The goal of these studies is to elucidate the role specific sequences of the LTR of murine retroviruses as determinants of tissue secificity of infection and of pathogenicity. The objectives are: 1. To test the generality of the hypothesis that enhancer sequences in the LTR determine the tissue tropism and pathogenicity of murine retroviruses.
Specific aims of this objective are to construct isogenic LTRs that differ only in the enhancer region. Enhancer elements of thymotropic, erythrotropic and B cell tropic viruses will be exchanged. 2. To determine whether cellular as well as viral enhancer elements incorporated into viral LTR sequences can function as enhancers for virus replication and can confer tissue specificity upon viral replication.
The specific aims i nclude construction of hybrid LTR sequences that contain cellular enhancer sequences. 3. To define the sequences within the U3 region of the LTR of murine viruses that determine tissue specific transcriptional preference.
Specific aims i nclude alterations in the sequence and sequence arrangement within the tandemly duplicated sequences of the U3 portion of the LTR. 4. To determine whether or not tissue specific enhancer functions are dominant, co-dominant, or recessive. Specific hybrid constructions that contain two or more enhancer sequences derived from different viruses will be constructed. These experiments should provide input in viral pathogenesis. They should also yield information important for understanding of gene expression in differentiated tissues.
| Haseltine, W A; Sodroski, J; Rosen, C (1985) The lor gene and pathogenesis of HTLV-I, -II, and -III. Cancer Res 45:4545s-4549s |
