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. 1989 May;63(5):2370–2373. doi: 10.1128/jvi.63.5.2370-2373.1989

Unmyristylated Moloney murine leukemia virus Pr65gag is excluded from virus assembly and maturation events.

A M Schultz 1, A Rein 1
PMCID: PMC250660  PMID: 2649693

Abstract

The gag precursor polyprotein of Moloney murine leukemia virus (MuLV) is normally modified by myristylation of the N-terminal glycine. Previous work showed that the Pr65gag lacking the myristylation site does not associate with cellular membranes or assemble into virus particles. We now report that it also is not cleaved to the mature gag cleavage products within the cell and that it sediments as a free 65-kilodalton monomer in detergent-free cell extracts containing 0.3 M NaCl. Even when the cells containing the mutant are productively infected with wild-type MuLV, the mutant Pr65gag is not processed into cleavage products and is not incorporated into the virions produced by these cells. Thus, the mutant gag molecules seem unable to participate in the normal processes of self-assembly and maturation. We propose that myristate-mediated membrane association is an essential first step in MuLV assembly. This association may also play a role in budding of MuLV.

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Selected References

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  1. 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]
  2. Bigbee W. L., Vanderlaan M., Fong S. S., Jensen R. H. Monoclonal antibodies specific for the M- and N-forms of human glycophorin A. Mol Immunol. 1983 Dec;20(12):1353–1362. doi: 10.1016/0161-5890(83)90166-9. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Crawford S., Goff S. P. A deletion mutation in the 5' part of the pol gene of Moloney murine leukemia virus blocks proteolytic processing of the gag and pol polyproteins. J Virol. 1985 Mar;53(3):899–907. doi: 10.1128/jvi.53.3.899-907.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Donoghue D. J., Sharp P. A., Weinberg R. A. Comparative study of different isolates of murine sarcoma virus. J Virol. 1979 Dec;32(3):1015–1027. doi: 10.1128/jvi.32.3.1015-1027.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Durbin R. K., Manning J. S. Coordination of cleavage of gag and env gene products of murine leukemia virus: implications regarding the mechanism of processing. Virology. 1984 Apr 30;134(2):368–374. doi: 10.1016/0042-6822(84)90304-0. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Henderson L. E., Krutzsch H. C., Oroszlan S. Myristyl amino-terminal acylation of murine retrovirus proteins: an unusual post-translational proteins modification. Proc Natl Acad Sci U S A. 1983 Jan;80(2):339–343. doi: 10.1073/pnas.80.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Katoh I., Yoshinaka Y., Rein A., Shibuya M., Odaka T., Oroszlan S. Murine leukemia virus maturation: protease region required for conversion from "immature" to "mature" core form and for virus infectivity. Virology. 1985 Sep;145(2):280–292. doi: 10.1016/0042-6822(85)90161-8. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Rein A., McClure M. R., Rice N. R., Luftig R. B., Schultz A. M. Myristylation site in Pr65gag is essential for virus particle formation by Moloney murine leukemia virus. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7246–7250. doi: 10.1073/pnas.83.19.7246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rhee S. S., Hunter E. Myristylation is required for intracellular transport but not for assembly of D-type retrovirus capsids. J Virol. 1987 Apr;61(4):1045–1053. doi: 10.1128/jvi.61.4.1045-1053.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Scheele C. M., Hanafusa H. Proteins of helper-dependent RSV. Virology. 1971 Aug;45(2):401–410. doi: 10.1016/0042-6822(71)90341-2. [DOI] [PubMed] [Google Scholar]
  16. Schultz A. M., Oroszlan S. In vivo modification of retroviral gag gene-encoded polyproteins by myristic acid. J Virol. 1983 May;46(2):355–361. doi: 10.1128/jvi.46.2.355-361.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shields A., Witte W. N., Rothenberg E., Baltimore D. High frequency of aberrant expression of Moloney murine leukemia virus in clonal infections. Cell. 1978 Jul;14(3):601–609. doi: 10.1016/0092-8674(78)90245-3. [DOI] [PubMed] [Google Scholar]
  18. Simons K., Garoff H. The budding mechanisms of enveloped animal viruses. J Gen Virol. 1980 Sep;50(1):1–21. doi: 10.1099/0022-1317-50-1-1. [DOI] [PubMed] [Google Scholar]
  19. Yoshinaka Y., Katoh I., Copeland T. D., Oroszlan S. Murine leukemia virus protease is encoded by the gag-pol gene and is synthesized through suppression of an amber termination codon. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1618–1622. doi: 10.1073/pnas.82.6.1618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Yoshinaka Y., Luftig R. B. Murine leukemia virus morphogenesis: cleavage of P70 in vitro can be accompanied by a shift from a concentrically coiled internal strand ("immature") to a collapsed ("mature") form of the virus core. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3446–3450. doi: 10.1073/pnas.74.8.3446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yoshinaka Y., Luftig R. B. p65 of Gazdar murine sarcoma viruses contains antigenic determinants from all four of the murine leukemia virus (MuLV) gag polypeptides (p15, p12, p30, and p10) and can be cleaved in vitro by the MuLV proteolytic activity. Virology. 1982 Apr 30;118(2):380–388. doi: 10.1016/0042-6822(82)90357-9. [DOI] [PubMed] [Google Scholar]

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