Cellular protein TDP-43 and regulation of HIV-1 gene expression

摘要

Compositions including a polypeptide or nucleic acid sequence encoding a polypeptide that binds TAR DNA (particularly the region -18 to +28 of HIV-LTR DNA) and that does not bind to TAR RNA (particularly the region + 1 to +80 of the TAR RNA) are disclosed. The cellular binding protein TDP- 43 including the polypeptide has an estimated molecular weight of between about 40 kD and 46 kD as determined by SDS polyacrylamide gel electrophoresis. Fusion proteins that include the entire cellular binding protein TDP-43 or fragments thereof are also described. The cellular binding protein, peptide fragments and nucleic acid sequences encoding them, repress HIV gene expression. Methods for preparing the cellular binding protein from cells as recombinant proteins with recombinant host cells are also disclosed. Antibodies to the TDP-43 cellular binding protein are also described. The isolated nucleic acid sequences of the protein and its fragments are described in the construction of retroviral vectors. Methods for using the cellular binding protein, polypeptides thereof, and nucleic acid sequences encoding the protein and its fragments in the preparation of pharmaceutical preparations and in methods for repressing HIV gene expression are also disclosed.