Vitamin D Receptor Gene Haplotypes and Susceptibility to HIV‐1 Infection in Injection Drug Users

Torre, M. Sanchez De La; Torres, Carmen de; Nieto, Gema; Vergara, Salvador; Carrero, Antonio José Carrero; Macı́as, Juan; Pineda, Juan A.; Caruz, Antonio; Fibla, Joan

doi:10.1086/525043

Cited by 62 publications

(63 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it is difficult to ascribe variations in the Bsm1 genotype to changes in VDR function. Another recent study found no association between a specific polymorphism and protection against HIV infection in a population of injection drug users, but it did find a correlation between specific VDR haplotypes (blocks of polymorphisms) (23). The authors concluded that protective VDR polymorphisms were associated with reduced VDR function, consistent with vitamin D signal-ing promoting HIV infection, and noted based on an in vitro study that the 1,25D-bound VDR could activate the HIV type 1 long terminal repeat (61).…”

Section: Vdr Gene Polymorphisms and Infectious Diseasesmentioning

confidence: 88%

Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity

2008

View full text Add to dashboard Cite

Vitamin D was first identified as a cure for nutritional rickets, a disease of bone growth caused by an inadequate uptake of dietary calcium. It is now known that vitamin D can be obtained through two independent pathways: limited dietary sources and the photochemical action of solar UV light in the skin. Cod liver oil was discovered to be an excellent source of antirachitic activity in 1827, although it was not until several decades later that the active ingredient was identified as vitamin D 3 . Even earlier, in 1822, a Polish physician studying children reached the remarkable conclusion that sunlight cured rickets after noting that rickets was relatively rare in the clearer air of rural areas. Almost 100 years later, in 1919, it was shown that artificial UV light cured rickets (49; www .beyonddiscovery.org/Includes/DBLink.asp?IDϭ1176). Indeed, secosteroidal vitamin D 3 is produced in the skin via photochemical and thermal conversion of 7-dehydrocholesterol in the presence of UVB light (ϳ295 to 320 nm). While it seems that vitamin D is readily accessible via dietary or solar routes, vitamin D insufficiency or deficiency is, in fact, quite widespread. Solar UVB irradiation is absorbed by atmospheric ozone; consequently, the surface intensity of UVB varies markedly with latitude and time of year. Moreover, as vitamin D intake is generally inadequate in most diets (38-40), the rate of vitamin D insufficiency or deficiency increases with increasing latitude.The term vitamin D refers collectively to vitamin D 3 and vitamin D 2 , which is derived from irradiation of the steroid ergosterol in yeast. Biologically active vitamin D is generated via largely hepatic 25-hydroxylation catalyzed by CYP2R1, CYP27A1, and possibly other enzymes to produce 25-hydroxvitamin D (25D) (21,40,43,67,81), which has a long half-life and is the major circulating vitamin D metabolite. 25D is modified by 1␣-hydroxylation catalyzed by CYP27B1, which produces hormonal 1,25-dihydroxyvitamin D (1,25D) (40,43,67). Vitamin D compounds are catabolized via 24-hydroxylation by CYP24, whose expression is strongly inducible by 1,25D, which constitutes a negative feedback loop (40,43,67).While the kidneys are a major site of 1␣-hydroxylation of 25D, it has recently become clear that generation of hormonal 1,25D in peripheral tissues is critical to the full scope of the physiological actions of this compound. Renal 1␣-hydroxylation is tightly controlled by calcium homeostatic signals, particularly circulating parathyroid hormone (PTH). Although initially characterized as a calcium homeostatic agent, vitamin D is now known to have pleiotropic actions, including a key role in immune system regulation (49). Importantly in this regard, recent research detailed here has uncovered critical, cell-specific differences in both the regulation of 1␣-hydroxylation of 25D and 24-hydroxylation that are relevant to the role of 1,25D as an immune system regulator. VITAMIN D INSUFFICIENCY/DEFICIENCY AND DISEASEWhile there is no strict definition, vitamin D deficiency i...

show abstract

Section: Vdr Gene Polymorphisms and Infectious Diseasesmentioning

confidence: 88%

Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity

2008

View full text Add to dashboard Cite

show abstract

“…Acute lower respiratory infections are one of the commonest reasons for hospital emergency department presentations, hospitalization and intensive care unit admissions among children. 38 Evidence exists that vitamin D may have a protective role in influenza 16,39 and other viral diseases, such as the risk of developing acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV), 40 hepatitis, 41 Avian flu, 42 and other viral infections. Studies dating back to the 1940s have associated a diet poor in vitamin D with susceptibility to experimental influenza viruses in mice.…”

