Vitamin D and Viruses that can trigger Me/CFS

percyval577

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EBV, CMV and one Enterovirus have been found to act on the vitamin D recpetor VDR.
HCV is associated with vitamin D, Parvovirus can be associated.
HHV-6 comes up with only one (negative) finding in respect of vitamin D, but can be associated.
____________​

Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes.
Yenamandra et al 2010


Abstract (my paragraphing)
Epstein-Barr virus (EBV) is a human gamma herpes virus that infects B cells and induces their transformation into immortalized lymphoblasts that can grow as cell lines (LCLs) in vitro. EBNA-3 is a member of the EBNA-3-protein family that can regulate transcription of cellular and viral genes.

The identification of EBNA-3 cellular partners and a study of its influence on cellular pathways are important for understanding the transforming action of the virus.

In this work, we have identified the vitamin D receptor (VDR) protein as a binding partner of EBNA-3. We found that EBNA3 blocks the activation of VDR-dependent genes and

protects LCLs against vitamin-D3-induced growth arrest and/or apoptosis. The presented data shed some light on the anti-apoptotic EBV program and the role of the EBNA-3-VDR interaction in the viral strategy.
paywalled
Cell Mol Life Sci. 2010 Dec;67(24):4249-56. doi: 10.1007/s00018-010-0441-4. Epub 2010 Jul 1.
 
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percyval577

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Human cytomegalovirus infection downregulates vitamin-D receptor in mammalian cells.
Rieder et al 2017


Abstract (my paragraphing)
Vitamin D (VD) is essential for the human body and involved in a wide variety of critical physiological processes including bone, muscle, and cardiovascular health, as well as innate immunity and antimicrobial responses. Here, we elucidated the significance of the VD system in cytomegalovirus (CMV) infection, which is one of the most common opportunistic infections in immunocompromised or -suppressed patients.

We found that expression of vitamin D receptor (VDR) was downregulated in CMV-infected cells within 12h [hrs] post infection [p.i.] to 12% relative to VDR expression in mock-infected fibroblasts and did not recover during the CMV replication cycle of 96h.

None of the biologically active metabolites of VD, cholecalciferol, calcidiol, or calcitriol, inhibit CMV replication significantly in human fibroblasts. In a feedback loop, expression of CYP24A1 dropped to 3% by 12h p.i. and expression of CYP27B1 increased gradually during the replication cycle of CMV to 970% probably as a consequence of VDR inhibition.

VDR expression was not downregulated during influenza virus or adenovirus replication. The potent synthetic vitamin D analog EB-1089 was not able to inhibit CMV replication or antagonize its effect on VDR expression. Only CMV replication, and none of the other viral pathogens evaluated, inhibited the vitamin D system in vitro.

In view of the pleiotropism of VDR, CMV-mediated downregulation may have far-reaching virological, immunological, and clinical implications and thus warrant further evaluations in vitro and in vivo.
open acces
J Steroid Biochem Mol Biol. 2017 Jan;165(Pt B):356-362. doi: 10.1016/j.jsbmb.2016.08.002. Epub 2016 Aug 9.
 

percyval577

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an enterovirus:

Vitamin D receptor protects glioblastoma A172 cells against Coxsackievirus A16 infection induced cell death in the pathogenesis of hand, foot, and mouth disease.
Qu et al 2017


Abstract (my pragraphing)
Hand, foot, and mouth disease (HFMD) was one of the most common children illnesses. Coxsackievirus A16 was one of the major pathogens that cause HFMD.

However, the role of vitamin D underlying this common illness has not been elucidated. Our study examined that vitamin D levels was significantly lower in 33 HFMD patients, compared to 36 healthy children.

Unexpectedly, both mRNA and protein expression of VDR were significantly decreased in CA16 infected glioblastoma A172 cells. And overexpression of VDR or vitamin D treatment in CA16 infected glioblastoma A172 cells could reverse the CA16 infection induced cell death, apoptosis or mitochondrial membrane rupture.

Therefore, our study, for the first time, demonstrated that vitamin D and VDR could associate with the pathogenesis of HFMD. Thus might provide useful information for HFMD prevention and treatments.
paywalled
Biochem Biophys Res Commun. 2017 Nov 18;493(2):952-956. doi: 10.1016/j.bbrc.2017.09.112. Epub 2017 Sep 21.
 
