Variants with reduced virulence derived from Leishmania major after mutagen treatment |
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Authors: | M MARCHAND S DAOUD R G TITUS J LOUIS T BOON |
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Institution: | International Institute of Cellular and Molecular Pathology, 75 Avenue Hippocrate, B-1200 Brussels, Belgium;World Health Organization Immunology Research and Training Centre, Institute of Biochemistry, University of Lausanne, Switzerland |
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Abstract: | After several in vitro treatments of a virulent population of Leishmania major with the mutagen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), five clones (vir-) were obtained that did not produce cutaneous lesions after subcutaneous injection of 10(6) promastigotes. All the control clones (vir+) obtained from the non-mutagenized parasite population produced progressive cutaneous lesions with as few as 10(3) parasites. Late lesions were observed occasionally after injection of 10(7) vir- parasites. These late lesions appeared to result from the selection of virulent revertants, since parasites isolated from these lesions produced progressive lesions in BALB/c mice almost as readily as the control parasites. Two vir- clones, one vir+ clone and one revertant clone were examined for survival in BALB/c macrophages in vitro. All clones were taken up by the macrophages and transformed into amastigotes. However, vir- clones failed to multiply inside the macrophages. A vir- clone was found to protect mice against a subsequent challenge with vir+ parasites. |
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Keywords: | Leishmania major mutagen variant |
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