Have been documenting an international series of infectious-like events in which deaths and medical admissions simultaneously rise in what can be best described as a rectangular wave effect. Have written a review attempting to link CMV to these suspected outbreaks. Any thoughts or suggestions would be welcome along with potential research which could be relevant. Many thanks for your valuable time. Kind Regards Rod
P.S. even if CMV is not the direct agent I would be highly surprised if it were not taking opportunistic advantage as it does in HIV/AIDS
Hi Rodney,
Please find beneath newly interdisciplinary approach to the molecular mechanisms of transcriptional activarion of cytomrgalovirus (and some other common human viruses) by bodily amounts of dioxins, the most potential xenobiotics so far known, that facilitate cytomegalovirus-mediated inflammation and malignization pathways.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 2012 Volume 16, Supplement 1, Page e115-119
TITLE: Xenobiotical virology: novel mechanistic concept of hazardous human viruses upregulation by body burden level of dioxins via AhR-mediated transcriptional pathway
Ilya Tsyrlov, I. Shur, D. Oshchepkov, A. Pokrovsky
ABSTRACT
Background: Earlier we discovered transactivation of the HIV-1 and hepatitis B virus (HBV) in human cells by 30-300 ppt dioxin, a xenobiotic with extremely long serum half-life in humans. Also, upregulation of cytomegalovirus (HCMV) in human cells was shown by 10 ppq dioxin whereas current its background level in general population is ∼4 ppt. So, human viruses were suggested novel target genes of cellular dioxin receptor (AhR/Arnt) complex. The complex was known as binding to dioxin-responsive elements (DRE) within mammalian genes, and amount of DREs determine level of target gene activation.
Methods: Productions of infectious HIV-1 in MT4 cells, HCMV in THP-1 cells, and HBV in HepG2 cells were determined using plaque assay. Viral DNAs were determined by hybridization and PCR. A computational search for viral DRE was performed by SITECON, a tool for detecting transcription factor binding site alignments/site recognition.
Results: A total of 13 bona fide DRE, all including the substitution intolerant core sequence (5’-GCGTG-3’) and SITECON-selected adjacent variable sequences were used here to detect the above properties for the DRE site, and conformational similarity score threshold of 0.95 was utilized to rank identified DRE. It was found that regulatory region of HCMV genes encoding IE gp/UL37 has 5 DRE, 1.65 kb/UL36 – 6 DRE, pp65 – 7 DRE, pp71 – 7 DRE, and pp150 –10 DRE. Wile juxtaposing DRE contents with experimental results, the most susceptible candidate virus to be augmented with body burden dioxin is that one possessing at least similar to HCMV amount of DRE. SITECON recognized several cancer-associated human viruses possessing multiple DREs in their promoters. Thus Epstein-Barr virus (EBV) promoters L1A and L1 each contain 16 DRE, and gene of EBV R1 145K - 11 DRE. Genes encoding some major proteins of herpes simplex virus (HSV) type 1 have from 7 to 8 promoter DRE.
Conclusion: The above support the concept, and provide evidence that sub-nanomolar dioxin is able to activate DRE-containing viruses. Mechanistic data obtained allow searching for inhibitors of viremia and virally-driven malignancies among antagonist ligands of cytosolic Ah receptor, and modifiers of AhR/Arnt complex binding to viral DRE.
Best wishes,
Ilya
Dear Ilya, Many thanks. CMV is a remarkable pathogen, we are only beginning to scratch the surface. Rod
I agree Rodney,
Lets "scratch" the CMV' mechanisms of pathogenicity together.
Ilya
The CMV screening is important before bone marrow graft and liver graft or transplantation. It is also important for women antenatal survey.
About pregancy and transplantation you can see:
I think that this link may be useful for you.
Pathogenesis of human cytomegalovirus infection and ...
www.sciencedirect.com/.../pii/S019888590400045X
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de G Gerna - 2004 - Cité 93 fois - Autres articles
In acquired immunodeficiency syndrome patients with human cytomegalovirus (HCMV), disseminated infection, and end-organ disease, autopsy findings show ...
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