Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Murine leukemia virus infection in immunocompetent adult mice.
Diss Abstr Int [B]; 55(5):1795 1994. Unique Identifier : AIDSLINE ICDB/95607692 Tumas KM; Univ. of Pennsylvania
Abstract:
Murine leukemia viruses (MuLVs) are retroviruses which induce several types of hemopoietic diseases in susceptible mice. To investigate leukemia development in immunocompetent adult mice, we have utilized the MuLV, E-55(+), which induces a T cell lymphoma/leukemia in adult BALB.K mice after a latency period of approximately 6 months. The distribution of integrated provirus during E-55(+) infection of adult, immunocompetent BALB.K mice can be separated into three phases. In the acute phase (1-2 weeks post virus inoculation), high levels of integrated provirus can be detected in the bone marrow but not in the thymus. Bone marrow colony assays demonstrated that a target for the E-55(+) virus in the bone marrow was a early progenitor cell capable of differentiating into many hemopoietic lineages. Further evidence that an early progenitor cell is a target of the E-55(+) virus was provided by adoptive transfer experiments in which virus infected bone marrow injected into lethally irradiated BALB.K mice resulted in null cell, T cell and myeloid leukemias. During the second phase, 8-14 weeks post infection, integrated provirus is undetectable in any tissue. This phase is unique to immunocompetent mice because in immunosuppressed mice levels of integrated provirus increases steadily during this time suggesting that the immune response of the immunocompetent host is responsible for keeping the virus at undetectable levels. Most mice have detectable integrated provirus and show signs of leukemia (large palpable spleens) by the last phase, 14 weeks post infection. Virus isolated from E-55(+) virus-induced leukemic BALB.K mice have lost the monoclonal antibody 55 epitope found on E-55(+) infected cells and can not be neutralized by antisera from E-55(+) infected BALB.K mice. Sequence analysis of the env gene showed that these newly emerging E-55(-) like viruses are generated as the result of a recombination between the exogenous E-55(+) virus and the endogenous, ecotropic emv-1 virus carried within the BALB.K genome. The E-55(-) like viruses, which escape the E-55(+) virus-induced immune response, can induce leukemia despite the presence of naturally occurring antibodies which recognize the E-55(-) virus. Thus, virus induced leukemia in immunocompetent mice requires evasion of both the preexisting and the induced immune responses. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD94-27630)
Keywords: Animal Gene Products, env/IMMUNOLOGY Immunocompetence Leukemia Viruses, Murine/*IMMUNOLOGY Mice Proviruses/IMMUNOLOGY Retroviridae Infections/*IMMUNOLOGY THESIS 950830
M9581000
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Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
