This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jolly, D J Articles by Friedmann, T Search for Related Content PubMed PubMed Citation Articles by Jolly, D J Articles by Friedmann, T

 Previous Article  |  Next Article 

Mol Cell Biol. 1986 April; 6(4): 1141-1147

Variable stability of a selectable provirus after retroviral vector gene transfer into human cells.

ABSTRACT

Human lymphoblasts deficient in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) were infected with an amphotropic helper-free retroviral vector expressing human HPRT cDNA. The stability and expression of the HPRT provirus in five cell lines with different proviral integration sites were examined by determining HPRT mutation and reversion frequencies and by blot hybridization studies. Mutation to the HPRT-negative phenotype occurred at frequencies of approximately 4 X 10(-5) to 3 X 10(-6) per generation. Most mutations in each of the five cell lines were associated with partial or complete deletions or rearrangements of the provirus. Several mutants retained a grossly intact HPRT provirus, and in one such mutant HPRT shutdown resulted from a revertible epigenetic mechanism that was not associated with global changes in proviral methylation. Therefore, mutation and shutdown of the HPRT provirus in human lymphoblasts result from mechanisms similar to those reported for several other avian and mammalian replication-competent retroviruses.

This article has been cited by other articles:

• Young, W.-B., Lindberg, G. L., Link, C. J. Jr. (2000). DNA Methylation of Helper Virus Increases Genetic Instability of Retroviral Vector Producer Cells. J. Virol. 74: 3177-3187 [Abstract] [Full Text]  
• Zhang, R., Minemura, K., De Groot, L. J. (1998). Immunotherapy for Medullary Thyroid Carcinoma by a Replication-Defective Adenovirus Transducing Murine Interleukin-2. Endocrinology 139: 601-608 [Abstract] [Full Text]  
• Friedmann, T (1989). Progress toward human gene therapy. Science 244: 1275-1281 [Abstract]  
• Huang, H., Yee, J., Shew, J., Chen, P., Bookstein, R, Friedmann, T, Lee, E., Lee, W. (1988). Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells. Science 242: 1563-1566 [Abstract]  
• Preston, B., Poiesz, B., Loeb, L. (1988). Fidelity of HIV-1 reverse transcriptase. Science 242: 1168-1171 [Abstract]