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percyval577

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this might be not too conclusive:

Association between vitamin D and hepatitis C virus infection: A meta-analysis.
Villar et al 2013


Abstract
AIM: To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and sustained virological response (SVR) in hepatitis C virus (HCV) infected individuals.

METHODS: Relevant studies were identified by systematically searching MEDLINE databases up to March 2012 and abstracts of the European and American Congress of Hepatology conducted in 2011. Studies must provide information on SVR and the levels of 25(OH)D3 and/or 25(OH)D2 [henceforth referred to as 25(OH)D] in sera samples from HCV infected individuals. The inclusion criteria were: clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group; provided information on SVR rates; and were reported in the English language as full papers. Due to the heterogeneity of studies in categorizing serum vitamin D levels, a cut-off value of 30 ng/mL of serum 25(OH)D was used. Heterogeneity was assessed using I2 statistics. The summary odds ratios with their corresponding 95%CI were calculated based on a random-effects model.

RESULTS: Overall, 11 studies (8 observational and 3 interventional) involving 1575 individuals were included and 1117 HCV infected individuals (71%) showed low vitamin D levels. Most of the studies included mono-infected HCV individuals with the mean age ranging from 38 to 56 years. Four studies were conducted in human immunodeficiency virus/HCV infected individuals. Regarding vitamin D measurement, most of the studies employed radioimmunoassays (n = 5) followed by chemiluminescence (n= 4) and just one study employed high performance/pressure liquid chromatography (HPLC). Basal vitamin D levels varied from 17 to 43 ng/mL in the studies selected, and most of the HCV infected individuals had genotype 1 (1068/1575) with mean viral load varying from log 4.5-5.9 UI/mL. With regard to HCV treatment, most of the studies (n = 8) included HCV individuals without previous treatment, where the pooled SVR rate was 46.4%. High rates of SVR were observed in HCV individuals with vitamin D levels above 30 ng/mL (OR = 1.57; 95%CI: 1.12-2.2) and those supplemented with vitamin D (OR = 4.59; 95%CI: 1.67-12.63) regardless of genotype.

CONCLUSION: Our results demonstrated high prevalence of vitamin D deficiency and high SVR in individuals with higher serum vitamin D levels or receiving vitamin D supplementation.
open acces
World J Gastroenterol. 2013 Sep 21; 19(35): 5917–5924. Published online 2013 Sep 21. doi: 10.3748/wjg.v19.i35.5917
 
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percyval577

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speculative linkage with two reviews:

The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmunedisease.
Jonathan Kerr 2015


Abstract (my paragraphing)
Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised.

Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic.

Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus.

B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein.
open acces
J Clin Pathol. 2016 Apr;69(4):279-91. doi: 10.1136/jclinpath-2015-203455. Epub 2015 Dec 7.

note that Jonathan Kerr in his recent article on ME/CFS judged that it would be an "autoimmune-like disease"


Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential.
Dankers et al 2017


Abstract (my paragraphing)
Over the last three decades, it has become clear that the role of vitamin D goes beyond the regulation of calcium homeostasis and bone health. An important extraskeletal effect of vitamin D is the modulation of the immune system.

In the context of autoimmune diseases, this is illustrated by correlations of vitamin D status and genetic polymorphisms in the vitamin D receptor with the incidence and severity of the disease. These correlations warrant investigation into the potential use of vitamin D in the treatment of patients with autoimmune diseases. In recent years, several clinical trials have been performed to investigate the therapeutic value of vitamin D in multiple sclerosis, rheumatoid arthritis, Crohn's disease, type I diabetes, and systemic lupus erythematosus.

Additionally, a second angle of investigation has focused on unraveling the molecular pathways used by vitamin D in order to find new potential therapeutic targets. This review will not only provide an overview of the clinical trials that have been performed but also discuss the current knowledge about the molecular mechanisms underlying the immunomodulatory effects of vitamin D and how these advances can be used in the treatment of autoimmune diseases.
open acces
Front Immunol. 2017 Jan 20;7:697. doi: 10.3389/fimmu.2016.00697. eCollection 2016.
 
