Abstract
We have studied the virus produced by a clone, termed 8A, that was isolated from a culture of murine sarcoma virus-transformed mouse cells after superinfection with Moloney murine leukemia virus (MuLV-M). Clone 8A produced high levels of type C virus particles, but only a low titer of infectious murine sarcoma virus and almost no infectious MuLV. When fresh cultures of mouse cells were infected with undiluted clone 8A culture fluids, they released no detectable pogeny virus for several weeks after infection. Fully infectious MuLV was then produced in these cultures. This virus was indistinguishable from MuLV-M by nucleic acid hybridization tests and in its insensitivity to Fv-1 restriction. It also induced thymic lymphomas in BALB/c mice. To explain these results, we propose that cone 8A is infected with a replication-defective variant of MuLV-M. Particles produced by clone 8A, containing this defective genome, can establish an infection in fresh cells but cannot produce progency virus at detectable levels. Several weeks after infection, the defect in the viral genome is corrected by back-mutation or by recombination with endogenous viral genomes, resulting in the formation of fully infectious progeny MuLV. The progeny MuLV'S that arose in two different experiments were found to be genetically different from each other. This is consistent with the hypothesis that, in each experiment, the progeny virus is formed clone 8A cells and assayed for infectivity by the calcium phosphate transfection technique. No detectable MuLV was produced by cells treated with this DNA. This finding, along with positive results obtained in control experiments, indicates that clone 8A cells do not contain a normal MuLV provirus.
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aaronson S. A., Bassin R. H., Weaver C. Comparison of murine sarcoma viruses in nonproducer and S + L - -transformed cells. J Virol. 1972 Apr;9(4):701–704. doi: 10.1128/jvi.9.4.701-704.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aaronson S. A., Todaro G. J. Development of 3T3-like lines from Balb-c mouse embryo cultures: transformation susceptibility to SV40. J Cell Physiol. 1968 Oct;72(2):141–148. doi: 10.1002/jcp.1040720208. [DOI] [PubMed] [Google Scholar]
- Bassin R. H., Gerwin B. I., Duran-Troise G., Gisselbrecht S., Rein A. Murine sarcoma virus pseudotypes acquire a determinant specifying N or B tropism from leukaemia virus during rescue. Nature. 1975 Jul 17;256(5514):223–225. doi: 10.1038/256223a0. [DOI] [PubMed] [Google Scholar]
- Bassin R. H., Phillips L. A., Kramer M. J., Haapala D. K., Peebles P. T., Nomura S., Fischinger P. J. Transformation of mouse 3T3 cells by murine sarcoma virus: release of virus-like particles in the absence of replicating murine leukemia helper virus. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1520–1524. doi: 10.1073/pnas.68.7.1520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bassin R. H., Tuttle N., Fischinger P. J. Isolation of murine sarcoma virus-transformed mouse cells which are negative for leukemia virus from agar suspension cultures. Int J Cancer. 1970 Jul 15;6(1):95–107. doi: 10.1002/ijc.2910060114. [DOI] [PubMed] [Google Scholar]
- Bassin R. H., Tuttle N., Fischinger P. J. Rapid cell culture assay technic for murine leukaemia viruses. Nature. 1971 Feb 19;229(5286):564–566. doi: 10.1038/229564b0. [DOI] [PubMed] [Google Scholar]
- Benveniste R. E., Lieber M. M., Todaro G. J. A distinct class of inducible murine type-C viruses that replicates in the rabbit SIRC cell line. Proc Natl Acad Sci U S A. 1974 Mar;71(3):602–606. doi: 10.1073/pnas.71.3.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benveniste R. E., Scolnick E. M. RNA in mammalian sarcoma virus transformed nonproducer cells homologous to murine leukemia virus RNA. Virology. 1973 Feb;51(2):370–382. doi: 10.1016/0042-6822(73)90436-4. [DOI] [PubMed] [Google Scholar]
- Bryant M. L., Klement V. Clonal heterogeneity of wild mouse leukemia viruses: host ranges and antigenicity. Virology. 1976 Sep;73(2):532–536. doi: 10.1016/0042-6822(76)90415-3. [DOI] [PubMed] [Google Scholar]
- Callahan R., Benveniste R. E., Lieber M. M., Todaro G. J. Nucleic acid homology of murine type-C viral genes. J Virol. 1974 Dec;14(6):1394–1403. doi: 10.1128/jvi.14.6.1394-1403.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- East J. L., Knesek J. E., Chan J. C., Dmochowski L. Quantitative nucleotide sequence relationships of mammalian RNA tumor viruses. J Virol. 1975 Jun;15(6):1396–1408. doi: 10.1128/jvi.15.6.1396-1408.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fischinger P. J., Moore C. O., O'Connor T. E. Isolation and identification of a helper virus found in the Moloney sarcoma-leukemia virus complex. J Natl Cancer Inst. 1969 Apr;42(4):605–622. [PubMed] [Google Scholar]
