2.0 Objectives 
Replication of human retroviruses is dependent upon virally 
encoded transactivator proteins. These proteins often interact 
with host cell factors and specifically modulate host cell 
processes. One approach to the treatment of viral infections is 
to inhibit the function of essential viral genes by expression of 
transdominant forms of viral transactivators which inactivate 
them. The rev gene of HIV represents one such essential viral 
regulatory protein. Specific mutations with the coding sequence 
of Rev render the virus replication defective. We have 
previously shown that a dominant negative form of Rev, M10, 
inhibits productive viral replication but does not appear to 
interfere with normal cellular functions. 
In this proposal, the effects of stable expression of a Rev 
transdominant protein will be assessed in peripheral blood T 
lymphocytes in patients. Expression of this protein conferred 
substantial resistance to HIV infection in stably transduced T 
cells in the laboratory, without affecting induction of HIV 
transcription mediated by either the kB regulatory element or Tat 
within CEM M10 subclones. In EL-4 and Jurkat leukemia lines, 
constitutive expression of M10 did not affect the induction of 
IL-2 secretion by mitogens. We have optimized : the delivery of 
this gene to T lymphoid cells, examined its resistance to 
infection by primary viral isolates, and assessed its effect on T 
cell function. These studies suggest that Rev M10 may provide a 
therapeutic effect in AIDS patients. The emphasis of this 
proposal is to direct expression to peripheral blood lymphocytes 
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Recombinant DNA Research, Volume 18 
