Human Retroviral Gene Expression and Cellular Transcription 
We recently defined the transcriptional regula- 
tion and induction of these retroviruses and 
found that their regulation differs. A distinct T 
cell activation pathway — triggering of the CD3 
component of the T cell antigen receptor com- 
plex — stimulates HIV- 2 gene expression but 
does not affect HIV- 1 . The response to T cell re- 
-<:eptor stimulation in HIV- 2 is mediated by an up- 
stream regulatory element, CD3R, which a se- 
quence-specific DNA-binding protein of the ets 
family recognizes. 
In addition, at least three other cis-acting regu- 
latory sequences contribute to HIV- 2 gene ex- 
pression, including /cB, another ets binding site, 
and an associated element. Jurkat T leukemia cell 
lines containing HIV-2 provirus also show in- 
creased viral replication following stimulation of 
the T cell receptor complex, in contrast to HIV-1 . 
These findings suggest that HIV-2 and HIV-1 
differ in their transcriptional regulation and in- 
duction. These studies also raise the possibility 
that different cofactors contribute to the activa- 
tion of AIDS associated with HIV-1 and HIV-2. 
Expression of Cellular and Retroviral 
Vector Genes in Vivo 
Despite recent advances in the understanding 
of eukaryotic gene regulation, a major obstacle to 
the therapeutic management of human disease 
remains the site-specific expression of genes in 
vivo. Using our knowledge of retroviral gene ex- 
pression, we have developed systems that utilize 
viral vectors to express biologically active pro- 
teins in cells and tissues in vivo. We have devised 
methods that allow a recombinant gene to be ex- 
pressed efficiently at a specific site in vivo by 
direct introduction of genetic material at the time 
of catheterization. A recombinant jS-galactosidase 
gene was expressed in a specific arterial segment 
in vivo by direct infection with a retroviral vector 
or by DNA transfection using liposomes. Several 
cell types in the vessel wall have now been trans- 
duced with recombinant genes, including endo- 
thelial and vascular smooth muscle cells. Site- 
specific gene expression can therefore be 
achieved by direct gene transfer in vivo and 
could be applied to the treatment of such human 
diseases as atherosclerosis, cancer, or AIDS. 
These studies have been supported by grants from 
the National Institutes of Health and the Ameri- 
can Heart Association. 
Biologically active proteins are now being in- 
troduced into cells, including disparate histocom- 
patibility antigens, growth factors, growth inhibi- 
tors, or immune system proteins. The goal of this 
research is not only to understand basic mecha- 
nisms of gene regulation, transcriptional activa- 
tion, and viral gene expression, but also to define 
the biological significance of factors that regulate 
gene expression in complex organisms and to de- 
velop novel molecular interventions for human 
disease. 
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