The Duplan strain of Radiation Leukemia Virus (RadLV) induces an AIDS-like syndrome when injected intraperitoneally into adult C57BL/6 mice. The mice develop T cell depletion, polyclonal B cell proliferation (lymphadenopathy, splenomegaly), hypergammaglobulinemia, and immune deficiency. This syndrome has recently been designated MAIDS (murine acquired immunodeficiency syndrome). This virus preparation, passaged in vivo, is crude and known to contain different strains of retroviruses. To identify the etiologic agent of this disease, we first infected fibroblasts in vitro with this crude virus mixture. Supernatants of these cultures induced disease. Unintegrated viral DNA from fibroblasts newly-infected with this virus preparation was extracted by the Hirt supernatant method and analysed with various viral probes: 8.8 and 4.8 kb DNA species were detected and molecularly cloned in pUC 18 (clones Du9S and Du5H, respectively). An unique DNA sequence derived from the gag region of the defective Du5H genome did not hybridize to various other retroviral DNA's (Moloney MuLV, N-Cl-35 or Du9S). The restriction of Du9S is similar to the map of other RadLV's. The defective Du5H DNA was transfected into fibroblasts in the presence of the neomycin resistance gene and rescued with the non-leukemogenic ecotropic RadLV (G6T2). This virus complex, as well as the ecotropic virus alone, were inoculated into C57BL/6 mice to test their pathogenic potential. The rescued cloned defective virus caused MAIDS, whereas the helper virus (G6T2) alone did not cause disease. Sequence data shows that the defective virus has large deletions in pol and env, and that the gag region is conserved and harbors a novel p12 sequence. This mouse model may help in understanding some important mechanisms underlying the biology of retrovirus-induced immunodeficiency syndromes, such as AIDS.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.74558 |
| Date | January 1990 |
| Creators | Aziz, Douglas C. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001167905, proquestno: AAINN66458, Theses scanned by UMI/ProQuest. |
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