vitamin D Receptor Gene HIV

Tuberculosis (TB) is the frequent major opportunistic infection in HIV-infected patients, and is the leading cause of mortality among HIV-infected patients. Genetic susceptibility to TB in HIV negative subjects is well documented. Since coinfections can influence the way in which immune system respond to different pathogens, genetic susceptibility to TB in HIV patients might also change. Studies from India and other parts of the world have shown that genetic susceptibility to TB is influenced by HIV infection...

Skeletal muscle wasting is an important public health problem associated with aging, chronic disease, cancer, kidney dialysis, and HIV/AIDS. 1,25-Dihydroxyvitamin D (1,25-D3), the active form of vitamin D, is widely recognized for its regulation of calcium and phosphate homeostasis in relation to bone development and maintenance and for its calcemic effects on target organs, such as intestine, kidney, and parathyroid glands. Emerging evidence has shown that vitamin D administration improves muscle performance and reduces falls in vitamin D-deficient older adults...

Vitamin D plays a major role in bone mineral density and calcium homeostasis. Apart from its classical action, the active form of vitamin D [1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))] influences the innate and adaptive immune functions through vitamin D receptor (VDR) that are present in various cells of the immune system. Vitamin D deficiencies have been associated with development of tuberculosis (TB) disease, caused by Mycobacterium tuberculosis. Vitamin D(3) is shown to enhance macrophage phagocytosis of M...

Vitamin-D-receptor (VDR) mediates immunomodulatory effects of vitamin-D₃ (VD₃). The VDR-rs1544410_GG polymorphism has been associated with delayed progression rates to AIDS and resistance to HIV-1 infection. The aim of the present study was to investigate differences in VD₃ mediated effects on rs1544410 genotyped dendritic cells (DCs) and macrophages (MDM), key cells involved in HIV-1 infection. Immature DCs exhibited lower b-actin-normalized VDR mRNA expression in rs1544410_GG compared to cells with a rs1544410_AA genotype...

Toll-like, vitamin A and D receptors and other innate proteins participate in various immune functions. We determined whether innate gene-sequence variations are associated with rubella vaccine-induced cytokine immune responses. We genotyped 714 healthy children (11-19 years of age) after two doses of rubella-containing vaccine for 148 candidate SNP markers. Rubella virus-induced cytokines were measured by ELISA. Twenty-two significant associations (range of P values 0.002-0.048) were found between SNPs in the vitamin A receptor family (RARA, RARB, TOP2B and RARG), vitamin D receptor and downstream mediator of vitamin D signaling (RXRA) genes and rubella virus-specific (IFN-gamma, IL-2, IL-10, TNF-alpha, and GM-CSF) cytokine immune responses...

Human immunodeficiency virus-1 (HIV-1) in acquired immune deficiency syndrome (AIDS) relies on human host cell proteins in virtually every aspect of its life cycle. Knowledge of the set of interacting human and viral proteins would greatly contribute to our understanding of the mechanisms of infection and subsequently to the design of new therapeutic approaches. This work is the first attempt to predict the global set of interactions between HIV-1 and human host cellular proteins. We propose a supervised learning framework, where multiple information data sources are utilized, including co-occurrence of functional motifs and their interaction domains and protein classes, gene ontology annotations, posttranslational modifications, tissue distributions and gene expression profiles, topological properties of the human protein in the interaction network and the similarity of HIV-1 proteins to human proteins' known binding partners...

INTRODUCTION: Vitamin D receptor (VDR) gene polymorphisms in the 5' regulatory region (Cdx2 and A-1012G), coding region (FokI), and 3' untranslated region (UTR; BsmI, ApaI, and TaqI) were studied to find out whether these polymorphisms are associated with susceptibility to or protection against HIV-1 and development of tuberculosis (TB) in human immunodeficiency virus (HIV)-1-infected patients. STUDY SUBJECTS AND METHODS: The study was carried out in 131 HIV patients without TB (HIV+ TB-) and 113 HIV patients with TB (HIV+ TB+; includes 82 patients with pulmonary TB (HIV+ PTB+) and 31 with extra pulmonary TB), 108 HIV-negative pulmonary TB patients (HIV- PTB+), and 146 healthy controls...

Reverse transcriptase (RT) inhibitors are emerging as a novel class of anticancer differentiating agents, active in several human tumor cell models, such as melanoma and prostate, thyroid and colon carcinoma. Indeed, much evidence suggests that they may act by inhibiting endogenous RT, a gene highly expressed in undifferentiated and transformed cells. We therefore evaluated whether endogenous RT may represent a new molecular target in the treatment of human renal clear-cell carcinoma, a neoplasm with very low sensitivity to standard pharmacological therapies...

Vitamin D receptor (VDR) participates in multiple immune functions. Here, we determined whether VDR gene-sequence variations are associated with intersubject differences in the risk of acquiring human immunodeficiency virus type 1 (HIV-1) infection. We assessed this in 460 males exposed to HIV-1 by injection drug use (335 infected and 125 uninfected) and 124 seronegative healthy subjects. Multilocus logistic regression analysis revealed haplotypes for rs11568820, rs4516035, rs10735810, rs1544410, and rs17878969 polymorphisms showing association with protection to HIV-1 infection (odds ratio, 0...

