4th International AIDS Conference Stockholm, Sweden. — June 12-16, 1988

Int Conf AIDS. 1988 Jun 12-16;4:1 (abstract no. 1001)

Gerald Myers, C.R. Linder, C.S. Tung
Theoretical Division, Los Alamos National Laboratory, Los Alamos

OBJECTIVE: To elucidate structural features of the HIV LTR that are responsible for regulation of viral expression. Homologous and heterologous transactivation of HIV are effected through both highly specific and less specific cis-regulatory sequences in the LTR. We define the tertiary structures of those LTR DNA sequences which are believed to be responsive to regulatory effectors, i.e. proteins, and correlate this molecular information with results of mutational and biochemical studies.

METHODS: DNA curvature and local helical twist are quantitatively measured, employing computer algorithms, across the various HIV LTR sequences and compared to those of all known retroviral and retrotransposon LTR sequences.

RESULTS: Two DNA curvature patterns are uniquely found in all HIV-1 LTR sequences: one is immediately 5' to the positive enhancer region and the other is immediately 5' to the primer binding site. One or the other of these can be found in HIV-2 and lentiviral sequences, but neither curvature is characteristic of other retroviral LTRs analyzed to date. Furthermore, unique DNA helical patterns are discernible in the control region denoted TAR, which is essential for homologous transactivation. HIV sequence comparisons reveal that only base substitutions that conserve these structures appear to be permitted.

CONCLUSION: At least two of the several critical three-dimensional nucleic acid structures for HIV LTR-directed transactivation can be defined.

880612
1001

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