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. 1997 Nov;71(11):8923–8927. doi: 10.1128/jvi.71.11.8923-8927.1997

A small region of the ecotropic murine leukemia virus (MuLV) gag gene profoundly influences the types of polytropic MuLVs generated in mice.

M Lavignon 1, J Richardson 1, L H Evans 1
PMCID: PMC192366  PMID: 9343260

Abstract

The vast majority of recombinant polytropic murine leukemia viruses (MuLVs) generated in mice after infection by ecotropic MuLVs can be classified into two major antigenic groups based on their reactivities to two monoclonal antibodies (MAbs) termed Hy 7 and 516. These groups very likely correspond to viruses formed by recombination of the ecotropic MuLV with two distinct sets of polytropic env genes present in the genomes of inbred mouse strains. We have found that nearly all polytropic MuLVs identified in mice infected with a substrain of Friend MuLV (F-MuLV57) are reactive with Hy 7, whereas mice infected with Moloney MuLV (Mo-MuLV) generate major populations of both Hy 7- and 516-reactive polytropic MuLVs. We examined polytropic MuLVs generated in NFS/N mice after inoculation with Mo-MuLV-F-MuLV57 chimeras to determine which regions of the viral genome influence this difference between the two ecotropic MuLVs. These studies identified a region of the MuLV genome which encodes the nucleocapsid protein and a portion of the viral protease as the only region that influenced the difference in polytropic-MuLV generation by Mo-MuLV and F-MuLV57.

