Human immunodeficiency virus (HIV) encephalitis (HIVE), the most severe neurological complication associated with HIV-1 infection, leads to the onset of HIV-1-associated dementia (HAD). Several HIV-1 viral proteins have been implicated in HIVE-associated neurodegeneration. HIV-1 viral protein R (Vpr), a virion associated gene product known to induce apoptosis in nonproliferating cells, including neurons, is thought to contribute to the neuropathogenesis associated with HIVE. Though current research suggests that Vpr plays a significant role in neuropathogenesis, the presence of Vpr in the brain tissue of HIVE patients has not been assessed. Using a panel of HIVE patient brain tissue, the authors have shown that Vpr is present in detectable amounts in both the basal ganglia and frontal cortex of all HIVE brain tissue samples tested. Double immunofluorescence indicated that Vpr was found in the macrophages and neurons, but not in the astrocytes, of HIVE patients. These results for the first time show the presence of Vpr in vivo and further support the role of Vpr in neuropathogenesis.

Multiple ankyrin repeat motif‐containing proteins play an important role in protein–protein interactions. ANKHD1 proteins are known to possess multiple ankyrin repeat domains and a single KH domain with no known function. Using yeast two‐hybrid system analysis, we identified a novel splice variant of ANKHD1. This splice variant of ANKHD1, which we designated as HIV‐1 Vpr‐binding ankyrin repeat protein (VBARP), does not contain the signature KH domain, and codes for only a single ankyrin repeat motif. We characterized VBARP by molecular and functional analysis, revealing that VBARP is ubiquitously expressed in different tissues as well as cell lines of different lineage. In addition, blast searches indicated that orthologs and homologs to VBARP exist in different phyla, suggesting that VBARP might be evolutionarily conserved, and thus may be involved in basic cellular function(s). Furthermore, biochemical analysis revealed the presence of two VBARP isoforms coding for 69 and 49 kDa polypeptides, respectively, that are primarily localized in the cytoplasm. Functional analysis using short interfering RNA approaches indicate that this gene product is essential for cell survival through its regulation of caspases. Taken together, these results indicate that VBARP is a novel splice variant of ANKHD1 and may play a role in cellular apoptosis (antiapoptotic) and cell survival pathway(s).