A 585-bp deletion found in the spleen focus-forming virus (SFFV) env gene is responsible for the defective intracellular transport of SFFV gp52.
The Friend spleen focus-forming virus (F-SFFV) codes for a transport defective, leukemogenic envelope glycoprotein designated as gp52. Gp52 closely resembles the envelope glycoproteins (gp70-p15E) encoded by the mink cell focus-forming viruses (MCFV). The major differences between SFFV and MCFV include a 585-bp deletion and a frame-shift mutation near the 3' end of the SFFV env gene. We have constructed a mutant MCFV env gene, which contains a 585-bp deletion like that found in the SFFV env gene, and expressed this gene using recombinant vaccinia vectors or retroviral vectors. The mutant MCFV env gene expressed a truncated, transport defective glycoprotein (gp57). Only a small proportion of gp57 underwent further oligosaccharide processing. Intracellular gp57 remained predominantly monomeric and only a small proportion of gp57 (and its processed forms) formed disulfide-linked dimers and trimers which resembled those formed by SFFV gp52. Processed forms of gp57 were found on the cell surfaces and in culture fluids. The extracellular forms had a faster electrophoretic mobility than the intracellular-processed forms of gp57. These results indicate that the 585-bp deletion found in SFFV env gene is responsible for the folding, transport, and secretion of gp52. Retroviral vectors carrying the mutant MCFV env gene were nonpathogenic (or weakly pathogenic) in adult mice. The results indicate that the 585-bp deletion, although essential, is not the sole determinant of SFFV-induced disease in adult mice.
Srinivas
R V
RV
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Tucker
S P
SP
Kilpatrick
D R
DR
Compans
R W
RW
D016475:3T3 Cells; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004220:Disulfides; D000091342:Endoplasmic Reticulum Chaperone BiP; D005455:Fluorescent Antibody Technique; D015752:Genes, env; D006023:Glycoproteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D051379:Mice; D008908:Mink Cell Focus-Inducing Viruses / Q000235:genetics; D018832:Molecular Chaperones; D009154:Mutation; D013155:Spleen Focus-Forming Viruses / Q000235:genetics* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D004220:Disulfides; D000091342:Endoplasmic Reticulum Chaperone BiP; D006023:Glycoproteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D014759:Viral Envelope Proteins