TY - JOUR
T1 - Role of a membrane glycoprotein in friend virus-induced erythroleukemia
T2 - Studies of mutant and revertant viruses
AU - Machida, Curtis A.
AU - Bestwick, Richard K.
AU - Boswell, Bruce A.
AU - Kabat, David
N1 - Funding Information:
We are indebted to our colleague Jing-Po Li for allowing us to cite his unpublished nucleotide sequence results and for stimulating discussions. In addition, we thankfully acknowledgeD avid Linder for continued helpful advice concerning the characteristics of cancer and the pathologic analysis of tissue sections and Jennifer Au for expert technical assistance.R .K.B. is a Special Fellow of the Leukemia Society of America. This research was supported by U. S. P.H.S. Grant CA 35810a nd in part by American Cancer Society Grant MV-169.
PY - 1985/7/15
Y1 - 1985/7/15
N2 - We previously reported the isolation and characterization of spontaneous, transmissible mutants of Friend spleen focus-forming virus (SFFV) that are nonpathogenic in adult NIH/Swiss mice and that contain abnormalities in nonoverlapping regions of their envelope glycoprotein (env) genes (M. Ruta, R. Bestwick, C. Machida, and D. Kabat, 1983,Proc. Natl. Acad. Sci. USA 80, 4704-4708). In newborn NIH/Swiss mice, these mutant SFFVs form revertants that are pathogenic in mice of all ages. At least two of three studied revertants contain second site env mutations which affect the sizes and proteolytic fragmentation patterns of their encoded glycoproteins. A variety of structural and genetic evidence suggests that the xenotropic- and ecotropic-related regions of the SFFV glycoprotein fold into separate globular domains that are connected by a flexible proline-rich joint. A glutamyl peptide bond within this joint is exceptionally susceptible to cleavage with Staphylococcus aureus V8 protease. Moreover, disulfide bonds occur within the xenotropic-related domain, but not between the globular domains. These results provide strong additional evidence that the env gene is required for SFFV pathogenesis, and they provide a new system for identifying the features of glycoprotein structure and localization which are essential for its leukemogenic activity.
AB - We previously reported the isolation and characterization of spontaneous, transmissible mutants of Friend spleen focus-forming virus (SFFV) that are nonpathogenic in adult NIH/Swiss mice and that contain abnormalities in nonoverlapping regions of their envelope glycoprotein (env) genes (M. Ruta, R. Bestwick, C. Machida, and D. Kabat, 1983,Proc. Natl. Acad. Sci. USA 80, 4704-4708). In newborn NIH/Swiss mice, these mutant SFFVs form revertants that are pathogenic in mice of all ages. At least two of three studied revertants contain second site env mutations which affect the sizes and proteolytic fragmentation patterns of their encoded glycoproteins. A variety of structural and genetic evidence suggests that the xenotropic- and ecotropic-related regions of the SFFV glycoprotein fold into separate globular domains that are connected by a flexible proline-rich joint. A glutamyl peptide bond within this joint is exceptionally susceptible to cleavage with Staphylococcus aureus V8 protease. Moreover, disulfide bonds occur within the xenotropic-related domain, but not between the globular domains. These results provide strong additional evidence that the env gene is required for SFFV pathogenesis, and they provide a new system for identifying the features of glycoprotein structure and localization which are essential for its leukemogenic activity.
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U2 - 10.1016/0042-6822(85)90314-9
DO - 10.1016/0042-6822(85)90314-9
M3 - Article
C2 - 2998041
AN - SCOPUS:0021931241
SN - 0042-6822
VL - 144
SP - 158
EP - 172
JO - Virology
JF - Virology
IS - 1
ER -