EFFECT OF PROTEASE EXPRESSION IN TRANSGENIC MODELS
Although it is well known that small animals such as mice are not optimal models for the study of AIDS pathogenesis, transgenic mice that harbor defective viral genomes that contain a PR sequence or single PR gene have been developed.1-4 The main pathological effect of these transgenic mice is cytotoxicity in tissues in which PR is expressed; for example, targeted ocular expression of PR results in lens fiber cell damage, which causes cataracts.
In particular, the expression of HIV-1 protease driven by an A-crystallin promoter causes proteolysis of the aquaporin protein MIP26 and the lens crystallin proteins, resulting in cataracts. However, the proteolysis patterns of lens proteins in HIV-1 PR transgenic mice suggest that these proteins are not directly processed by HIV-1 PR5; rather, HIV-1 PR activates an endogenous protease, probably calpain, that cleaves the proteins of the lens in HIV-1 PR transgenic mice.4,6 In particular, these studies demonstrate conclusively that HIV PR is active within mammalian cells, that the principal effect of PR expression is cell loss, that the degree of cell loss varies discretely with levels of PR expression,5 and that PR selectively targets host cell proteins.6
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- APOPTOSIS IN ANIMAL MODELS OF HIV-1 DISEASE
- OTHER FORMS OF CELL DEATH: NECROSIS AND AUTOPHAGY
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