It has also been proposed to act as a tumor suppressor in B-cell malignancy. check details Here, we present a novel in vivo system enabling the targeted genetic manipulation of cells expressing Prdm1, the gene encoding Blimp-1. We created bacterial artificial chromosome-transgenic mice expressing the avian leukosis virus (ALV) receptor TVB, fused to monomeric red fluorescent protein, under regulation by Prdm1 transcriptional elements, and we achieved transduction of TVB-expressing lymphocytes by ALV vectors bearing a subgroup B envelope.

The system presented here incorporates a number of innovations. First, it is the first mammalian transgenic system that employs the ALV receptor Blebbistatin TVB, thus expanding the flexibility and scope of ALV-mediated gene delivery. Second, it represents the first ALV-based system that allows gene transfer and expression into in vivo-activated mature lymphocytes, a cell type that has traditionally presented formidable challenges to efficient retroviral transduction.

Third, Prdm1: TVB-mRFP transgenic animals could provide an invaluable tool for exploring the diverse roles of Blimp-1 in lineage commitment, immune regulation, and tumorigenesis.”
“Binding of the human immunodeficiency virus (HIV) envelope glycoprotein (Env) to the cellular CD4 receptor and a chemokine coreceptor initiates a series of conformational changes in the Env subunits gp120 and gp41. Eventually, the trimeric gp41 folds into a six-helix bundle, thereby inducing fusion of the viral and cellular membranes. C peptides derived from the C-terminal heptad repeat (CHR) of gp41 are efficient entry inhibitors as they block the six-helix bundle formation. Previously, we developed

Amylase a membrane-anchored C peptide (maC46) expressed from a retroviral vector that also shows high activity against virus strains resistant to enfuvirtide (T-20), an antiviral C peptide approved for clinical use. Here, we present a systematic analysis of mutations in Env that confer resistance of HIV type 1 (HIV-1) to maC46. We selected an HIV-1 BaL strain with 10-fold reduced sensitivity to maC46 (BaL_C46) by passaging virus for nearly 200 days in the presence of gradually increasing concentrations of maC46. In comparison to wild-type BaL, BaL_C46 had five mutations at highly conserved positions in Env, three in gp120, one in the N-terminal heptad-repeat (NHR), and one in the CHR of gp41. No mutations were found in the NHR domain around the GIV motif that are known to cause resistance to enfuvirtide. Instead, maC46 resistance was found to depend on complementary mutations in the NHR and CHR that considerably favor binding of the mutated NHR to the mutated CHR over binding to maC46. In addition, resistance was highly dependent on mutations in gp120 that accelerated entry.