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Selected References

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  1. Adachi A., Sakai K., Kitamura N., Nakanishi S., Niwa O., Matsuyama M., Ishimoto A. Characterization of the env gene and long terminal repeat of molecularly cloned Friend mink cell focus-inducing virus DNA. J Virol. 1984 Jun;50(3):813–821. doi: 10.1128/jvi.50.3.813-821.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Battini J. L., Heard J. M., Danos O. Receptor choice determinants in the envelope glycoproteins of amphotropic, xenotropic, and polytropic murine leukemia viruses. J Virol. 1992 Mar;66(3):1468–1475. doi: 10.1128/jvi.66.3.1468-1475.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bosselman R. A., Van Griensven L. J., Vogt M., Verma I. M. Genome organization of retroviruses. VI. Heteroduplex analysis of ecotropic and xenotropic sequences of moloney mink cell focus-inducing viral RNA obtained from either a cloned isolate or a thymoma cell line. J Virol. 1979 Dec;32(3):968–978. doi: 10.1128/jvi.32.3.968-978.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chatis P. A., Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408–4411. doi: 10.1073/pnas.80.14.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chattopadhyay S. K., Cloyd M. W., Linemeyer D. L., Lander M. R., Rands E., Lowy D. R. Cellular origin and role of mink cell focus-forming viruses in murine thymic lymphomas. Nature. 1982 Jan 7;295(5844):25–31. doi: 10.1038/295025a0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Chesebro B., Britt W., Evans L., Wehrly K., Nishio J., Cloyd M. Characterization of monoclonal antibodies reactive with murine leukemia viruses: use in analysis of strains of friend MCF and Friend ecotropic murine leukemia virus. Virology. 1983 May;127(1):134–148. doi: 10.1016/0042-6822(83)90378-1. [DOI] [PubMed] [Google Scholar]
  8. Chesebro B., Portis J. L., Wehrly K., Nishio J. Effect of murine host genotype on MCF virus expression, latency, and leukemia cell type of leukemias induced by Friend murine leukemia helper virus. Virology. 1983 Jul 15;128(1):221–233. doi: 10.1016/0042-6822(83)90332-x. [DOI] [PubMed] [Google Scholar]
  9. Chien Y. H., Verma I. M., Shih T. Y., Scolnick E. M., Davidson N. Heteroduplex analysis of the sequence relations between the RNAs of mink cell focus-inducing and murine leukemia viruses. J Virol. 1978 Oct;28(1):352–360. doi: 10.1128/jvi.28.1.352-360.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cloyd M. W., Chesebro B., Portis J. L., Weir M. MCF-specific murine monoclonal antibodies made against AKR-247 MCF virus recognize a unique determinant associated with the gp70-p-15(E) complex. J Virol. 1982 Mar;41(3):1112–1117. doi: 10.1128/jvi.41.3.1112-1117.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Donoghue D. J., Rothenberg E., Hopkins N., Baltimore D., Sharp P. A. Heteroduplex analysis of the nonhomology region between Moloney MuLV and the dual host range derivative HIX virus. Cell. 1978 Aug;14(4):959–970. doi: 10.1016/0092-8674(78)90350-1. [DOI] [PubMed] [Google Scholar]
  12. Elder J. H., Gautsch J. W., Jensen F. C., Lerner R. A., Hartley J. W., Rowe W. P. Biochemical evidence that MCF murine leukemia viruses are envelope (env) gene recombinants. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4676–4680. doi: 10.1073/pnas.74.10.4676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Evans L. H., Cloyd M. W. Friend and Moloney murine leukemia viruses specifically recombine with different endogenous retroviral sequences to generate mink cell focus-forming viruses. Proc Natl Acad Sci U S A. 1985 Jan;82(2):459–463. doi: 10.1073/pnas.82.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Evans L. H., Cloyd M. W. Generation of mink cell focus-forming viruses by Friend murine leukemia virus: recombination with specific endogenous proviral sequences. J Virol. 1984 Mar;49(3):772–781. doi: 10.1128/jvi.49.3.772-781.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Evans L. H., Morrey J. D. Tissue-specific replication of Friend and Moloney murine leukemia viruses in infected mice. J Virol. 1987 May;61(5):1350–1357. doi: 10.1128/jvi.61.5.1350-1357.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Evans L., Nunn M., Duesberg P. H., Troxler D., Scolnick E. RNAs of defective and nondefective components of Friend anemia and polycythemia virus strains identified and compared. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):823–835. doi: 10.1101/sqb.1980.044.01.087. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Gorelick R. J., Henderson L. E., Hanser J. P., Rein A. Point mutants of Moloney murine leukemia virus that fail to package viral RNA: evidence for specific RNA recognition by a "zinc finger-like" protein sequence. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8420–8424. doi: 10.1073/pnas.85.22.8420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Green N., Hiai H., Elder J. H., Schwartz R. S., Khiroya R. H., Thomas C. Y., Tsichlis P. N., Coffin J. M. Expression of leukemogenic recombinant viruses associated with a recessive gene in HRS/J mice. J Exp Med. 1980 Aug 1;152(2):249–264. doi: 10.1084/jem.152.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Housset V., De Rocquigny H., Roques B. P., Darlix J. L. Basic amino acids flanking the zinc finger of Moloney murine leukemia virus nucleocapsid protein NCp10 are critical for virus infectivity. J Virol. 1993 May;67(5):2537–2545. doi: 10.1128/jvi.67.5.2537-2545.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lavignon M., Evans L. A multistep process of leukemogenesis in Moloney murine leukemia virus-infected mice that is modulated by retroviral pseudotyping and interference. J Virol. 1996 Jun;70(6):3852–3862. doi: 10.1128/jvi.70.6.3852-3862.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lavignon M., Walker J. L., Perryman S. M., Malik F. G., Khan A. S., Theodore T. S., Evans L. H. Characterization of epitopes defining two major subclasses of polytropic murine leukemia viruses (MuLVs) which are differentially expressed in mice infected with different ecotropic MuLVs. J Virol. 1994 Aug;68(8):5194–5203. doi: 10.1128/jvi.68.8.5194-5203.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mann R., Mulligan R. C., Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell. 1983 May;33(1):153–159. doi: 10.1016/0092-8674(83)90344-6. [DOI] [PubMed] [Google Scholar]
