Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1996 Aug;70(8):5651–5657. doi: 10.1128/jvi.70.8.5651-5657.1996

Homologous and nonhomologous retroviral recombinations are both involved in the transfer by infectious particles of defective avian leukosis virus-derived transcomplementing genomes.

A Girod 1, A Drynda 1, F L Cosset 1, G Verdier 1, C Ronfort 1
PMCID: PMC190528  PMID: 8764082

Abstract

We previously described avian leukosis virus-based packaging cell lines that produce stocks of retroviral vectors in which replication-competent viruses were not detectable. However, following infection of target cells with these retroviral stocks, we recently obtained colonies resulting from the transmission of recombinant genomes. Here, we have analyzed their genetic structure and shown that (i) each of them results from recombination between the packaging- and integration-defective transcomplementing genomes and the retroviral vector; (ii) recombination probably occurred during the reverse transcription step, involving strand switching of the reverse transcription growing point from the infectious retroviral vector to the transcomplementing RNA; and (iii) sequence identity and nonhomologous sequences were both used for the strand switching.

Full Text

The Full Text of this article is available as a PDF (299.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronoff R., Linial M. Specificity of retroviral RNA packaging. J Virol. 1991 Jan;65(1):71–80. doi: 10.1128/jvi.65.1.71-80.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bestwick R. K., Kozak S. L., Kabat D. Overcoming interference to retroviral superinfection results in amplified expression and transmission of cloned genes. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5404–5408. doi: 10.1073/pnas.85.15.5404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bizub D., Katz R. A., Skalka A. M. Nucleotide sequence of noncoding regions in Rous-associated virus-2: comparisons delineate conserved regions important in replication and oncogenesis. J Virol. 1984 Feb;49(2):557–565. doi: 10.1128/jvi.49.2.557-565.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coffin J. M. Structure, replication, and recombination of retrovirus genomes: some unifying hypotheses. J Gen Virol. 1979 Jan;42(1):1–26. doi: 10.1099/0022-1317-42-1-1. [DOI] [PubMed] [Google Scholar]
  5. Cone R. D., Mulligan R. C. High-efficiency gene transfer into mammalian cells: generation of helper-free recombinant retrovirus with broad mammalian host range. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6349–6353. doi: 10.1073/pnas.81.20.6349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cosset F. L., Girod A., Flamant F., Drynda A., Ronfort C., Valsesia S., Molina R. M., Faure C., Nigon V. M., Verdier G. Use of helper cells with two host ranges to generate high-titer retroviral vectors. Virology. 1993 Mar;193(1):385–395. doi: 10.1006/viro.1993.1135. [DOI] [PubMed] [Google Scholar]
  7. Cosset F. L., Legras C., Chebloune Y., Savatier P., Thoraval P., Thomas J. L., Samarut J., Nigon V. M., Verdier G. A new avian leukosis virus-based packaging cell line that uses two separate transcomplementing helper genomes. J Virol. 1990 Mar;64(3):1070–1078. doi: 10.1128/jvi.64.3.1070-1078.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cosset F. L., Legras C., Thomas J. L., Molina R. M., Chebloune Y., Faure C., Nigon V. M., Verdier G. Improvement of avian leukosis virus (ALV)-based retrovirus vectors by using different cis-acting sequences from ALVs. J Virol. 1991 Jun;65(6):3388–3394. doi: 10.1128/jvi.65.6.3388-3394.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cosset F. L., Ronfort C., Molina R. M., Flamant F., Drynda A., Benchaibi M., Valsesia S., Nigon V. M., Verdier G. Packaging cells for avian leukosis virus-based vectors with various host ranges. J Virol. 1992 Sep;66(9):5671–5676. doi: 10.1128/jvi.66.9.5671-5676.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Danos O., Mulligan R. C. Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6460–6464. doi: 10.1073/pnas.85.17.6460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dornburg R., Temin H. M. Retroviral vector system for the study of cDNA gene formation. Mol Cell Biol. 1988 Jun;8(6):2328–2334. doi: 10.1128/mcb.8.6.2328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dougherty J. P., Wisniewski R., Yang S. L., Rhode B. W., Temin H. M. New retrovirus helper cells with almost no nucleotide sequence homology to retrovirus vectors. J Virol. 1989 Jul;63(7):3209–3212. doi: 10.1128/jvi.63.7.3209-3212.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Girod A., Cosset F. L., Verdier G., Ronfort C. Analysis of ALV-based packaging cell lines for production of contaminant defective viruses. Virology. 1995 Jun 1;209(2):671–675. doi: 10.1006/viro.1995.1302. [DOI] [PubMed] [Google Scholar]
