virus / Q000235:genetics; D009154:Mutation; D013155:Spleen Focus-Forming Viruses / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D014759:Viral Envelope Proteins; C077794:gp52 protein, spleen focus-forming virus