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  • Cytomegalovirus Infections
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  • 1
    Language: English
    In: Medical Microbiology and Immunology, 2011, Vol.200(1), pp.1-5
    Description: The question whether human cytomegalovirus may affect cancer diseases has been discussed (very controversially) for decades. There are convinced believers and strict opponents of the idea that HCMV might be able to play a role in the course of cancer diseases. In parallel, the number of published reports on the topic is growing. Recently published and presented (Ranganathan P, Clark P, Kuo JS, Salamat S, Kalejta RF. A Survey of Human Cytomegalovirus Genomic Loci Present in Glioblastoma Multiforme Tissue Samples. 35th Annual International Herpes Workshop, Salt Lake City, 2010) data on HCMV detection in glioblastoma tissues and colocalisation of HCMV proteins with cellular proteins known to be relevant for glioblastoma progression motivated us to recapitulate the current state of evidence.
    Keywords: Cytomegalovirus ; Cancer ; Oncomodulation ; Tumour virus ; Glioblastoma ; Neuroblastoma
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 2
    Language: English
    In: Medical Microbiology and Immunology, 2010, Vol.199(1), pp.53-60
    Description: Since the dynamics of transmission of human cytomegalovirus (HCMV) have not been clarified yet, we assessed a possible change in HCMV seroprevalence in Frankfurt am Main, Germany during the past twenty years and tried to detect variables with an impact on epidemiology. Between 1/1/1988 and 10/15/2008, a total of 54443 serum samples were collected for routine diagnostics and analyzed using Enzygnost Anti HCMV-IgG enzyme immunoassay (Siemens/Dade Behring, Marburg, Germany). Two decades, 1/1/1988–12/31/1997 and 1/1/1998–10/15/2008, and several groups (type of health insurance, gender, age, HIV-status) were evaluated to assess changes in seroprevalence. Regarding both decades, the overall age-adjusted prevalence of HIV-negative patients dropped from 63.70% (confidence interval (CI) 95% 63.15–64.25) to 57.25% (CI 95% 56.57–57.93; P  〈 0.0001). Private health insurance (PHI) patients showed significant lower HCMV seroprevalences than members of obligatory health insurances (OHI) in both decades (1988–1997: PHI = 55.79%, OHI = 64.27%; P  〈 0.0001; 1998–1908: PHI = 47.02%, OHI = 58.74%; P  〈 0.0001). Furthermore, comparing the two decades, there was generally a gender-specific statistically significant decrease in HCMV seroprevalence for males (63.54–55.54%) and females (63.83–58.73%) as well as for members of PHI and OHI (PHI males: 57.59% to 47.19%, PHI females 54.10–46.80%; OHI males: 64.00–57.06%, OHI females 64.50–60.11%). Also, while female HIV-positive patients showed significant difference in HCMV seroprevalence between the two decades (83.17 and 87.80%, P  = 0.023), there was no significant difference in male patients with HIV (88.76 and 87.32% in the first and second decade, respectively ( P  = 0.196). The cumulative HCMV prevalence of all HIV-negative patients tested in the past 20 years demonstrates a biphasic, age-related rise of HCMV seroprevalence throughout all age-groups. The seroprevalence of HCMV has declined between 1988–1997 and 1998–2008 in Frankfurt am Main, Germany. The decline varied between different age-groups. HCMV prevalence correlates with the type of health insurance, gender, age, and HIV-status.
    Keywords: Cytomegalovirus ; Seroepidemiology ; HCMV ; Germany ; Prevalence
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 3
    Language: English
    In: Journal of Clinical Virology, 2011, Vol.51(4), pp.285-288
    Description: Human cytomegalovirus (CMV) is considered as the most common cause of congenital infection in humans and the overall burden for the public health system is rather high. About 1/10 of vertically infected newborns present or develop severe signs of cytomegalic inclusion disease (CID), with the classical triad of chorioretinitis, microcephaly and cerebral calcifications. However the most symptomatic cases are detected postnatal and methods of diagnostic virology raised the questions for the gold standard in laboratory screening. The current problems in diagnosis and therapy are outlined in two different cases: An acute primary CMV infection with no clinical signs of illness in both mother and child and a secondary CMV-infection resulting in necrotizing CMV encephalitis in the fetus. Beside virus detection in whole blood samples and other fluids, newly adopted laboratory assays like the destination of CMV-IgG avidity were necessary. Furthermore a serologic screening for pregnant women should be implicated routinely. Passive IgG treatment of the mother was helpful but the ultimate goal in prevention of congenital CMV infection is to develop a vaccine, which would be administered to seronegative women.