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percyval577

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for HVV-6 google told only one negative finding:

Vitamin D serum levels and viral load of human herpesvirus and Epstein-Barr virus in patients with multiple sclerosis after one year of follow up.
Alvarez-Lafuente 2017


Abstract
Background: Low levels of 25-hydroxyvitamin D (25-(OH)D2) have been described as one of the possible environmental factors involved in multiple sclerosis (MS) etiopathogenesis. In addition, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) infection have also been proposed as MS triggers. A possible effect of vitamin D levels on viral status have been suggested.

Objectives: To analyse the replication/reactivation of EBV and HHV-6 in MS patients regarding the serum levels of 25-(OH)D2, in order to investigate the possible relationship between vitamin D levels and viral status.

Methods: 200 MS patients were included in this retrospective longitudinal study of one year follow-up. For each one of the patients, two peripheral blood and serum samples were collected, in such a way that data were obtained from both semesters of the year. DNA was extracted from blood in order to analyse EBV and HHV-6 viral load in peripheral blood cells by quantitative real-time PCR. 25-(OH)D2 was determined using a delayed one step chemiluminiscent microparticle immunoassay (Abbott) from serum samples.

Results: The median value for 25-(OH)D2 in the first semester of the year among the MS patients included in the study was 17.5 ng/ml (ranging between 15.5 ng/ml in March and 19.3 ng/ml in June); the median value for 25-(OH)D2 in the second semester of the year was 24.6 ng/ml (ranging between 19.6 ng/ml in December and 28.4 ng/ml in September). In the first semester of the year, 22% of MS patients were positive by qPCR for EBV when 25-(OH)D2< 11 ng/ml, and only just 4% were positive when 25-(OH)D2>20 ng/ml (p=0.03). In addition, EBV viral load was higher in those MS patients with lower 25-(OH)D2 levels, compared to those with levels above 20 ng/ml (p=0.04).
For HHV-6, there were no differences between MS patients with high and low 25-(OH)D2 levels. Moreover, no differences were found in the second semester of the year, neither for EBV nor HHV-6, when 25-(OH)D2 levels were higher and only 28.4% of the samples had levels < 20 ng/ml in comparison with the 64.3% in the first semester of the year.

Conclusions: Vitamin D levels could be involved in the regulation of the replication/reactivation of EBV in peripheral blood cells of MS patients; moreover, viral load seems to be higher when 25-(OH)D2 levels in serum are low. Further studies, also in healthy controls, are required.
paywalled.
 

percyval577

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via telomeres there can be made an association between HHV-6 and vitamin D:

HHV-6A/B Integration and the Pathogenesis Associated with the Reactivation of Chromosomically Integrated HHV-6A
Collin and Flammand 2017


5.2
For most herpesviruses, integration into host chromosomes is an unusual event. In some cases, it was observed that in the presence of DNA breaks induced by UV radiation, human herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) can integrate into chromosomes. However, the integrated HSV-1 and HSV-2 genome were fragmented and mutated, not able to generate new virions [72]. In contrast to HSV-1 and HSV-2, HHV-6A/B integrated genomes remain largely intact with their ORFs conserved.
7. Conclusions
Though reported 25 years ago, the study of HHV-6A/B integration remains understudied. With the development of HHV-6A/B integration systems [86] and genome editing technologies, scientists should be able to tease out in detail the mechanisms leading to viral integration. Considering a prevalence of approximately 1%, pinpointing the association between iciHHV-6A/B and diseases is not trivial. This will require considerable effort, funding and access to large biobanks linked to detailed medical records. Scientists will likely need to share and pool their data to reach meaningful conclusions, especially for less-prevalent diseases. Furthermore, considering that appearance of a disease is likely to be influenced by the chromosome carrying the integrated HHV-6A/B as well of the sex of the individual, these variables should be taken into consideration during data analyses.
open acces
Viruses. 2017 Jun 26;9(7). pii: E160. doi: 10.3390/v9070160.



The role of telomeres and vitamin D in cellular aging and age-related disease
Pusceddu et al 2015


Studies in humans, page 1671, my paragraphing
A summary of the literature data regarding the link between telomere biology and vitamin D is reported in Table 1.