  25. Menéndez-Arias L., Weber I. T., Oroszlan S. Mutational analysis of the substrate binding pocket of murine leukemia virus protease and comparison with human immunodeficiency virus proteases. J Biol Chem. 1995 Dec 8;270(49):29162–29168. doi: 10.1074/jbc.270.49.29162. [DOI] [PubMed] [Google Scholar]
  26. Méric C., Goff S. P. Characterization of Moloney murine leukemia virus mutants with single-amino-acid substitutions in the Cys-His box of the nucleocapsid protein. J Virol. 1989 Apr;63(4):1558–1568. doi: 10.1128/jvi.63.4.1558-1568.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. O'Donnell P. V., Stockert E., Obata Y., Old L. J. Leukemogenic properties of AKR dualtropic (MCF) viruses: amplification of murine leukemia virus-related antigens on thymocytes and acceleration of leukemia development in AKR mice. Virology. 1981 Jul 30;112(2):548–563. doi: 10.1016/0042-6822(81)90301-9. [DOI] [PubMed] [Google Scholar]
  28. Oliff A. I., Hager G. L., Chang E. H., Scolnick E. M., Chan H. W., Lowy D. R. Transfection of molecularly cloned Friend murine leukemia virus DNA yields a highly leukemogenic helper-independent type C virus. J Virol. 1980 Jan;33(1):475–486. doi: 10.1128/jvi.33.1.475-486.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Oroszlan S., Luftig R. B. Retroviral proteinases. Curr Top Microbiol Immunol. 1990;157:153–185. doi: 10.1007/978-3-642-75218-6_6. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Perryman S., Nishio J., Chesebro B. Complete nucleotide sequence of Friend murine leukemia virus, strain FB29. Nucleic Acids Res. 1991 Dec 25;19(24):6950–6950. doi: 10.1093/nar/19.24.6950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Prats A. C., Housset V., de Billy G., Cornille F., Prats H., Roques B., Darlix J. L. Viral RNA annealing activities of the nucleocapsid protein of Moloney murine leukemia virus are zinc independent. Nucleic Acids Res. 1991 Jul 11;19(13):3533–3541. doi: 10.1093/nar/19.13.3533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Prats A. C., Roy C., Wang P. A., Erard M., Housset V., Gabus C., Paoletti C., Darlix J. L. cis elements and trans-acting factors involved in dimer formation of murine leukemia virus RNA. J Virol. 1990 Feb;64(2):774–783. doi: 10.1128/jvi.64.2.774-783.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Prats A. C., Sarih L., Gabus C., Litvak S., Keith G., Darlix J. L. Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA. EMBO J. 1988 Jun;7(6):1777–1783. doi: 10.1002/j.1460-2075.1988.tb03008.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rein A., Harvin D. P., Mirro J., Ernst S. M., Gorelick R. J. Evidence that a central domain of nucleocapsid protein is required for RNA packaging in murine leukemia virus. J Virol. 1994 Sep;68(9):6124–6129. doi: 10.1128/jvi.68.9.6124-6129.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rein A. Interference grouping of murine leukemia viruses: a distinct receptor for the MCF-recombinant viruses in mouse cells. Virology. 1982 Jul 15;120(1):251–257. doi: 10.1016/0042-6822(82)90024-1. [DOI] [PubMed] [Google Scholar]
  37. Richardson J., Corbin A., Pozo F., Orsoni S., Sitbon M. Sequences responsible for the distinctive hemolytic potentials of Friend and Moloney murine leukemia viruses are dispersed but confined to the psi-gag-PR region. J Virol. 1993 Sep;67(9):5478–5486. doi: 10.1128/jvi.67.9.5478-5486.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rommelaere J., Faller D. V., Hopkins N. Characterization and mapping of RNase T1-resistant oligonucleotides derived from the genomes of Akv and MCF murine leukemia viruses. Proc Natl Acad Sci U S A. 1978 Jan;75(1):495–499. doi: 10.1073/pnas.75.1.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schultz A., Rein A. Maturation of murine leukemia virus env proteins in the absence of other viral proteins. Virology. 1985 Sep;145(2):335–339. doi: 10.1016/0042-6822(85)90168-0. [DOI] [PubMed] [Google Scholar]
  40. Shih T. Y., Weeks M. O., Troxler D. H., Coffin J. M., Scolnick E. M. Mapping host range-specific oligonucleotides within genomes of the ecotropic and mink cell focus-inducing strains of Moloney murine leukemia virus. J Virol. 1978 Apr;26(1):71–83. doi: 10.1128/jvi.26.1.71-83.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
  42. Shoemaker C., Goff S., Gilboa E., Paskind M., Mitra S. W., Baltimore D. Structure of a cloned circular Moloney murine leukemia virus DNA molecule containing an inverted segment: implications for retrovirus integration. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3932–3936. doi: 10.1073/pnas.77.7.3932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sitbon M., Nishio J., Wehrly K., Lodmell D., Chesebro B. Use of a focal immunofluorescence assay on live cells for quantitation of retroviruses: distinction of host range classes in virus mixtures and biological cloning of dual-tropic murine leukemia viruses. Virology. 1985 Feb;141(1):110–118. doi: 10.1016/0042-6822(85)90187-4. [DOI] [PubMed] [Google Scholar]
  44. Yu Q., Darlix J. L. The zinc finger of nucleocapsid protein of Friend murine leukemia virus is critical for proviral DNA synthesis in vivo. J Virol. 1996 Sep;70(9):5791–5798. doi: 10.1128/jvi.70.9.5791-5798.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zhang Y., Barklis E. Nucleocapsid protein effects on the specificity of retrovirus RNA encapsidation. J Virol. 1995 Sep;69(9):5716–5722. doi: 10.1128/jvi.69.9.5716-5722.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

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