Drug-drug interactions involving induction of cytochrome P450 enzymes (P450s) can lead to loss of drug efficacy. Certain drugs, particularly those used to treat mycobacterial and human immunodeficiency virus (HIV) infections, are especially prone to induce P450s. During studies to examine drug-interaction potential of compounds in cultured human hepatocytes, exposure with (S)-1-[(1S,3S,4S)-4-[(S)-2-(3-benzyl-2-oxo-imidazolidin-1-yl)-3,3-dimethyl-butyrylamino]-3-hydroxy-5-phenyl-1-(4-pyridin-2-yl-benzyl)-pentylcarbamoyl]-2,2-dimethyl-propyl-carbamic acid methyl ester (A-792611), a novel HIV protease inhibitor (PI) previously under investigation for the treatment of HIV infection, resulted in significant down-regulation of constitutive CYP3A4 expression...

The genetic predisposition of the host and the virus is the most important determinant for prediction of the course of human immunodeficiency virus type I (HIV-1) viral infection and acquired immune deficiency syndrome (AIDS) progression. Transcription from the HIV-1 long terminal repeat (LTR) is a crucial step for viral replication. Here, we describe a stimulatory role of the vitamin D receptor (VDR) on HIV-1 LTR transactivation. Transient transfections reveal that VDR activates the LTR in HeLa, U937, and Cos-1 cells in a ligand-dependent manner...

Genetic susceptibility towards clinical tuberculosis has been proposed in several population studies. We investigated whether polymorphisms in the candidate genes encoding solute carrier 11a1 protein (SLC11A1 formerly NRAMP1), mannose-binding lectin (MBL2) and Vitamin D receptor (VDR) were associated with tuberculosis in an East-African setting. Four hundred and forty-three culture positive pulmonary tuberculosis patients and 426 controls from Mwanza district in the northern part of Tanzania were prospectively included...

It is becoming widely accepted that psychoactive drugs can significantly alter the progression of neuropathological changes in the HIV-infected brain. The use of cocaine can aggravate the neurotoxic effects of HIV-1 proteins such as HIV-1 transactivating protein Tat and virus' envelope protein gp120. HIV-1 Tat is believed to play an important role in pathogenesis of HIV dementia (HAD). Tat is neurotoxic and a constantly growing body of evidence suggests that the toxic effects of Tat are oxidative stress-dependent...

Twenty-seven polymorphisms from 12 genes have been investigated for association with tuberculosis (TB) in up to 514 cases and 913 controls from Karonga district, northern Malawi. Homozygosity for the complement receptor 1 (CR1) Q1022H polymorphism was associated with susceptibility to TB in this population (odds ratio [OR] = 3.12, 95% Confidence interval [CI] = 1.13-8.60, P = 0.028). This association was not observed among human immunodeficiency virus (HIV)-positive TB cases, suggesting either chance association or that HIV status may influence genetic associations with TB susceptibility...

In addition to its role in mineral metabolism, 1,25-dihydroxivitamin D3 (1,25(OH)2D3) also has immunomodulatory effects. Vitamin D receptor (VDR) mediates genomic actions of 1,25(OH)2D3, by acting as a transcription factor that modulates the expression of several 1,25(OH)2D3 response genes. Variations at the VDR locus have been associated with susceptibility and progression to several immune diseases. We investigated the association between rates of progression to acquired immunodeficiency syndrome (AIDS) and the Fok-I polymorphism, which is located at the initiation codon of the VDR gene...

The effect of polymorphisms on genes encoding the CCR5 chemokine receptor and vitamin D receptor (VDR) in human immunodeficiency virus (HIV) type 1 disease progression was analyzed in a cohort of 185 HIV-seropositive injection drug users. Results confirmed a lack of association in patients with HIV disease between CCR5 wtDelta32 heterozygosity and a slow progression to AIDS and to a CD4 cell count <200 cells/microL. In contrast, a more rapid disease progression was associated with the VDR-BB genotype. A higher proportion of this genotype was found in patients with <200 CD4 cells/microL (P=...

Twin and adoptee studies have indicated that host genetic factors are major determinants of susceptibility to infectious disease in humans. Twin studies have also found high heritabilities for many humoral and cellular immune responses to pathogen antigens, with most of the genetic component mapping outside of the major histocompatibility complex. Candidate gene studies have implicated several immunogenetic polymorphisms in human infectious diseases. HLA variation has been associated with susceptibility or resistance to malaria, tuberculosis, leprosy, AIDS, and hepatitis virus persistence...

We have examined the 5' flanking region of the mouse calbindin-D28k gene and identified a 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-responsive element by deletion mutant analysis of the native promoter as well as by studies with a heterologous thymidine kinase (TK) promoter. The segment between residues -200 and -169 was found to confer a dose-dependent 1,25-(OH)2D3 responsiveness through the TK promoter in Ros 17/2.8 cells as well as in CV-1 cells cotransfected with pAV-hVDR (human vitamin D receptor expression vector)...