Richards et al. were the first to demonstrate a positive correlation between serum 25-OHD and LTL in humans, which remained significant after adjustment for age [139]. In their study they analyzed 2160 women of the TwinsUK cohort. After multiple adjustments for age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy and physical activity, the difference in telomere length between the highest (124±37.3 nmol/L) and lowest (40.9±11 nmol/L) tertile of 25-OHD concentrations was equivalent to 5 years of telomeric aging [139]. In addition, the authors analyzed a subpopulation of 700 women that used vitamin D supplements. On average, these women had longer telomeres than women who did not use vitamin D supplements. However this difference was not statistically significant.

These initial findings were confirmed by a subsequent study performed by Liu et al. [143]. In this study, analyses were performed on 1424 women of the Nurses’ Health Study and the results showed a positive correlation between LTL and serum 25-OHD concentrations. Logistic regression analysis indicated a concentration-dependent relationship. However, calcium intake modified this association significantly. 1,25(OH)2 D was also measured, but did not correlate with LTL.

As single nucleotide polymorphisms (SNPs) in genes involved in vitamin D metabolism (like SNPs in VDR, VDBP CYP2R1 and DHCR7), are reported to affect vitamin D blood concentrations, Liu et al. analyzed vitamin D-related SNPs in their population. They identified a positive association between rs7041 and rs4588 (both SNPs of VDBP), and 25-OHD levels. However, none of the investigated vitamin D-related SNPs were significantly associated with LTL [143].

Beside these cross-sectional studies, only one interventional study has been performed in order to clarify the effect of vitamin D supplementation on telomere biology [141]. Zhu et al. treated 37 obese Afro-American subjects in a double-blind randomized fashion with either a monthly oral dose of 60,000 IU of vitamin D3 or placebo for a period of 4 months. At the end of the study the serum 25-OHD concentration in vitamin D treated subjects was markedly increased when compared to baseline. The rise in serum 25-OHD was accompanied by a 19.2% increase of peripheral blood mononuclear cell (PBMC) telomerase activity. In the placebo group no such changes were seen. However, LTL was not measured in this study, limiting also the power of their findings. Further support for vitamin supplementation preserving telomere length comes from a recent study in hemodialysis patients [140].

Borras et al. observed longer telomeres in hemodialysis patients treated with calcitriol or analogs for at least 6 months compared to hemodialysis patients without such treatment [140].

Finally, Hoffecker et al. reported a significant correlation between telomere length and serum 25-OHD concentrations in vitamin D deficient (serum 25-OHD  < 20 ng/mL) patients with systemic lupus erythematosus (SLE) and unaffected controls [142]. Moreover, patients with SLE whose serum 25-OHD concentrations remained insufficient/deficient ( < 30 ng/mL) after 2.8 years of follow-up had shorter telomeres than patients with a sufficient serum 25-OHD concentration ( > 30 ng/mL).
open acces
Clinical Chemistry and Laboratory Medicine 21.03.2015 | DOI: https://doi.org/10.1515/cclm-2014-1184

thread on telomeres
 

uglevod

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Sidny

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How it is possible to eradicate those viruses they are all intercellular...
Gene editing is showing promise in that regard. Technologies like DRACO and viralym-m seem like functional cures also.

Kieth Jerome at Fred hutch research center is working on endonucleases that apparently have been able to delete up to 90% of HSV in mouse ganglia. I think they’ve shown crispr as being effective for EBV already.
 

Sidny

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This still does not prove that raising the levels of Vit D via sun/supplements will magically low EBV load. Separate in-vivo study is required.
Agreed. If various viruses such as EBV are down regulating and interfering with vitamin D receptor function I’m not sure how simply supplemeting with it will make much of a difference.

In that sense I think lowering EBV load through antivirals or other means might actually work better to raise vitamin D.

The links @percyval577 posted seem to indicate it’s not so much about what vitamin d levels are but how these pathogens prevent the body from utilizing it appropriately.

The Marshall protocol seems to take much of this into consideration although I think avoiding vitamin d all together can be problematic in its own right.
 

Gingergrrl

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Thank you for linking me to this thread @percyval577. My situation is that I currently take 10,000 IU's per day of Vit D3 yet my Vit D level on blood tests continues to drop and is now at 26 (on the US scale which I know is different than the UK scale). I just switched brands of Vit D3 (as of today) and I am also now taking it with food (in case either of these factors can help).

