Generation of a tumorigenic milk-borne mouse mammary tumor virus by recombination between endogenous and exogenous viruses

J Virol. 1997 May;71(5):3895-903. doi: 10.1128/JVI.71.5.3895-3903.1997.

Abstract

Two novel exogenous mouse mammary tumor viruses (MMTV), BALB2 and BALB14, that encode superantigens (Sags) with Vbeta2+ and Vbeta14+ specificities, respectively, were found in the BALB/cT mouse strain. BALB/cT females were crossed with AKR/J males to generate F1 females. Foster nursing of BALB/cT mice on (BALB/cT x AKR/J)F1 mothers resulted in the generation of a new mouse strain, BALB/cLA, that had acquired a new exogenous MMTV (hereafter called LA) with a Vbeta6+/Vbeta8.1+-T-cell-specific Sag. Sequence analysis of the long terminal repeats of the BALB2, BALB14, and LA viruses indicated that LA virus resulted from recombination between BALB14 and the endogenous Mtv-7 provirus. Mtv-7 is expressed only in lymphoid tissues but not the mammary glands of Mtv-7-containing mouse strains such as AKR. In contrast, LA virus was highly expressed in the mammary gland, although it had the sag-specific region from Mtv-7. The LA virus, as well as different recombinant viruses expressed in the mammary glands of (BALB/cT x AKR/J)F1 mice, acquired a specific DNA sequence from BALB14 virus that is required for the mammary-gland-specific expression of MMTV. Since the Sag encoded by LA virus strongly stimulated cognate T cells in vivo, selection for recombinant virus with the Mtv-7 sag most likely occurred because the increased T-cell proliferation resulted in greater lymphoid and mammary gland cell infection. As a result of the higher virus titer, 80% of BALB/cLA females developed mammary gland tumors, although the incidence was only 40% in BALB/cT mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Female
  • Male
  • Mammary Neoplasms, Experimental / etiology*
  • Mammary Tumor Virus, Mouse / genetics*
  • Mice
  • Mice, Inbred AKR
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Milk / virology*
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Recombination, Genetic*
  • Repetitive Sequences, Nucleic Acid
  • Superantigens / chemistry
  • Superantigens / genetics

Substances

  • Receptors, Antigen, T-Cell, alpha-beta
  • Superantigens

Associated data

  • GENBANK/U71270
  • GENBANK/U71271
  • GENBANK/U71272