Methods of treating intestinal diseases and inflammatory...

A - Human Necessities – 61 – K

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A61K 31/502 (2006.01) A61P 1/00 (2006.01) A61P 27/06 (2006.01) A61P 31/18 (2006.01)

Patent

CA 2752674

Of the cytopathic retroviruses that affect mammals, including HIV-I, many selectively infect CD4+ T cells and cause immunosuppressive syndromes. These diseases destroy both the thymus and the small and large intestines, after infecting and killing T-lineage cells in both tissues. A mutant of the murine leukemia retrovirus MoMuL V -TB, called ts1, causes this syndrome in susceptible strains of mice. In FVB/N strain mice that are infected at birth, thymic atrophy, CD4+ T cell loss, intestinal collapse, body wasting, and death occur by 30-40 days postinfection (dpi). Apoptosis of ts1 -infected T-lineage cells, in the thymus, peripheral lymphoid system and intestines is caused by accumulation of the ts1 mutant viral envelope preprotein gPr80env which is inefficiently cleaved into the mature viral proteins gp70 and PrP 15E.

Parmi les rétrovirus cytopathogènes affectant les mammifères, dont le VIH-I, beaucoup infectent de façon sélective les lymphocytes T CD4+ et sont à l'origine d'un syndrome immunosuppresseur. Ces maladies détruisent à la fois le thymus et le gros intestin et l'intestin grêle, après avoir infecté et tué les cellules de lignée lymphocytaire T dans lesdits tissus. Un mutant du rétrovirus de la leucémie murine, MoMuL V -TB, connu sous le nom de ts1, provoque ce syndrome chez des souches de souris sensibles. Chez les souris de souche FVB/N, infectées à la naissance, une atrophie du thymus, une perte de lymphocytes T CD4+, un collapsus intestinal, une dénutrition et, finalement, la mort interviennent dans les 30 à 40 jours suivant l'infection. L'apoptose des cellules de lignée lymphocytaire T infectées par ts1, dans le thymus, le système lymphoïde périphérique et les intestins, est provoquée par l'accumulation de pré-protéine virale d'enveloppe mutante de ts1, gPr80env, qui est inefficacement clivée pour donner les protéines virales matures gp70 et PrP 15E.

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