In reading this thread, I am now wondering what role EBV played in my Vit D being so low. I had very severe Mono from EBV in 2012 which started this whole thing (although I had several other immune system triggers right before and right after having Mono/EBV). In addition, I have the VDR Taq mutation (SNP?) on 23andMe although I am not sure that I can explain how this factors in. I guess it means I was pre-disposed genetically and now combined with the EBV, I cannot maintain a normal level of Vit D.

The other factor (in my case) is that I cannot maintain normal levels of other things (besides Vit D) without supplementation (like iron, B-12, Folate, Potassium, and now even my thyroid medication). So my doctors think I have a malabsorption issue from MCAS. But the EBV part is interesting, too. I just wanted to post this in case it is helpful to anyone else.
 

percyval577

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@Gingergrrl I have a few brainstorming points
  • in plants manganese increases potassium. EBV has been found to cause Mn-SOD2 autoantibodies, and has been found to increase potassium channels.
  • iron competes with manganese for the same transporter in the blood (DMT-something I believe)
  • the VDR induces downstream the cytosolic zinc/manganese transporter ZnT10 which transports Mn out if the cell, as well as into the golgi apperatus, as well as into exosomes
this doesn´t make a whole story in your case: if you had too much manganese inside the cell then the iron/manganese transporter might become downregulated, but why would the uptake of the helpful VitD get downregulated? Maybe the amount of receptors does an announce that there isn´t much VitD required??
  • magnesium acts with enzymes which often also can use manganese, though there are some typical manganese enzymes which don´t use magnesium (as far as I have pursued)
  • melatonin is the counterhormone to VitD, there is a synergistic action of zinc with melatonin
  • caffein decreases VDR expression
I will try to give the literature "soon" (planning a few more threads).
threads/melatonin-and-zinc.77286/ (here also thyroid interactions)
threads/vitamin-d-and-zinc-manganese.77285/ (including hemeoxigenase1, if this can mean anything)

(If you take zinc, it could be a good idea to take it towards the evenenig, I personally now take some VitD, though only in the morning, and eating some melatonin containing food in the evening).

With the Coxsackie A virus I was inaccurate, this virus is not known for causing mecfs, so a counterexample, on the other hand, it might say that the A ones simply lack another virulent property whichthough would be present in the B ones, as a simple relationship is unlikely anyway.
 
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percyval577

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@Hip provided me (post) with a potential link between an enterovirus which is known for triggering ME/CFS and VitD.
It might indicate that blocking the VitD Receptor or something like that would help the pathogen.

Mouse ß-Defensin 3 protects against Coxsackievirus B3 induced Myocarditis in mice
Jiang et al 2015

from the Abstract
CVB3-infected HeLa cells were treated with rMBD3, and the titer of CVB3 and the proliferative activities of the cells were determined. CBV3-infected BALB/c mice were divided into five groups: rMBD3 high (5 mg/kg/day, q.d.), rMBD3 low (2.5 mg/kg/day, q.d.), ribavirin (10 mg/kg/day, q.d.), normal control, and myocarditis control. On days 5 and 12 after treatment, 3 mice from each group were sacrificed and serum lactate dehydrogenase, creatine kinase-MB isozyme, and tumor necrosis factor-α levels were determined. The heart index and the inflammation of myocardial tissue were also assessed. On day 5, the CVB3 50% tissue culture infective dose (TCID50) values of heart tissues were measured.
RESULTS:
rMBD3 inhibited the replication of CVB3 and protected HeLa cells from infection. rMBD3 reduced the CVB3 titer markedly and inhibited the pathological reaction of cardiac myocytes to viral myocarditis. Treatment with rMBD3 improved the cell survival rate and reduced the cardiac index.
open access
Intervirology. 2015;58(6):343-9. doi: 10.1159/000442588. Epub 2016 Feb 2.

Multiple ß-defensin genes are upregulated by the vitamin D pathway in cattle
Merriman et al 2015

Abstract
Experimental models of bacterial and viral infections in cattle have suggested vitamin D has a role in innate immunity of cattle. The intracrine vitamin D pathway of bovine macrophages, however, has only been shown to activate a nitric oxide-mediated defense mechanism, as opposed to cathelicidin and β-defensin antimicrobial peptides in human macrophages.

