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

Mouse mammary tumor virus (MMTV) encodes a superantigen that is import ant for viral infectivity in vivo. To determine whether superantigen f unction was required for infection by milk-borne MMTV, we created HYB PRO/Cla transgenic mice. These mice produced a full-length, packaged v iral 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 th eir milk The nontransgenic offspring of the HYB PRO/Cla mice were infe cted with this virus, since transgene specific viral transcripts were detected in their mammary glands. Surprisingly, these offspring demons trated 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 read ing frames resulting from recombination between the HYB PRO/Cla and en dogenous Mtv-1 proviral RNAs. Thus, there is selection during the infe ction process for MMTVs with functional superantigen genes.