MOUSE MAMMARY-TUMOR VIRUSES WITH FUNCTIONAL SUPERANTIGEN GENES ARE SELECTED DURING IN-VIVO INFECTION

Mouse mammary tumor virus (MMTV) encodes a superantigen that is important for viral infectivity in vivo. To determine whether superantigen function was required for infection by milk-borne MMTV, we created HYB PRO/Cla transgenic mice. These mice produced a full-length, packaged viral RNA with a frameshift mutation that caused premature termination of the superantigen protein. Young HYB PRO/Cla mice showed no deletion of their cognate V(beta)14(+) T cells, although they shed virus in their milk The nontransgenic offspring of the HYB PRO/Cla mice were infected with this virus, since transgene specific viral transcripts were detected in their mammary glands. Surprisingly, these offspring demonstrated the progressive deletion of V(beta)14(+) T cells characteristic of exogenous MMTV(C3H) infection. Sequence analysis demonstrated that these newly acquired viruses had reconstituted superantigen open reading frames resulting from recombination between the HYB PRO/Cla and endogenous Mtv-1 proviral RNAs. Thus, there is selection during the infection process for MMTVs with functional superantigen genes.