In this study we have investigated the actions of 1,25-dihydroxyvitamin D3 (1,25D) on a cluster of eleven bovine β-defensin genes on the basis of RNAseq data indicating they were targets of 1,25D in cattle. Treatment of bovine monocyte cultures with 1,25D (10 nM, 18 h) in the absence and presence of LPS stimulation increased the expression of bovine β-defensin 3 (BNBD3), BNBD4, BNBD6, BNBD7, and BNBD10 genes 5 to 10-fold compared to control (P<0.05). Treatment of lipopolysaccharide (LPS)-stimulated monocytes with 0-100 ng/mL 25-hydroxyvitamin D3 also increased BNBD3, BNBD4, BNBD7, and BNBD10 in a dose-dependent manner.

Treatment of monocytes with the protein translation inhibitor, cycloheximide, however, blocked upregulation of the β-defensins in response to 1,25D suggesting the β-defensins in cattle are not direct targets of the vitamin D receptor. Furthermore, preliminary investigation of vitamin D's contribution to β-defensin expression in vivo revealed that intramammary 1,25D treatment of lactating cows increased BNBD7 expression in mammary macrophages.

In conclusion, our data demonstrate that multiple β-defensin genes are upregulated by 1,25D in cattle, providing further indication that vitamin D contributes to bovine innate immunity.
paywalled
J Steroid Biochem Mol Biol. 2015 Nov;154:120-9. doi: 10.1016/j.jsbmb.2015.08.002. Epub 2015 Aug 5.

Unspecificly for enteroviruses in generel:

Vitamin D status, enterovirus infection and type 1 diabetes in Italian children/adolescents.
Federico et al 2018


Abstract (my prgrphs)
At the time of the clinical onset of type 1 diabetes (T1D), we investigated 82 pediatric cases in parallel with 117 non-diabetic controls matched by age, geographic area, and time of collection. The occurrence of an enteroviral infection was evaluated in peripheral blood using a sensitive method capable of detecting virtually all human enterovirus (EV) types.

While non-diabetic controls were consistently EV-negative, 65% of T1D cases carried EVs in blood.

The vitamin D status was assessed by measuring the concentration of 25-hydroxyvitamin D [25(OH)D] in serum. Levels of 25(OH)D were interpreted as deficiency (≤50 nmol/L), insufficiency (52.5-72.5 nmol/L), and sufficiency (75-250 nmol/L). In T1D cases, the median serum concentration of 25(OH)D was 54.4 ± 27.3 nmol/L vs 74.1 ± 28.5 nmol/L in controls (P = .0001).

Diabetic children/adolescents showed deficient levels of vitamin D 25(OH)D (ie, 72.5 nmol/L) in 48.8% cases vs 17.9% in non-diabetic controls (P = .0001).

Unexpectedly, the median vitamin D concentration was significantly reduced in virus-positive vs virus-negative diabetics (48.2 ± 22.5 vs 61.8 ± 31.2 nmol/L; P = .015), with deficient levels in 58.5% vs 31.0%, respectively.


Thus, at the time of clinical onset, EV-positive cases had reduced vitamin D levels compared with EV-negative cases. This could indicate either that the virus-negative children/adolescents had been hit by a non-infectious T1D-triggering event, or that children/adolescents with proper levels of vitamin D had been able to rapidly clear the virus. Thus, it would be important to assess whether adequate vitamin D supplementation before or during the prediabetic phase of T1D may counteract the diabetogenic potential of infectious pathogens.
paywalled
Pediatr Diabetes. 2018 Aug;19(5):923-929. doi: 10.1111/pedi.12673. Epub 2018 Apr 17.
 
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percyval577

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Another known trigger:

Serum vitamin D levels are positively associated with varicella zoster immunity in chronic dialysis patients
Chao et al 2014


Conclusion
Vitamin D presumably has an immunoregulatory role and is involved for dialysis patients in the defense against infection. We found that 25-OH-D ≥ 27.8 ng/ml was positively associated with VZV-IgG levels in ESRD patients, suggesting potentially greater VZV-specific immunity. In addition, both higher total and bioavailable 25-OH-D correlated with higher VZV-IgG levels, whereas 1,25-(OH)2-D did not demonstrate such association. Judging from these findings, nutritional vitamin D may be a promising agent in our armamentarium by boosting immunity against herpes zoster in chronic dialysis patients.
open access
Sci Rep. 2014; 4: 7371.Published online 2014 Dec 9. doi:
10.1038/srep07371
 

percyval577

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It would be important, of course, that non-ME/CFS-triggers are not associated with an action on VitD.

