Faculty Research 1990 - 1999

Title

B and T cells are required for mouse mammary tumor virus spread within the mammary gland.

Document Type

Article

Publication Date

1998

Keywords

Animal, Antigens, Viral/genetics/immunology, B-Lymphocytes, Female, Gene Amplification/immunology, Mammae/immunology/virology, Mammary Neoplasms, Experimental/genetics/immunology/virology, Mammary Tumor Viruses, Mouse/genetics/immunology/pathogenicity, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Pedigree Retroviridae Infections/genetics/immunology/transmission, Superantigens/genetics/immunology, T-Lymphocytes/immunology/virology, Tumor Virus Infections/genetics/immunology/transmission

JAX Source

J Immunol 1998 Sep 1;161(5):2375-82

Grant

CA65795/CA/NCI, CA52646/CA/NCI

Abstract

Mouse mammary tumor virus (MMTV) is an infectious retrovirus transmitted through milk from mother to newborns. MMTV encodes a superantigen (SAg) whose activity is indispensable for the virus life cycle, since a genetically engineered virus with a mutation in the sag gene neither amplified in cells of the immune system of suckling pups nor infected their mammary glands. When wild-type MMTV was injected directly into the mammary glands of uninfected pubescent mice, their lymphoid as well as mammary gland cells became virus infected. To test whether this infection of lymphoid cells was dependent on SAg activity and required for virus spread within the mammary gland, we performed mammary gland injections of wild-type MMTV(C3H) into two strains of transgenic mice that lacked SAg-cognate, V beta 14+ T cells. Neither the MTV-ORF or LEL strains showed infection of their mammary glands. Moreover, no MMTV infection of their peripheral lymphocytes was detected. Similar experiments with mice lacking B cells (mu-chain knockouts) showed no detectable virus spread in the mammary glands or lymphoid tissues. These data suggest that SAg activity and MMTV-infected lymphocytes are required, not only for initial steps of viral infection, but also for virus spread within the mammary gland. Virus spread at late times in infection determines whether MMTV induces mammary tumors.

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