Voltage-dependent anion channels: Key players in viral infection.

Viruses control the host cell by exploiting its molecular machinery to facilitate viral replication and propagation. Understanding different viral mechanisms and biochemical pathways is crucial for finding promising therapeutic solutions to viral infections. The mitochondrion is a vital organelle targeted by various types of viruses. More specifically, viruses interact with the voltage-dependent anion channel (VDAC), a porin protein found in the outer mitochondrial membrane. VDAC controls metabolite flux, regulates reactive oxygen species production, and promotes mitochondrial-mediated apoptosis by releasing pro-apoptotic proteins. Hence, a common pathogenic strategy used by many viruses seems to exploit natural pathways that VDAC regulates. This review aims to address the inhibition and enhancement roles of VDAC in viral pathogenesis and outlines multiple links and interactions between VDAC and viral proteins as potential antiviral targets.

Association of VDBP rs4701 Variant, but not VDR/RXR-α Over-Expression with Bone Mineral Density in Pediatric Well-Chelated ß-Thalassemia Patients.

BACKGROUND: The reduced rate of bone formation despite the availability of vitamin D has been reported in ß-thalassemia. Genetic factors, together with environmental ones, could be implicated in this condition. Since vitamin D binding protein (VDBP) maintains bioavailability of vitamin D which binds to vitamin D receptor (VDR)-retinoid X receptor alpha (RXRA) heterodimer to exert its molecular actions, we speculated that vitamin D metabolic-axis expression signature and variants could be potential molecular candidates for bone turnover/disease in thalassemia. To this end, this study aims to analyze VDR/RXRA expression signature, and two VDBP variants in a pilot sample of Egyptian ß-thalassemia children in correlation with bone mineral density (BMD). PATIENTS AND METHODS: Forty-four well-chelated ß-thalassemia children and 40 unrelated controls were enrolled. The serum bone chemistry profile was measured. Peripheral blood mononuclear cells (PBMN) VDR/RXRA expression levels were quantified by Real-Time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). VDBP rs7041 and rs4588 variants were identified by Real-Time allelic discrimination assay. All patients were subjected to lumbar-spine Dual-energy X-ray absorptiometry (DEXA). RESULTS: VDR/RXRA expressions were significantly higher in ß-thalassemia children compared to controls (P = 0.001 and <0.001, respectively) and showed higher values in ß-thalassemia major relative to ß-thalassemia intermedia. Expression levels of both genes were not associated with sex or BMD. However, VDBP rs4701 genotyping revealed lower BMD-L4 and a higher frequency of osteoporosis. CONCLUSIONS: ß-Thalassemia children had higher expression levels of PBMN VDR/RXRA. VDBP rs4701 variant was associated with osteoporosis in our ß-thalassemia patients on vitamin D supplementation. Further large-scale studies in other ethnic populations are warranted.