Moreover, it would be comfortabely instructive if non-ME/CFS-trigger pathogens were not as vulnerable to VitD as ME/CFS triggers, otherwise findings which report that ME/CFS triggers are vulnerable wouldn´t say that much, so far.

Such a tendency may be seen indeed from this recent article:


Vitamin Supplementation at the Time of Immunization with a Cold-Adapted Influenza Virus Corrects Poor Mucosal Antibody Responses in Mice Deficient for Vitamin A and D
Surman et al 2016


Abstract (my prgrphs)
Vitamin A and D deficiencies and insufficiencies are prevalent worldwide in developed and developing countries. Vitamin metabolites are functionally intertwined in that they are high-affinity ligands for related receptors of the nuclear receptor superfamily. The effects of vitamin A deficiencies (VAD) on antibody responses to respiratory virus vaccines have already been demonstrated. Of particular concern was the reduction in IgA, a first line of defense against pathogens in the respiratory tract. Here, we describe the individual and combined effects of vitamin A and D deficiencies in mice immunized with an attenuated influenza virus vaccine.

Relative to VAD, vitamin D deficiency (VDD) had a limited effect, but double deficiencies for vitamins A and D (VAD+VDD) further reduced antibody responses in the respiratory tract.

The administration of supplemental vitamins A and D to VAD+VDD mice at the time of vaccination restored responses in a dose-dependent manner. Results suggest that vitamin supplementation programs may be beneficial in a clinical setting to promote healthy immune responses to respiratory virus vaccines in vitamin-deficient individuals.
open access
Clin Vaccine Immunol. 2016 Jan 6;23(3):219-27. doi: 10.1128/CVI.00739-15.

One must also critically say that even the ME/CFS trigger EBV itself seem not be vulnerable to VitD when replicating:
https://forums.phoenixrising.me/thr...s-linked-to-other-viruses.77780/#post-2231944
 
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Hip

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Yes, I've come across that study before, and it suggests that activation of the vitamin D receptor (VDR) inside the cell may stimulate the release of beta-defensin 3 in the cell, which may fight the chronic intracellular non-cytolytic enterovirus infections found in ME/CFS.

In the Marshall Protocol, the drug Benicar is used to activate the VDR. One study showed that isoleucine can help stimulate beta-defensin 3 secretion (in mice at least).
 

uglevod

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There is a critical difference: on MP, a proposed VDR agonist Benicar is used to bind with the receptors, while all above studies therapies/tests are based on VDR agonist precursors(D3 and D25). The main issue with D25(raised via D3/sun) is that it inducts hyperresponsiveness to bacterial patterns/toxins: https://www.sciencedaily.com/releases/2012/02/120223103920.htm

Also, D3->D25 immunosuppression favors accelerated tumor growth(by blunting down Th1 immune response):

Vitamin D aggravates breast cancer by inducing immunosuppression in the tumor bearing mouse:
https://www.ncbi.nlm.nih.gov/pubmed/29852828
The aim of this approach is to test the effects and related mechanism of vitamin D (VD) treatment on the outcomes of breast cancer. BALB/c mice were injected with 4T1 breast cancer cell suspension. The test group was treated with VD reagent. The survival and tumor size of mice were observed. The proliferation of 4T1 in vitro was detected by MTS analysis. The changes of immune parameters and microenvironment in mice were evaluated by flow cytometry and real-time RT-PCR. Our results demonstrate that VD administration caused a decline in survival time and raising the volume of tumor, the decreasing numbers of CD3+CD4+ T, CD3+CD8+ T and CD4+T-bet+IFN-γ+ Th1 cells and transcriptions of T-bet and IFN-γ, an increasing number of myeloid-derived suppressor cells and transcription of TGF-β. Our data suggest that the routine clinical application of any strategies targeting VD status for breast cancer therapy is deserved serious consideration.
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VD accelerated tumor growth & death of mice in 4T1 tumor-bearing mice Seventeen days after BALB/c mice were inoculated with 4T1 mammary carcinoma cells, the transplanted tumor was already obviously to be observed in the mice, then the tumor-bearing mice were orally treated with vehicle control (soybean oil) or VD for 1 week. Tumor growth was periodically measured and animals were monitored for survival outcome. As shown in Figure 2, around 10 days after 4T1 tumor cell inoculation, we can detect the tumor volume. With the time proceeding, the tumor growth showed a significant promotion in VD treatment mouse group. The tumor size in VD-treated group was bigger than the control group from day 31 postinoculation (Figure 2A) (p < 0.05). The survival rate in the VD-treated group was significantly shortened in comparison with that in the control group (Figure 2B). The result showed that VD could accelerate tumor growth and significantly shorten the survival of 4T1 tumor-bearing mice. On day 8 post VD treatment, we detected the concentrations of VD and calcium in the tumor-bearing mouse sera. The concentration of VD(detected as 25(OH)-Vitamin D)was higher than that of control group (p < 0.05), whereas the concentration of calcium had no difference in these two groups. The results were shown in Figure 3A & B.