  14. Goodrich D. W., Duesberg P. H. Retroviral recombination during reverse transcription. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2052–2056. doi: 10.1073/pnas.87.6.2052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hajjar A. M., Linial M. L. A model system for nonhomologous recombination between retroviral and cellular RNA. J Virol. 1993 Jul;67(7):3845–3853. doi: 10.1128/jvi.67.7.3845-3853.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hodgson C. P., Arora P., Fisk R. Z. Nucleotide sequence of the long terminal repeat of the avian retrovirus RAV-1: evolution of avian retroviruses. Nucleic Acids Res. 1987 Mar 11;15(5):2393–2393. doi: 10.1093/nar/15.5.2393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hu W. S., Temin H. M. Genetic consequences of packaging two RNA genomes in one retroviral particle: pseudodiploidy and high rate of genetic recombination. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1556–1560. doi: 10.1073/pnas.87.4.1556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jones J. S., Allan R. W., Temin H. M. One retroviral RNA is sufficient for synthesis of viral DNA. J Virol. 1994 Jan;68(1):207–216. doi: 10.1128/jvi.68.1.207-216.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Junghans R. P., Boone L. R., Skalka A. M. Retroviral DNA H structures: displacement-assimilation model of recombination. Cell. 1982 Aug;30(1):53–62. doi: 10.1016/0092-8674(82)90011-3. [DOI] [PubMed] [Google Scholar]
  20. Levine K. L., Steiner B., Johnson K., Aronoff R., Quinton T. J., Linial M. L. Unusual features of integrated cDNAs generated by infection with genome-free retroviruses. Mol Cell Biol. 1990 May;10(5):1891–1900. doi: 10.1128/mcb.10.5.1891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Linial M. Creation of a processed pseudogene by retroviral infection. Cell. 1987 Apr 10;49(1):93–102. doi: 10.1016/0092-8674(87)90759-8. [DOI] [PubMed] [Google Scholar]
  22. Markowitz D., Goff S., Bank A. A safe packaging line for gene transfer: separating viral genes on two different plasmids. J Virol. 1988 Apr;62(4):1120–1124. doi: 10.1128/jvi.62.4.1120-1124.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Miller A. D. Retrovirus packaging cells. Hum Gene Ther. 1990 Spring;1(1):5–14. doi: 10.1089/hum.1990.1.1-5. [DOI] [PubMed] [Google Scholar]
  24. Moscovici C., Moscovici M. G., Jimenez H., Lai M. M., Hayman M. J., Vogt P. K. Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail. Cell. 1977 May;11(1):95–103. doi: 10.1016/0092-8674(77)90320-8. [DOI] [PubMed] [Google Scholar]
  25. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Muenchau D. D., Freeman S. M., Cornetta K., Zwiebel J. A., Anderson W. F. Analysis of retroviral packaging lines for generation of replication-competent virus. Virology. 1990 May;176(1):262–265. doi: 10.1016/0042-6822(90)90251-l. [DOI] [PubMed] [Google Scholar]
  27. Pathak V. K., Temin H. M. 5-Azacytidine and RNA secondary structure increase the retrovirus mutation rate. J Virol. 1992 May;66(5):3093–3100. doi: 10.1128/jvi.66.5.3093-3100.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ronfort C., Afanassieff M., Chebloune Y., Dambrine G., Nigon V. M., Verdier G. Identification and structure analysis of endogenous proviral sequences in a Brown Leghorn chicken strain. Poult Sci. 1991 Oct;70(10):2161–2175. doi: 10.3382/ps.0702161. [DOI] [PubMed] [Google Scholar]
  29. Ronfort C., Girod A., Cosset F. L., Legras C., Nigon V. M., Chebloune Y., Verdier G. Defective retroviral endogenous RNA is efficiently transmitted by infectious particles produced on an avian retroviral vector packaging cell line. Virology. 1995 Feb 20;207(1):271–275. doi: 10.1006/viro.1995.1076. [DOI] [PubMed] [Google Scholar]
  30. Savatier P., Bagnis C., Thoraval P., Poncet D., Belakebi M., Mallet F., Legras C., Cosset F. L., Thomas J. L., Chebloune Y. Generation of a helper cell line for packaging avian leukosis virus-based vectors. J Virol. 1989 Feb;63(2):513–522. doi: 10.1128/jvi.63.2.513-522.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Scadden D. T., Fuller B., Cunningham J. M. Human cells infected with retrovirus vectors acquire an endogenous murine provirus. J Virol. 1990 Jan;64(1):424–427. doi: 10.1128/jvi.64.1.424-427.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stuhlmann H., Berg P. Homologous recombination of copackaged retrovirus RNAs during reverse transcription. J Virol. 1992 Apr;66(4):2378–2388. doi: 10.1128/jvi.66.4.2378-2388.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Swain A., Coffin J. M. Mechanism of transduction by retroviruses. Science. 1992 Feb 14;255(5046):841–845. doi: 10.1126/science.1371365. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES