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      The Detection of CMV in Saliva Can Mark a Systemic Infection with CMV in Renal Transplant Recipients

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          Abstract

          Human cytomegalovirus (CMV) is often transmitted through saliva. The salivary gland is a site of CMV replication and saliva can be used to diagnose congenital CMV infections. CMV replication is monitored in whole blood or plasma in renal transplant recipients (RTR) and associates with clinical disease. However, these assays may not detect replication in the salivary gland and there is little data linking detection in saliva with systemic infection and clinical sequelae. RTR ( n = 82) were recruited > 2 years after transplantation. An in-house quantitative PCR assay was used to detect CMV UL54 in saliva samples. CMV DNA was sought in plasma using a commercial assay. Vascular health was predicted using flow mediated dilatation (FMD) and plasma biomarkers. CMV-reactive antibodies were quantified by ELISA and circulating CMV-specific T-cells by an interferon-γ ELISpot assay. Vδ2 γδ T-cells were detected using multicolor flow cytometry reflecting population expansion after CMV infection. The presence of CMV DNA in saliva and plasma associated with plasma levels of antibodies reactive with CMV gB and with populations of circulating Vδ2 γδ T -cells ( p < 0.01). T-cells reactive to CMV immediate early (IE)-1 protein were generally lower in patients with CMV DNA in saliva or plasma, but the level of significance varied ( p = 0.02–0.16). Additionally, CMV DNA in saliva or plasma associated weakly with impaired FMD ( p = 0.06–0.09). The data suggest that CMV detected in saliva reflects systemic infections in adult RTR.

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          Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and meta-analysis

          Cytomegalovirus (CMV) infection does not usually produce symptoms when it causes primary infection, reinfection, or reactivation because these three types of infection are all controlled by the normal immune system. However, CMV becomes an important pathogen in individuals whose immune system is immature or compromised, such as the unborn child. Several vaccines against CMV are currently in clinical trials that aim to induce immunity in seronegative individuals and/or to boost the immunity of those with prior natural infection (seropositives). To facilitate estimation of the burden of disease and the need for vaccines that induce de novo immune responses or that boost pre-existing immunity to CMV, we conducted a systematic survey of the published literature to describe the global seroprevalence of CMV IgG antibodies. We estimated a global CMV seroprevalence of 83% (95%UI: 78-88) in the general population, 86% (95%UI: 83-89) in women of childbearing age, and 86% (95%UI: 82-89) in donors of blood or organs. For each of these three groups, the highest seroprevalence was seen in the World Health Organisation (WHO) Eastern Mediterranean region 90% (95%UI: 85-94) and the lowest in WHO European region 66% (95%UI: 56-74). These estimates of the worldwide CMV distribution will help develop national and regional burden of disease models and inform future vaccine development efforts.
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            Cytomegalovirus in solid organ transplant recipients—Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice

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              Long-term expansion of effector/memory Vdelta2-gammadelta T cells is a specific blood signature of CMV infection.

              The ability of human gammadelta T cells to develop immunologic memory is still a matter of debate. We previously demonstrated the involvement of Vdelta2- gammadelta T lymphocytes in the response of immunosuppressed organ recipients to cytomegalovirus (CMV). Here, we demonstrate their ability to mount an adaptive immune response to CMV in immunocompetent subjects. Vdelta2- gammadelta T-cell peripheral blood numbers, repertoire restriction, and cytotoxicity against CMV-infected fibroblasts were markedly increased in CMV-seropositive, compared with CMV-seronegative, healthy persons. Whereas Vdelta2- gammadelta T cells were found as naive cells in CMV- patients, they virtually all exhibited the cytotoxic effector/memory phenotype in CMV+ patients, which is also observed in transplanted patients challenged with CMV. This long-term complete remodeling of the Vdelta2- gammadelta T-cell population by CMV predicts their ability to exhibit an adaptive anti-CMV immune response. Consistent with this, we observed that the secondary response to CMV was associated with a faster gammadelta T-cell expansion and a better resolution of infection than the primary response. In conclusion, the increased level of effector-memory Vdelta2- gammadelta T cells in the peripheral blood is a specific signature of an adaptive immune response to CMV infection of both immunocompetent and immunosuppressed patients.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                22 October 2019
                October 2019
                : 20
                : 20
                : 5230
                Affiliations
                [1 ]School of Biomedical Science, Curtin University, Bentley 6102, Australia; shelley.waters@ 123456postgrad.curtin.edu.au (S.W.); silvia.lee@ 123456curtin.edu.au (S.L.)
                [2 ]Department of Microbiology and Infectious Diseases, Pathwest Laboratory Medicine, Murdoch 6150, Australia
                [3 ]School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Australia; megan.lloyd@ 123456uwa.edu.au
                [4 ]School of Biomedical Sciences, University of Western Australia, Nedlands 6009, Australia
                [5 ]Renal Unit, Fiona Stanley Hospital, Murdoch 6150, Australia; Ashley.Irish@ 123456health.wa.gov.au
                [6 ]School of Medicine and Pharmacology, University of Western Australia, Nedlands 6009, Australia
                Author notes
                [* ]Correspondence: patricia.price@ 123456curtin.edu.au ; Tel.: +61-8-9266-9716
                Author information
                https://orcid.org/0000-0002-9577-3764
                Article
                ijms-20-05230
                10.3390/ijms20205230
                6829882
                31652514
                cfe2da20-ef0d-4928-ae18-1592f8aac4f5
                © 2019 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
                : 03 September 2019
                : 18 October 2019
                Categories
                Article

                Molecular biology
                cytomegalovirus infection,saliva,renal transplantation
                Molecular biology
                cytomegalovirus infection, saliva, renal transplantation

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