Section: Antimicrobial Efficacy Against Different Infective Agentsmentioning

confidence: 99%

“…Polymorphisms in the structure of the VDR gene directly affect host susceptibility to HIV infection, CD4 counts, immunological hyperactivity and rapidity of disease progression to full-blown AIDS. 40,63 The G-A-T-G-L haplotype of VDR (which confers a diminished efficacy of the vitamin D pathway) protects against transmission of HIV type 1 (possibly secondary to diminished antiviral chemokine release and an unbalanced Th2 response), 40 whereas in AIDS patients, the VDR BsmI BB and FokI heterozygosities are associated with a more accelerated CD4 drop and faster progression to AIDS. 64,65 cell production of IFNγ and IL-12, 95 modulating the immune response against M. tuberculosis, possibly reducing the risk of cytokine storm.…”

Section: Antimicrobial Efficacy Against Different Infective Agentsmentioning

confidence: 99%

Antimicrobial implications of vitamin D

Youssef

Miller

Elabbassi

et al. 2011

Dermato-Endocrinology

171

128

View full text Add to dashboard Cite

“…In addition, a group of 124 healthy white males recruited from anonymous blood donors from City of Jaen Hospital who tested negative for HIV-1 and HCV was used as a healthy control (HC) sample. The main epidemiological and clinical characteristics of the series studied were described previously (14). HIV-1 and HCV diagnostics were performed as previously described (14).…”

Section: Human Subjectsmentioning

confidence: 99%

“…The main epidemiological and clinical characteristics of the series studied were described previously (14). HIV-1 and HCV diagnostics were performed as previously described (14). All IDU-HESN individuals and their respective controls were Spanish of Caucasian origin.…”

Section: Human Subjectsmentioning

confidence: 99%

A Common Polymorphism in TLR3 Confers Natural Resistance to HIV-1 Infection

Sironi

Biasin

Cagliani

et al. 2012

The Journal of Immunology

Self Cite

108

View full text Add to dashboard Cite

TLR3 recognizes dsRNA and activates antiviral immune responses through the production of inflammatory cytokines and type I IFNs. Genetic association studies have provided evidence concerning the role of a polymorphism in TLR3 (rs3775291, Leu412Phe) in viral infection susceptibility. We genotyped rs3775291 in a population of Spanish HIV-1–exposed seronegative (HESN) individuals who remain HIV seronegative despite repeated exposure through i.v. injection drug use (IDU-HESN individuals) as witnessed by their hepatitis C virus seropositivity. The frequency of individuals carrying at least one 412Phe allele was significantly higher in IDU-HESN individuals compared with that of a matched control sample (odds ratio for a dominant model = 1.87; 95% confidence interval, 1.06–3.34; p = 0.023). To replicate this finding, we analyzed a cohort of Italian, sexually HESN individuals. Similar results were obtained: the frequency of individuals carrying at least one 412Phe allele was significantly higher compared with that of a matched control sample (odds ratio, 1.79; 95% confidence interval, 1.05–3.08; p = 0.029). In vitro infection assays showed that in PBMCs carrying the 412Phe allele, HIV-1Ba-L replication was significantly reduced (p = 0.025) compared with that of Leu/Leu homozygous samples and was associated with a higher expression of factors suggestive of a state of immune activation (IL-6, CCL3, CD69). Similarly, stimulation of PBMCs with a TLR3 agonist indicated that the presence of the 412Phe allele results in a significantly increased expression of CD69 and higher production of proinflammatory cytokines including IL-6 and CCL3. The data of this study indicate that a common TLR3 allele confers immunologically mediated protection from HIV-1 and suggest the potential use of TLR3 triggering in HIV-1 immunotherapy.

show abstract

Vitamin D Receptor Gene Haplotypes and Susceptibility to HIV‐1 Infection in Injection Drug Users

Cited by 62 publications

References 13 publications

Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity

Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity

Antimicrobial implications of vitamin D

A Common Polymorphism in TLR3 Confers Natural Resistance to HIV-1 Infection

Contact Info

Product

Resources

About