Translocations of the chromosomal locus 11q23 that disrupt the MLL gene (alternatively ALL-1 or HRX) are frequently found in children's leukemias. These events fuse the MLL amino terminus in frame with a variety of unrelated proteins. Up to date, 16 di erent fusion partners have been characterized and more are likely to exist. No general unifying property could yet be detected amongst these proteins. We show here that the frequent MLL fusion partner ENL at 19p13.1 interacts with the human homologue of the mouse Abl-Interactor 1 (ABI1) protein. ABI1 in turn, is fused to MLL in the t(10;11)(p11.2;q23) translocation. ABI1 was identi®ed as an ENL binding protein by a yeast two-hybrid screen. The interaction of ENL and ABI1 could be veri®ed in vitro by far-Western blot assays and GST-pulldown studies as well as in vivo by co-immunoprecipitation experiments. A structure-function analysis identi®ed an internal region of ENL and a composite motif of ABI1 including an SH3 domain as mutual binding partners. These data introduce novel aspects that might contribute to the understanding of the process of leukemogenesis by MLL fusion proteins.

The recent identification of coreceptors that mediate efficient entry of human immunodeficiency virus type 1 (HIV-1) suggests new therapeutic and preventive strategies. We analyzed simian immunodeficiency virus (SIV) entry cofactors to investigate whether the macaque SIV model can be used as an experimental model to evaluate these strategies. Similar to primary HIV-1 isolates, a well-characterized molecular clone, SIVmac239, which replicates poorly but efficiently enters into rhesus alveolar macrophages and an envelope variant, SIVmac239/316Env, with an ϳ1,000-fold-higher replicative capacity in macrophages used the ␤-chemokine receptor CCR5 for efficient entry. The transmembrane portion of 316Env allowed low-level entry into cells expressing CCR1, CCR2B, and CCR3. A single amino acid substitution in the V3 loop of SIVmac239/316Env, 321P3S, impaired the ability to enter into the T-B hybrid cell line CEMx174 but had relatively little effect on entry into primary cells and HOS.CD4 cells expressing CCR5. Although CEMx174 cells do not express CCR5, most SIVmac variants entered this hybrid cell line efficiently but did not enter the parental T-cell line CEM. It seems likely that CEMx174 cells express an as-yet-unidentified, perhaps B-cell-derived cofactor which allows efficient entry of SIVmac.

Different rates of disease progression may be associated with different human immunodeficiency virus type 1 (HIV-1) promoter and/or transactivator activities. We therefore analyzed the sequences and activities of the first exon of Tat, tat1, and the promoter/trans-acting responsive (TAR) regions amplified directly from peripheral blood mononuclear cells obtained from five long-term nonprogressors and eight progressing HIV-1-infected individuals. The majority of tat1 alleles and promoter/TAR regions from all patients were intact and showed comparable activities in transient reporter assays. A substantial number of point mutations and some length variations were observed in the promoter/TAR region. In a single nonprogressor, the Sp1 binding site 3 was consistently altered and the transcriptional activity in the presence of Tat was diminished. Some LTR clones from a rapid progressor contained a fourth Sp1 binding site, which was associated with an elevated basal promoter activity. These data suggest that defects in the promoter/TAR region or tat1 are rare and that different promoter/transactivator activities are not commonly associated with different progression rates.