VD treatment inhibited the systemic immune response in 4T1 tumor-bearing mice.

CD8+ cytotoxic T cells and Th1 cells curb cancer development via mechanisms commonly involving their production of cytotoxins and IFN-γ. To test whether VD treatment could inhibit the immune response mediated by T cells, we tested the numbers of CD3+CD4+, CD3+CD8+ and CD4+T-bet+IFN-γ+ T cells from splenocytes on day 25 and 32 postinoculation. Day 25 postinoculation marks the end of the VD oral administration. Day 32 postinoculation is the day of 1 week after VD oral administration. On day 32 postinoculation, the numbers of CD3+CD4+ (Figure 5A–C) and CD3+CD8+ (Figure 5D–F) T cells in VD treated group dramatically decreased. However, the Th1 cell and CD4+T-bet+IFN-γ+ cells were decreased on day 25 post inoculation (Figure 5G–I). These results indicated that the VD treatment affected the important T cell subsets proliferation, not only help T cell (CD4+) but also cytotoxic T cell (CD8+). Our data also investigated that the decrease of CD8+ T cells might be related to the Th1 cells, which was inhibited on earlier time.

VD has been increasingly recognized to have regulatory functions on both innate and adaptive immune [34]. The active form of VD (calcitriol [1,25(OH)2D3]) primarily affects DCs maturation and macrophage differentiation [35,36] and inhibits the production of the cytokines, IL-12 and IL-23. In addition, calcitriol directly acts on T cells to inhibit T-cell proliferation and IFN-γ production [37]. Moreover,calcitriol favors development of Tregs via modulation of DCs [38].Our data demonstrate that VD results in a decrease of the Th1 response in both spleen cells and tumor tissue. Also, suppressive cells of the innate arm of the immune system, such as inflammation-induced MDSCs, are known to be correlated with poor outcome and rapid disease progression [39,40]. MDSCs utilize a variety of mechanisms to suppress T-cell activation and induce other immune-suppressive cell populations [24]. On day 32 post inoculation, the number of MDSCs from spleen cells was dramatically increased. This change is consistent with the change of Th1-related cells. Collectively, these data are in line with earlier descriptions of the suppressive activities of VD with respect to the stimulation of Th1-mediated immunity.

Conclusion & future perspective

In summary, we demonstrate that VD treatment accelerates the growth of breast cancer in mice, which is closely associated with the activation of MDSCs. VD treatment suppressed the Th1 response in both system and tumor microenvironment. These results indicate that VD application might be associated with worse prognosis and seems to promote tumorigenesis. Therefore, these results would sugggest a thoughtful consideration for the routine application of VD replenishment to breast cancer prevention or therapy.
 

percyval577

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@uglevod
Another concern are kidney stones, at least when predispositioned.

However, the thread was in first order meant to grasp what might have happened during the trigger event.

Practically, with kidney stones one might avoid calcium rich foods, and it might be not wise anyway to take VD with Ca together, as there has been shown an inhibition of the cycle PTH---VD---(inorganic)Phosphorus---PTH (in either direction, the upregulating one as well as in the downregulating one).

My personal good experieince is:
  1. a sip of VD, then a sip of black tea (with caffeine downregulating VDR expression)
  2. doing 1. quite a while after having eaten something (phosphorus).
I guess, supplementation might be not as easy as one might think, "just throwing things in"!
 
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