Skip to main content
Log in

Recovery of glycosylatedgag virus from mice infected with a glycosylatedgag-negative mutant of moloney murine leukemia virus

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Two independent pathways forgag gene expression exist in Moloney murine leukemia virus (M-MuLV). One begins with Pr65gag that is processed and cleaved into the internal structural proteins of the virion. The other pathway begins with the glycosylatedgag polyprotein, gPr80gag. gPr80gag consists of Pr65gag plus additional N-terminal residues and it is glycosylated. A glycosylated-gag-negative mutant of M-MuLV (Ab-X-MLV) was previously constructed and shown to replicate in tissue culture. To test for the importance of glycosylatedgag in vivo, the Ab-X-MLV mutant was inoculated intraperitoneally into newborn NIH Swiss mice. Mutant-infected mice developed typical lymphoblastic lymphomas at rates comparable to wild-type M-MuLV at either high (2 × 104 XC pfu/animal) or low (2 × 102 XC pfu/animal) doses. However, when viral protein expression was examined in the resultant tumors, six out of six mice showed evidence of virus that had recovered gPr80gag expression. These results suggest that glycosylatedgag is important for M-MuLV propagation or leukemogenesis in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Brightman BK, Chandy KG, Spencer RH, Gupta S, Pattengale PK, Fan H. Characterization of lymphoid tumors induced by a recombinant murine retrovirus carrying the avian v-myc oncogene: Identification of novel (B-lymphoid) tumors in the thymus. J Immunol 141:2844–2854;1988.

    PubMed  Google Scholar 

  2. Coffin, J. Structure of the retroviral genome. In: Weiss R, Teich N, Varmus H, Coffin J, eds. Molecular Biology of Tumor Viruses: RNA Tumor Viruses. Cold Spring Harbor, Cold Spring Harbor Laboratory, 261–368;1984.

    Google Scholar 

  3. Daniel MD, Kirchhoff F, Czajak SC, Sehgal PK, Desrosiers RC. Protective effects of a live attenuated SIV vaccine with a deletion in thenef gene. Science 258:1938–1941;1992.

    PubMed  Google Scholar 

  4. Danos O, Mulligan RC. Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc Natl Acad Sci USA 85:6460–6464:1988.

    PubMed  Google Scholar 

  5. Dickson C, Eisenman R, Fan H, Hunter E, Teich N. Protein biosynthesis and assembly. In: Weiss R, Teich N, Varmus H, Coffin J, eds. Molecular Biology of Tumor viruses: RNA Tumor Viruses. Cold Spring Harbor, Cold Spring Harbor Laboratory, 513–648;1984.

    Google Scholar 

  6. Edwards SA, Fan H.gag-Related polyproteins of Moloney murine leukemia virus: Evidence for independent synthesis of glycosylated and unglycosylated forms. J Virol 30:551–563;1979.

    PubMed  Google Scholar 

  7. Edwards SA, Fan H. Sequence relationship of glycosylated and unglycosylatedgag polyproteins of Moloney murine leukemia virus. J Virol 35:41–51;1980.

    PubMed  Google Scholar 

  8. Edwards SA, Lin YC, Fan H. Association of murine leukemia virusgag antigen with extracellular matrices in productively infected mouse cells. Virology 116:306–317;1982.

    Article  PubMed  Google Scholar 

  9. Evans LH, Cloyd MW. Friend and Moloney murine leukemia viruses specifically recombine with different endogenous retroviral sequences to generate mink cell focus-forming viruses. Proc Natl Acad Sci USA 82:459–463;1985.

    PubMed  Google Scholar 

  10. Evans LH, Dresler S, Kabat D. Synthesis and glycosylation of polyprotein precursors to the internal core proteins of Friend murine leukemia virus. J Virol 24:865–874;1977.

    PubMed  Google Scholar 

  11. Fan H, Chute H, Chao E, Feuerman M. Construction and characterization of Moloney murine leukemia virus mutants unable to synthesize glycosylatedgag polyprotein. Proc Natl Acad Sci USA 80:5965–5969;1983.

    PubMed  Google Scholar 

  12. Fan H, Jaenisch R, MacIsaac P. Low-multiplicity infection of Moloney murine leukemia virus in mouse cells: Effect on number of viral DNA copies and virus production in producer cells. J Virol 28:802–809;1978.

