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      Human Cytomegalovirus-Encoded microRNAs Can Be Found in Saliva Samples from Renal Transplant Recipients

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          Abstract

          Human cytomegalovirus (HCMV) infections are common following renal transplantation and may have long-lasting effects. HCMV can be measured directly by viral DNA or indirectly via host immune responses. HCMV-encoded microRNA (miRNA) may alter the pathobiology of HCMV infections and contribute to the progression of HCMV disease. HCMV-encoded miRNAs can be detected in blood but have not been sought in saliva. We investigated saliva samples from 32 renal transplant recipients (RTR) and 12 seropositive healthy controls for whom immunological data was available. Five HCMV-encoded miRNAs (miR-UL112-5p, miR-US5-2-3p, miR-UL36, miR-US25-2-3p and miR-UL22A) were sought using primer probe assays. HCMV miRNA species were detected in saliva from 15 RTR and 3 healthy controls, with miR-US5-2-3p most commonly detected. The presence of HCMV miRNAs associated with increased T-cell responses to HCMV IE-1 in RTR, suggesting a link with frequent reactivations of HCMV.

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          Most cited references28

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          Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA.

          Stress-inducible MICA, a distant homolog of major histocompatibility complex (MHC) class I, functions as an antigen for gammadelta T cells and is frequently expressed in epithelial tumors. A receptor for MICA was detected on most gammadelta T cells, CD8+ alphabeta T cells, and natural killer (NK) cells and was identified as NKG2D. Effector cells from all these subsets could be stimulated by ligation of NKG2D. Engagement of NKG2D activated cytolytic responses of gammadelta T cells and NK cells against transfectants and epithelial tumor cells expressing MICA. These results define an activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses.
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            Cytomegalovirus cell tropism.

            The human cytomegalovirus (HCMV) can infect a remarkably broad cell range within its host, including parenchymal cells and connective tissue cells of virtually any organ and various hematopoietic cell types. Epithelial cells, endothelial cells, fibroblasts and smooth muscle cells are the predominant targets for virus replication. The pathogenesis of acute HCMV infections is greatly influenced by this broad target cell range. Infection of epithelial cells presumably contributes to inter-host transmission. Infection of endothelial cells and hematopoietic cells facilitates systemic spread within the host. Infection of ubiquitous cell types such as fibroblasts and smooth muscle cells provides the platform for efficient proliferation of the virus. The tropism for endothelial cells, macrophages and dendritic cells varies greatly among different HCMV strains, mostly dependent on alterations within the UL128-131 gene locus. In line with the classification of the respective proteins as structural components of the viral envelope, interstrain differences concerning the infectivity in endothelial cells and macrophages are regulated on the level of viral entry.
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              Cytomegalovirus Infection and Relative Risk of Cardiovascular Disease (Ischemic Heart Disease, Stroke, and Cardiovascular Death): A Meta‐Analysis of Prospective Studies Up to 2016

              Background Several studies have suggested that cytomegalovirus infection is likely associated with an increased relative risk of cardiovascular disease (CVD); however, the results are inconsistent. We aimed to provide a systematic review and meta‐analysis of community‐based prospective studies assessing the association between cytomegalovirus infection and relative risk of CVD. Methods and Results We searched Medline and EMBASE to retrieve prospective studies that reported risk estimates of the association between cytomegalovirus infection and relative risk of CVD. The search yielded 10 articles including a total of 34 564 participants and 4789 CVD patients. Overall, exposure to cytomegalovirus infection was associated with a 22% (relative risk: 1.22, 95% CI: 1.07–1.38, P=0.002) increased relative risk of future CVD. We estimated that 13.4% of CVD incidence could be attributable to cytomegalovirus infection. Conclusions In conclusion, cytomegalovirus infection is associated with a significantly increased relative risk of CVD.
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                Author and article information

                Journal
                Noncoding RNA
                Noncoding RNA
                ncrna
                Non-Coding RNA
                MDPI
                2311-553X
                18 December 2020
                December 2020
                : 6
                : 4
                : 50
                Affiliations
                [1 ]School of Pharmacy & Biomedical Science, Curtin Health Innovation Research Institute, Curtin University, Perth 6102, Australia; shelley.waters@ 123456postgrad.curtin.edu.au (S.W.); k.munyard@ 123456exchange.curtin.edu.au (K.M.)
                [2 ]Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne 3004, Australia; bing.wang@ 123456baker.edu.au
                [3 ]Department of Microbiology, Pathwest Laboratory Medicine, Murdoch 6150, Australia; silvia.lee@ 123456curtin.edu.au
                [4 ]Renal Unit, Fiona Stanley Hospital, Murdoch 6150, Australia; ashley.irish@ 123456health.wa.gov.au
                Author notes
                Author information
                https://orcid.org/0000-0002-5113-8646
                https://orcid.org/0000-0002-9577-3764
                https://orcid.org/0000-0001-9580-2548
                Article
                ncrna-06-00050
                10.3390/ncrna6040050
                7768453
                33353107
                ee896aa7-3154-45c4-8159-81e5b4282f3c
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 November 2020
                : 16 December 2020
                Categories
                Communication

                cytomegalovirus,hcmv,kidney transplant,mirna,saliva
                cytomegalovirus, hcmv, kidney transplant, mirna, saliva

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