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Recombinants of amphotropic murine leukemia virus (A-MuLV) have found widespread use in retroviral vector systems due to their ability to efficiently and stably infect cells of several different species, including human. Previous work has shown that replication-competent recombinants containing the amphotropic env gene, encoding the major SU envelope glycoprotein that determines host tropism, induce lymphomas in vivo. We show here that these viruses also induce a spongiform encephalomyelopathy in mice inoculated perinatally. This fatal central nervous system disease is characterized by noninflammatory spongiform lesions of nerve and glial cells and their processes, and is associated with moderate astro- and microgliosis. The first clinical symptoms are ataxia, tremor, and spasticity, progressing to complete tetraparesis and incontinence, and finally death of the animal. Sequences within the amphotropic env gene are necessary for disease induction. Coinfection of A-MuLV recombinants with nonneuropathogenic ecotropic or polytropic MuLV drastically increases the incidence, degree, and distribution of the neurodegenerative disorder. The consequence of these results in view of the use of A-MuLV recombinants in the clinic is discussed.

Interferon consensus sequence binding protein (ICSBP)-mutant mice were analyzed to determine the role of ICSBP in the antiviral responses of the immune system and chronic myelogenous leukemia (CML). ICSBP mutants exhibited normal antiviral responses to vesicular stomatitis virus indicating that the interferon, B and T lymphocytic system was not altered by ICSBP- deficiency. However, the mutant mice died after being infected with the lymphocytic choriomeningitis virus. Furthermore, the mutants exhibited hematologic neoplasia that is characteristic of CML.

Beta7-regulated adhesive associations between lymphocytes and endothelial cells determine the gut-associated lymphoid tissue formation. In mice deficient for the beta7 integrin subfamily of adhesion molecules (alpha4beta7 and alphaEbeta7), the development of lymphocytes remains normal. However, the number of intra-epithelial lymphocytes of the intestine (IELs) decreases in these mice. This occurs because alpha4beta7 regulates prothymocyte migration from bone marrow to thymus, and alphaEbeta7 immobilizes a number of IELs.

Randomly generated immune responses activated by enteric antigens result in bowel infection in mice mutants which lack Interleukin-10 (IL-10) activity. IL-10 affects immunoregulation in the intestinal tract, and influences the growth and cell differentiation of immune system cell populations. Chronic enterocolitis in IL-10 deficient mutants affects the duodenum, the adjacent jejunum and colon. IL-10 is thus experimentally demonstrated to regulate intestinal immuno-responses.

Reports that the formation of the gut-associated lymphoid tissue (GALT) is severely impaired in mice deficient for the beta7 integrin subfamily adhesion molecules. GALT as a major compartment of the immune system; Parts of the GALT, including Peyer's patches and lamina propria lymphoctyes.