Table of contents
Human cytomegalovirus infection downregulates vitamin-D receptor in mammalian cells - Jan 2017
The Journal of Steroid Biochemistry and Molecular Biology, Vol 165, Part B, Jan 2017, Pages 356–362, http://dx.doi.org/10.1016/j.jsbmb.2016.08.002
Franz J.J. Riedera, Charlotte Gröschelb, Marie-Theres Kastnera, Karin Kosulinc, Johannes Laengled, Rene Zadnikare, Rodrig Marculescue, Martina Schneidera, Thomas Lionc, f, Michael Bergmannd, Enikö Kallayb, Christoph Steiningera,
Highlights
•Vitamin D is essential for the human body including antimicrobial responses.
•Cytomegalovirus infection downregulates VDR expression in vitro..
•Expression of CYP24A1 decreases and of CYP27B1 increases in parallel.
•VDR expression is not downregulated during influenza virus or adenovirus replication.
•Cytomegalovirus may also influence VDR expression in vivo.
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 12 h [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 96 h. 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 12 h 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.
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Appears that many people have herpes and do not know it.
Herpes does not appear to lower the blood levels of vitamin D
Herpes appears to greatly restricts vitamin D getting to cells by downregulating the VDR
Cited by 17 studies as of Oct 2022
Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes - 2020
Nutrients 2020, 12(4), 962; https://doi.org/10.3390/nu12040962
by Choongho Lee. College of Pharmacy, Dongguk University, Goyang 10326, Korea
Vitamin D (VD) plays an essential role in mineral homeostasis and bone remodeling. A number of different VD-related genes (VDRG) are required for the metabolic activation of VD and the subsequent induction of its target genes. They include a set of genes that encode for VD-binding protein, metabolic enzymes, and the VD receptor. In addition to its well-characterized skeletal function, the immunoregulatory activities of VD and the related polymorphisms of VDRG have been reported and linked to its therapeutic and preventive actions for the control of several viral diseases. However, in regards to their roles in the progression of viral diseases, inconsistent and, in some cases, contradictory results also exist. To resolve this discrepancy, I conducted an extensive literature search by using relevant keywords on the PubMed website. Based on the volume of hit papers related to a certain viral infection, I summarized and compared the effects of VD and VDRG polymorphism on the infection, pathogenesis, and treatment outcomes of clinically important viral diseases. They include viral hepatitis, respiratory viral infections, acquired immunodeficiency syndrome (AIDS), and other viral diseases, which are caused by herpesviruses, dengue virus, rotavirus, and human papillomavirus. This review will provide the most current information on the nutritional and clinical utilization of VD and VDRG in the management of the key viral diseases. This information should be valuable not only to nutritionists but also to clinicians who wish to provide evidence-based recommendations on the use of VD to virally infected patients.
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Human Cytomegalovirus protects itself by down-regulating the VDR (not clear by how much) - Sept 2022
Human Cytomegalovirus Induces Vitamin-D Resistance In Vitro by Dysregulating the Transcriptional Repressor Snail
Viruses 2022, 14(9), 2004; https://doi.org/10.3390/v14092004
Carmen Stecher., Katharina Philomena Maurer
Vitamin-D supplementation is considered to play a beneficial role against multiple viruses due to its immune-regulating and direct antimicrobial effects. In contrast, the human cytomegalovirus (HCMV) has shown to be resistant to treatment with vitamin D in vitro by downregulation of the vitamin-D receptor. In this study, we aimed to elucidate the mechanism and possible biological consequences of vitamin-D resistance during HCMV infection. Mechanistically, HCMV induced vitamin-D resistance by downregulating the vitamin-D receptor (VDR) within hours of lytic infection. We found that the VDR was inhibited at the promoter level, and treatment with histone deacetylase inhibitors could restore VDR expression. VDR downregulation highly correlated with the upregulation of the transcriptional repressor Snail1, a mechanism likely contributing to the epigenetic inactivation of the VDR promoter, since siRNA-mediated knockdown of Snail partly restored levels of VDR expression. Finally, we found that direct addition of the vitamin-D-inducible antimicrobial peptide LL-37 strongly and significantly reduced viral titers in infected fibroblasts, highlighting VDR biological relevance and the potential of vitamin-D-inducible peptides for the antiviral treatment of vitamin-D deficient patients
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See also web
- https://en.wikipedia.org/wiki/Epidemiology_of_herpes_simplex WikiPedia 2016
"About 1 in 5 Americans (16.2%) aged 14 to 49 is infected with HSV-2. HSV-2 prevalence was nearly twice as high among women (20.9%) than men (11.5%), and was more than three times higher among blacks (39.2%) than non-Hispanic whites (12.3%). The most affected group was black women, with a prevalence rate of 48%."
"Although many people infected with HSV develop labial or genital lesions (herpes simplex), the majority are either undiagnosed or display no physical symptoms—individuals with no symptoms are described as asymptomatic or as having subclinical herpes." - Herpes Zoster Rates Are Increasing, but Why? Medscape 2014
" In the United States, herpes zoster rates have increased by 39% from 1992 to 2010 among adults older than 65 years of age"