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. 1996 Mar;70(3):1804–1809. doi: 10.1128/jvi.70.3.1804-1809.1996

A novel murine retrovirus identified during testing for helper virus in human gene transfer trials.

A D Miller 1, L Bonham 1, J Alfano 1, H P Kiem 1, T Reynolds 1, G Wolgamot 1
PMCID: PMC190007  PMID: 8627704

Abstract

An important requirement for the use of retroviral vectors in human gene transfer experiments is the avoidance of human exposure to replication-competent (helper) retroviruses. To meet this requirement, we used a sensitive marker rescue assay for helper virus to screen vector-transduced cells prior to reinfusion into patients. This assay utilized Mus dunni cells harboring a retroviral vector that can be rescued by helper retroviruses. The assay indicated the presence of helper virus in medium exposed to hematopoietic cells from all patients tested, including six patients with various cancers and one patient with Gaucher's disease, whether or not the patient cells had been exposed to retroviral vectors. All of the helper viruses were in a single interference group. We have now shown that treatment of the M. dunni marker rescue assay cells with 5-iodo-2'-deoxyuridine or hydrocortisone can activate production of an apparently identical helper virus, which we have named M. dunni endogenous virus (MDEV). Thus, production of virus in the assays of patient materials was likely due to exposure of the marker rescue assay cells to the hydrocortisone present in the hematopoietic cell growth medium. MDEV does not belong to any of the known murine leukemia virus groups by interference analysis, and we have called the new group multitropic because of the wide range of cells from different species that MDEV can infect.

