retroviruses, including Moloney MuLV. is the U3 enhancer region (DesGroselllers 
et al.. 1983: Chatis et al.. 1983). Other regions including the env region 
also appear to increase the virulence of the U3 region but do not by themselves 
confer tropism. Studies where the U3 region of Friend MuLV was substituted 
with the U3 region from Moloney MuLV changed the tropism of the Friend MuLV so 
that it now produced T cell lymphomas Instead of the expected erythroleukemla 
(Chatis et al.. 1983: Chatis et al.. 1984: LI et al.. 1987). 
While not proven, there is evidence to suggest that oncogenic potential of 
a retrovirus may be related to the level of viral expression within the target 
cell (DesGroselllers et al.. 1983: Celander and Haseltlne. 1984: Cullen et al.. 
1985: Weber and Schaffner. 1985)). The ability of a retrovirus to establish 
vlremla within a host Is not related to its ability to cause leukemia. Davis 
et al . (1985) constructed two vectors. One was wild type Moloney MuLV with a 
polyoma virus enhancer Inserted next to the Moloney U3 enhancer. The other 
construct contained the polyoma enhancer, but the Moloney U3 enhancer region 
was deleted. The ability of these vectors to establish vlremla and produce T 
cell lymphomas was compared to wild type Moloney MuLV. All three were capable 
of replicating In tissue culture and produced a continued vlremla In the 
animal, yet only the Intact Mo-MuLV was capable of producing leukemia. It Is 
not known what cells were producing the virus and If they were at risk for 
malignant transformation. These findings suggest that malignant transformation 
by slowly transforming retroviruses requires more than a continued vlremia. 
Properties within the U3 region appear to Increase the malignant potential of 
Moloney MuLV for T cells, and T cell specific protein kinases are activated by 
Insertlonal mutagenesis in some but not all T cell lymphomas. These findings 
raise the question: Does expression correlate with malignant potential? 
Specifically, can a vector be made that will be able to express ADA In T cells 
Recombinant DNA Research, Volume 12 
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