Expression of a truncated retroviral envelope gene enhances expression of normal cellular phenotypes.
The envelope gene of Moloney murine leukemia virus (Mo-MLV) and its various functional domains have been studied extensively but not as much in terms of their biological effects on cell growth. In this study, we report the biological characterization of a truncated Mo-MLV envelope gene, LN11, which is devoid of a signal peptide. Its expression in various cell types, as compared to the control, enabled the transduced cells to assume a more normal phenotype, which is defined by an increase in contact inhibition and factor dependence, as well as reduced tumorigenicity. LN11-transduced fibroblasts exhibited a higher degree of contact inhibition, assumed a more flattened morphology and were more adherent compared to the control. In v-abl transformed hematopoietic cells, expression of LN11 resulted in slower cell growth, which was due to an enhanced dependence on exogenous growth factors. Enforced expression of LN11 also resulted in a slower rate of tumor development and a reduced tumor load. Thus, modification of a retroviral genome could have a significant impact on cell growth and development. This is one example where we need to consider the safety issue carefully when constructing retrovirus vectors for gene therapy.
Chen
H
H
Department of Pathology and Laboratory Medicine, Fels Institute, Temple University School of Medicine, Philadelphia, PA 19104, USA.
Chung
S W
SW
Wong
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D016313:Genes, abl; D015752:Genes, env; D005822:Genetic Vectors; D051379:Mice; D008819:Mice, Nude; D008979:Moloney murine leukemia virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D009374:Neoplasms, Experimental / Q000209:etiology; D010641:Phenotype; D017384:Sequence Deletion; D014161:Transduction, Genetic
D004279:DNA, Viral