    PubMed  Google Scholar 

  13. Hanecak R, Pattengale PK, Fan H. Addition of substitution of simian virus 40 enhancer sequences into the Moloney murine leukemia virus (M-MuLV) long terminal repeat yields infectious M-MuLV with altered biological properties. J Virol 62:2427–2436;1988.

    PubMed  Google Scholar 

  14. Ji JP, Loeb LA. Fidelity of HIV-1 reverse transcriptase copying RNA in vitro. Biochemistry 31:954–958;1992.

    Article  PubMed  Google Scholar 

  15. Kestler HW III, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC. Importance of thenef gene for maintenance of high virus loads and for development of AIDS. Cell 65:651–662;1991.

    Article  PubMed  Google Scholar 

  16. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685;1970.

    Article  PubMed  Google Scholar 

  17. Lang SM, Weeger M, Stahl-Hennig C, Coulibaly C, Hunsmann G, Muller J, Muller-Hermelink H, Fuchs D, Wachter H, Daniel MM, Desrosiers RC, Fleckenstein, B. Importance ofvpr for infection of rhesus monkeys with simian immunodeficiency virus. J Virol 67:902–912;1993.

    PubMed  Google Scholar 

  18. Ledbetter JA, Nowinski RC, Eisenman RN. Biosynthesis and metabolism of viral proteins expressed on the surface of murine leukemia virus-infected cells. Virology 91:116–129;1978.

    Article  PubMed  Google Scholar 

  19. Mulligan RC. The basic science of gene therapy. Science 260:926–932;1993.

    PubMed  Google Scholar 

  20. Prats AC, De Billy G, Wang P, Darlix JL. CUG initiation codon used for the synthesis of a cell surface antigen coded by the murine leukemia virus. J Mol Biol 205:363–372;1989.

    PubMed  Google Scholar 

  21. Roberts JD, Preston BD, Johnston LA, Soni A, Loeb LA, Kunkel TA. Fidelity of two retroviral reverse transcriptases during DNA-dependent DNA synthesis in vitro. Mol Cell Biol 9:469–476;1989.

    PubMed  Google Scholar 

  22. Rowe WP, Pugh WE, Hartley JW. Plaque assay techniques for murine leukemia viruses. Virology 42:1136–1139;1970.

    Article  PubMed  Google Scholar 

  23. Saris CJ, van Eenbergen J, Liskamp RM, Bloemers HP. Structure of glycosylated and unglycosylatedgag andgag-pol precursor proteins of Moloney murine leukemia virus. J Virol 46:841–859;1983.

    PubMed  Google Scholar 

  24. Schultz AM, Lockhart SM, Rabin EM, Oroszlan S. Structure of glycosylated and unglycosylatedgag polyproteins of Rauscher murine leukemia virus: Carbohydrate attachment sites. J Virol 38:581–592;1981.

    PubMed  Google Scholar 

  25. Schultz AM, Oroszlan S. Murine leukemia virusgag polyproteins: The peptide chain unique to Pr80 is located at the amino terminus. Virology 91:481–486;1978.

    Article  PubMed  Google Scholar 

  26. Schultz AM, Rabin EH, Oroszlan S. Post-translational modification of Rauscher leukemia virus precursor polyproteins encoded by thegag gene. J Virol 30:255–266;1979.

    PubMed  Google Scholar 

  27. Schwartzberg P, Colicelli J, Goff SP. Deletion mutants of moloney murine leukemia virus which lack glycosylatedgag protein are replication competent. J Virol 46:538–546;1983.

    PubMed  Google Scholar 

  28. Stoye JP, Coffin JM. The four classes of endogenous murine leukemia virus: Structural relationships and potential for recombination. J Virol 61:2659–2669;1987.

    PubMed  Google Scholar 

  29. Takeuchi Y, Nagumo T, Hoshino H. Low fidelity of cell-free DNA synthesis by reverse transcriptase of human immunodeficiency virus. J Virol 62:3900–3902;1988.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chun, R., Fan, H. Recovery of glycosylatedgag virus from mice infected with a glycosylatedgag-negative mutant of moloney murine leukemia virus. J Biomed Sci 1, 218–223 (1994). https://doi.org/10.1007/BF02253305

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02253305

Key Words

Navigation