- 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]
- Fischinger P. J., Nomura S., Tuttle-Fuller N., Dunn K. J. Revertants of mouse cells transformed by murine sarcoma virus. 3. Metastable expression of virus functions in revertants retransformed by murine sarcoma virus. Virology. 1974 May;59(1):217–229. [PubMed] [Google Scholar]
- Fischinger P. J., O'Connor T. E. Tissue culture assay of helper activity of murine leukemia virus for murine sarcoma virus. J Natl Cancer Inst. 1968 Jun;40(6):1199–1212. [PubMed] [Google Scholar]
- Fischinger P. J., Schaefer W., Seifert E. Detection of some murine leukemia virus antigens in virus particles derived from 3T3 cells transformed only by murine sarcoma virus. Virology. 1972 Jan;47(1):229–235. doi: 10.1016/0042-6822(72)90254-1. [DOI] [PubMed] [Google Scholar]
- Gerwin B. I., Levin J. G. Interactions of murine leukemia virus core components: characterization of reverse transcriptase packaged in the absence of 70S genomic RNA. J Virol. 1977 Nov;24(2):478–488. doi: 10.1128/jvi.24.2.478-488.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gisselbrecht S., Bassin R. H., Gerwin B. I., Rein A. Dual susceptibility of A 3T3 mouse cell line to infection by N- and B-tropic murine leukemia virus: apparent lack of expression of the FV-1 gene. Int J Cancer. 1974 Jul 15;14(1):106–113. doi: 10.1002/ijc.2910140113. [DOI] [PubMed] [Google Scholar]
- Glisin V., Crkvenjakov R., Byus C. Ribonucleic acid isolated by cesium chloride centrifugation. Biochemistry. 1974 Jun 4;13(12):2633–2637. doi: 10.1021/bi00709a025. [DOI] [PubMed] [Google Scholar]
- Goldsby R. A., Zipser E. The isolation and replica plating of mammalian cell clones. Exp Cell Res. 1969 Feb;54(2):271–275. doi: 10.1016/0014-4827(69)90250-x. [DOI] [PubMed] [Google Scholar]
- Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
- Hartley J. W., Rowe W. P. Clonal cells lines from a feral mouse embryo which lack host-range restrictions for murine leukemia viruses. Virology. 1975 May;65(1):128–134. doi: 10.1016/0042-6822(75)90013-6. [DOI] [PubMed] [Google Scholar]
- Hartley J. W., Rowe W. P., Huebner R. J. Host-range restrictions of murine leukemia viruses in mouse embryo cell cultures. J Virol. 1970 Feb;5(2):221–225. doi: 10.1128/jvi.5.2.221-225.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartley J. W., Rowe W. P. Naturally occurring murine leukemia viruses in wild mice: characterization of a new "amphotropic" class. J Virol. 1976 Jul;19(1):19–25. doi: 10.1128/jvi.19.1.19-25.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartley J. W., Rowe W. P. Production of altered cell foci in tissue culture by defective Moloney sarcoma virus particles. Proc Natl Acad Sci U S A. 1966 Apr;55(4):780–786. doi: 10.1073/pnas.55.4.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartley J. W., Wolford N. K., Old L. J., Rowe W. P. A new class of murine leukemia virus associated with development of spontaneous lymphomas. Proc Natl Acad Sci U S A. 1977 Feb;74(2):789–792. doi: 10.1073/pnas.74.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayward W. S., Hanafusa H. Recombination between endogenous and exogenous RNA tumor virus genes as analyzed by nucleic acid hybridization. J Virol. 1975 Jun;15(6):1367–1377. doi: 10.1128/jvi.15.6.1367-1377.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hill M., Hillova J. Virus recovery in chicken cells tested with Rous sarcoma cell DNA. Nat New Biol. 1972 May 10;237(71):35–39. doi: 10.1038/newbio237035a0. [DOI] [PubMed] [Google Scholar]
- Hopkins N., Jolicoeur P. Variants of N-tropic leukemia virus derived from BALB/c mice. J Virol. 1975 Oct;16(4):991–999. doi: 10.1128/jvi.16.4.991-999.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hopkins N., Schindler J., Hynes R. Six-NB-tropic murine leukemia viruses derived from a B-tropic virus of BALB/c have altered p30. J Virol. 1977 Jan;21(1):309–318. doi: 10.1128/jvi.21.1.309-318.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Jainchill J. L., Aaronson S. A., Todaro G. J. Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells. J Virol. 1969 Nov;4(5):549–553. doi: 10.1128/jvi.4.5.549-553.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jolicoeur P., Baltimore D. Effect of Fv-1 gene product on synthesis of N-tropic and B-tropic murine leukemia viral RNA. Cell. 1976 Jan;7(1):33–39. doi: 10.1016/0092-8674(76)90252-x. [DOI] [PubMed] [Google Scholar]