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Selected References

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  1. Armentano D., Yu S. F., Kantoff P. W., von Ruden T., Anderson W. F., Gilboa E. Effect of internal viral sequences on the utility of retroviral vectors. J Virol. 1987 May;61(5):1647–1650. doi: 10.1128/jvi.61.5.1647-1650.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bauer T. R., Jr, Miller A. D., Hickstein D. D. Improved transfer of the leukocyte integrin CD18 subunit into hematopoietic cell lines by using retroviral vectors having a gibbon ape leukemia virus envelope. Blood. 1995 Sep 15;86(6):2379–2387. [PubMed] [Google Scholar]
  3. Bunnell B. A., Muul L. M., Donahue R. E., Blaese R. M., Morgan R. A. High-efficiency retroviral-mediated gene transfer into human and nonhuman primate peripheral blood lymphocytes. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7739–7743. doi: 10.1073/pnas.92.17.7739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chattopadhyay S. K., Lander M. R., Gupta S., Rands E., Lowy D. R. Origin of mink cytopathic focus-forming (MCF) viruses:comparison with ecotropic and xenotropic murine leukemia virus genomes. Virology. 1981 Sep;113(2):465–483. doi: 10.1016/0042-6822(81)90175-6. [DOI] [PubMed] [Google Scholar]
  5. Cloyd M. W., Hartley J. W., Rowe W. P. Genetic study of lymphoma induction by AKR mink cell focus-inducing virus in AKR x NFS crosses. J Exp Med. 1981 Aug 1;154(2):450–457. doi: 10.1084/jem.154.2.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dunn K. J., Yuan C. C., Blair D. G. A phenotypic host range alteration determines RD114 virus restriction in feline embryonic cells. J Virol. 1993 Aug;67(8):4704–4711. doi: 10.1128/jvi.67.8.4704-4711.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fields-Berry S. C., Halliday A. L., Cepko C. L. A recombinant retrovirus encoding alkaline phosphatase confirms clonal boundary assignment in lineage analysis of murine retina. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):693–697. doi: 10.1073/pnas.89.2.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fischinger P. J., Nomura S., Bolognesi D. P. A novel murine oncornavirus with dual eco- and xenotropic properties. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5150–5155. doi: 10.1073/pnas.72.12.5150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Haapala D. K., Robey W. G., Oroszlan S. D., Tsai W. P. Isolation from cats of an endogenous type C virus with a novel envelope glycoprotein. J Virol. 1985 Mar;53(3):827–833. doi: 10.1128/jvi.53.3.827-833.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huu Duc-Nguyen, Rosenblum E. N., Zeigel R. F. Persistent infection of a rat kidney cell line with Rauscher murine leukemia virus. J Bacteriol. 1966 Oct;92(4):1133–1140. doi: 10.1128/jb.92.4.1133-1140.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lander M. R., Chattopadhyay S. K. A Mus dunni cell line that lacks sequences closely related to endogenous murine leukemia viruses and can be infected by ectropic, amphotropic, xenotropic, and mink cell focus-forming viruses. J Virol. 1984 Nov;52(2):695–698. doi: 10.1128/jvi.52.2.695-698.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Miller A. D., Buttimore C. Redesign of retrovirus packaging cell lines to avoid recombination leading to helper virus production. Mol Cell Biol. 1986 Aug;6(8):2895–2902. doi: 10.1128/mcb.6.8.2895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Miller A. D., Garcia J. V., von Suhr N., Lynch C. M., Wilson C., Eiden M. V. Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus. J Virol. 1991 May;65(5):2220–2224. doi: 10.1128/jvi.65.5.2220-2224.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller A. D., Law M. F., Verma I. M. Generation of helper-free amphotropic retroviruses that transduce a dominant-acting, methotrexate-resistant dihydrofolate reductase gene. Mol Cell Biol. 1985 Mar;5(3):431–437. doi: 10.1128/mcb.5.3.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miller A. D., Rosman G. J. Improved retroviral vectors for gene transfer and expression. Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90. [PMC free article] [PubMed] [Google Scholar]
  16. Miller A. D., Verma I. M. Two base changes restore infectivity to a noninfectious molecular clone of Moloney murine leukemia virus (pMLV-1). J Virol. 1984 Jan;49(1):214–222. doi: 10.1128/jvi.49.1.214-222.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miller D. G., Edwards R. H., Miller A. D. Cloning of the cellular receptor for amphotropic murine retroviruses reveals homology to that for gibbon ape leukemia virus. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):78–82. doi: 10.1073/pnas.91.1.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miller D. G., Miller A. D. A family of retroviruses that utilize related phosphate transporters for cell entry. J Virol. 1994 Dec;68(12):8270–8276. doi: 10.1128/jvi.68.12.8270-8276.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miller D. G., Miller A. D. Tunicamycin treatment of CHO cells abrogates multiple blocks to retrovirus infection, one of which is due to a secreted inhibitor. J Virol. 1992 Jan;66(1):78–84. doi: 10.1128/jvi.66.1.78-84.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. O'Neill R. R., Buckler C. E., Theodore T. S., Martin M. A., Repaske R. Envelope and long terminal repeat sequences of a cloned infectious NZB xenotropic murine leukemia virus. J Virol. 1985 Jan;53(1):100–106. doi: 10.1128/jvi.53.1.100-106.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ott D., Friedrich R., Rein A. Sequence analysis of amphotropic and 10A1 murine leukemia viruses: close relationship to mink cell focus-inducing viruses. J Virol. 1990 Feb;64(2):757–766. doi: 10.1128/jvi.64.2.757-766.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ott D., Rein A. Basis for receptor specificity of nonecotropic murine leukemia virus surface glycoprotein gp70SU. J Virol. 1992 Aug;66(8):4632–4638. doi: 10.1128/jvi.66.8.4632-4638.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schuening F., Miller A. D., Torok-Storb B., Bensinger W., Storb R., Reynolds T., Fisher L., Buckner C. D., Appelbaum F. R. Study on contribution of genetically marked peripheral blood repopulating cells to hematopoietic reconstitution after transplantation. Hum Gene Ther. 1994 Dec;5(12):1523–1534. doi: 10.1089/hum.1994.5.12-1523. [DOI] [PubMed] [Google Scholar]
  24. Sommerfelt M. A., Weiss R. A. Receptor interference groups of 20 retroviruses plating on human cells. Virology. 1990 May;176(1):58–69. doi: 10.1016/0042-6822(90)90230-o. [DOI] [PubMed] [Google Scholar]
  25. von Kalle C., Kiem H. P., Goehle S., Darovsky B., Heimfeld S., Torok-Storb B., Storb R., Schuening F. G. Increased gene transfer into human hematopoietic progenitor cells by extended in vitro exposure to a pseudotyped retroviral vector. Blood. 1994 Nov 1;84(9):2890–2897. [PubMed] [Google Scholar]

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