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.
Golovkina
T V
TV
Department of Microbiology/Cancer Center, University of Pennsylvania, Philadelphia 19104-6142, USA.
Dudley
J P
JP
Jaffe
A B
AB
Ross
S R
SR
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D015723:Gene Library; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D018089:Superantigens / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014158:Transcription, Genetic
D000956:Antigens, Viral; D017931:DNA Primers; D018089:Superantigens