- Kashmiri S. V., Rein A., Bassin R. H., Gerwin B. I., Gisselbrecht S. Donation of N- or B-tropic phenotype to NB-tropic murine leukemia virus during mixed infections. J Virol. 1977 Jun;22(3):626–633. doi: 10.1128/jvi.22.3.626-633.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller N. R., Saxinger W. C., Reitz M. S., Gallagher R. E., Wu A. M., Gallo R. C., Gillespie D. Systematics of RNA tumor viruses and virus-like particles of human origin. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3177–3181. doi: 10.1073/pnas.71.8.3177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peebles P. T., Gerwin B. I., Scolnick E. M. Murine sarcoma virus defectiveness: serological detection of only helper virus reverse transcriptase in sarcoma virus rescued from nonmurine S + L-cells. Virology. 1976 Apr;70(2):313–323. doi: 10.1016/0042-6822(76)90274-9. [DOI] [PubMed] [Google Scholar]
- Rapp U. R., Nowinski R. C. Endogenous ecotropic mouse type C viruses deficient in replication and production of XC plaques. J Virol. 1976 May;18(2):411–417. doi: 10.1128/jvi.18.2.411-417.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rasheed S., Gardner M. B., Chan E. Amphotropic host range of naturally occuring wild mouse leukemia viruses. J Virol. 1976 Jul;19(1):13–18. doi: 10.1128/jvi.19.1.13-18.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rein A., Kashmiri S. V., Bassin R. H., Gerwin B. L., Duran-Troise G. Phenotypic mixing between N- and B-tropic murine leukemia viruses: infectious particles with dual sensitivity to Fv-1 restriction. Cell. 1976 Mar;7(3):373–379. doi: 10.1016/0092-8674(76)90166-5. [DOI] [PubMed] [Google Scholar]
- Reznikoff C. A., Brankow D. W., Heidelberger C. Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res. 1973 Dec;33(12):3231–3238. [PubMed] [Google Scholar]
- Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
- Schindler J., Hynes R., Hopkins N. Evidence for recombination between N- and B-tropic murine leukemia viruses: analysis of three virion proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. J Virol. 1977 Sep;23(3):700–700. doi: 10.1128/jvi.23.3.700-.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scolnick E. M., Stephenson J. R., Aaronson S. A. Isolation of temperature-sensitive mutants of murine sarcoma virus. J Virol. 1972 Oct;10(4):653–657. doi: 10.1128/jvi.10.4.653-657.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stephenson J. R., Aaronson S. A. A genetic locus for inducibility of C-type in BALB-c cells: the effect of a nonlinked regulatory gene on detection of virus after chemical activation. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2798–2801. doi: 10.1073/pnas.69.10.2798. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stephenson J. R., Aaronson S. A. Characterization of temperature-sensitive mutants of murine leukemia virus. Virology. 1973 Jul;54(1):53–59. doi: 10.1016/0042-6822(73)90113-x. [DOI] [PubMed] [Google Scholar]
- Stephenson J. R., Aaronson S. A. Temperature-sensitive mutants of murine leukemia virus. 3. Mutants defective in helper functions for sarcoma virus fixation. Virology. 1974 Mar;58(1):294–297. doi: 10.1016/0042-6822(74)90163-9. [DOI] [PubMed] [Google Scholar]
- Stephenson J. R., Anderson G. R., Tronick S. R., Aaronson S. A. Evidence for genetic recombination between endogenous and exogenous mouse RNA type C viruses. Cell. 1974 Jun;2(2):87–94. doi: 10.1016/0092-8674(74)90096-8. [DOI] [PubMed] [Google Scholar]
- Stephenson J. R., Reynolds R. K., Aaronson S. A. Isolation of temperature-sensitive mutants of murine leukemia virus. Virology. 1972 Jun;48(3):749–756. doi: 10.1016/0042-6822(72)90158-4. [DOI] [PubMed] [Google Scholar]
- Tronick S. R., Stephenson J. R., Verma I. M., Aaronson S. A. Thermolabile reverse transcriptase of a mammalian leukemia virus mutant temperature sensitive in its replication and sarcoma virus helper functions. J Virol. 1975 Dec;16(6):1476–1482. doi: 10.1128/jvi.16.6.1476-1482.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Troxler D. H., Boyars J. K., Parks W. P., Scolnick E. M. Friend strain of spleen focus-forming virus: a recombinant between mouse type C ecotropic viral sequences and sequences related to xenotropic virus. J Virol. 1977 May;22(2):361–372. doi: 10.1128/jvi.22.2.361-372.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiss R. A., Mason W. S., Vogt P. K. Genetic recombinants and heterozygotes derived from endogenous and exogenous avian RNA tumor viruses. Virology. 1973 Apr;52(2):535–552. doi: 10.1016/0042-6822(73)90349-8. [DOI] [PubMed] [Google Scholar]
- Wong P. K., Russ L. J., McCarter J. A. Rapid, selective procedure for isolation of spontaneous temperature-sensitive mutants of Moloney leukemia virus. Virology. 1973 Feb;51(2):424–431. doi: 10.1016/0042-6822(73)90441-8. [DOI] [PubMed] [Google Scholar]
- Zarling D. A., Temin H. M. High spontaneous mutation rate of an avian sarcoma virus. J Virol. 1975 Jan;17(1):74–84. doi: 10.1128/jvi.17.1.74-84.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]