Novel leukaemogenic retroviruses isolated from cell line derived from spontaneous AKR tumour

Finn Skou Pedersen, Robert L. Crowther, Donald Y. Tenney, Andreas M. Reimold, William A. Haseltine

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Viruses isolated from leukaemic and preleukaemic tissues of the AKR mouse differ in their ability to induce thymic lymphomas. The Gross passage A virus, which originates from the thymus of a leukaemic AKR mouse1, and the MCF viruses, isolated from preleukaemic and leukaemic AKR tissues2,3, accelerate the onset of disease on injection into newborn AKR mice 3,4 whereas the endogenous ecotropic Akv virus, which is expressed in AKR mice from mid-gestation onward, is nonleukaemogenic3,5,6. What are the structural features of the genome that account for the leukaemogenic activity of these viruses? The observation that the gp70 envelope glycoprotein of the leukaemogenic MCF virus contain ecotropic and xenotropic regions 7-9 raised the possibility that the structure of the gp70 gene was the major determinant of leukaemogenic activity2. However, a cloned, in vitro passaged, leukaemogenic isolate of the Gross A virus very closely resembles that of the nonleukaemogenic Akv virus in the gag-pol and gp70 coding regions of the genome10. Most of the differences in structure of the Gross A and Akv viruses are located within the 3′-terminal 1,000 nucleotides - this raises the possibility that sequences outside the gp70 gene which are proximal to the 3′ end of the genome encode determinants of leukaemogenic activity. Due to the complex passage history of the Gross A virus we sought to isolate further leukaemogenic AKR viruses that had not been passaged in other animals to determine whether or not they resembled the Gross A virus. Here we report the isolation and characterization of new leukaemogenic viruses from a lymphoid cell line derived from a spontaneous AKR tumour. These isolates resemble the Gross A virus in the 3′ region of the genome. Our results suggest that this region encodes determinants of leukaemogenic potency and that major changes in the envelope glycoprotein are not necessary for the leukaemogenic activity of these viruses.

Original languageEnglish (US)
Pages (from-to)167-170
Number of pages4
JournalNature
Volume292
Issue number5819
DOIs
StatePublished - 1981

ASJC Scopus subject areas

  • General

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