    Keywords: Primary Infection ; Reactivation ; Secondary Infection ; Pregnancy ; Ventriculomegaly ; Ascites ; Biology
    ISSN: 1386-6532
    E-ISSN: 1873-5967
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  • 4
    Language: English
    In: Medical Microbiology and Immunology, 2013, Vol.202(1), pp.37-47
    Description: Although several host factors have been identified to influence the course of HCMV infection, it still remains unclear why in AIDS patients without highly active antiretroviral therapy human cytomegalovirus (HCMV) retinitis is one of the most common opportunistic infections, whereas in other immunosuppressed individuals it has a low incidence. It was suggested that HCMV glycoprotein B strains may be suitable as marker for virulence and HCMV retinitis. Moreover, UL144 ORF, a member of the TNF-α receptor superfamily, may play a crucial role in innate defences and adaptive immune response of HCMV infection. Furthermore, sequence analyses of HCMV genes UL128, UL130, and UL131A as major determinants of virus entry and replication in epithelial and other cell types were performed. To evaluate the association of sequence variability of depicted viral genes with HCMV retinitis and in vitro growth properties in retinal pigment epithelial cells (RPE) and human foreskin fibroblasts (HFF), we compared 14 HCMV isolates obtained from vitreous fluid and urine of AIDS patients with clinically proven HCMV retinitis. Isolates were analyzed by PCR cycle sequencing and phylogenetic analysis. In addition, sequences of HCMV strains AF1, U8, U11, VR1814, and its cell culture adapted derivates were included. Sequence analysis of gB yielded three genetic subtypes (gB type 1 (5 isolates), gB type 2 (12 isolates), and gB type 3 (5 Isolates)), whereas sequence analysis of UL144 showed a greater diversity (7 isolates type 1A, 2 isolates type 1C, 7 isolates type 2, and 3 isolates type 3). In contrast, the UL128, UL130, and UL131A genes of all low-passage isolates were highly conserved and showed no preferential clustering. Moreover, in HFF and RPE cells, all of our HCMV isolates replicated efficiently independently of their genetic subtype. In conclusion, beside a possible link between the gB subtype 2 and HCMV retinitis, our study found no direct evidence for a connection between UL144/UL128/UL130/UL131A genotypes and the incidence of HCMV retinitis in AIDS patients.
    Keywords: Cytomegalovirus ; Viral tropism and virulence ; Retinitis ; AIDS
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 5
    Language: English
    In: Medical Microbiology and Immunology, 2009, Vol.198(2), pp.79-81
    Description: The (possible) relationship between HCMV and cancer has been discussed for decades. Detection of viral DNA, mRNA and/or antigens in tumour tissues as well as seroepidemiologic evidence suggested a role of HCMV infection in several human malignancies. However, controversial clinical results from diVerent groups had raised skepticism about a role of HCMV in cancer.
    Keywords: Cytomegalovirus–Physiology ; Cytomegalovirus Infections–Complications ; Humans–Etiology ; Neoplasms–Virology ; Neoplasms–Virology ; Infections ; Viruses ; Cancer ; Pathology;
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 6
    Language: English
    In: Medical Microbiology and Immunology, 2009, Vol.198(4), pp.257-262
    Description: A coupled luminescent method (CLM) based on glyceraldehyde-3-phosphate dehydrogenase released from injured target cells was used to evaluate the cytotoxicity of antigen-specific HLA class I-restricted CTLs. In contrast to established methods, CLM does not require the pretreatment of target cells with radioactive or toxic labeling substances. CTLs from healthy HLA-A2 positive donors were stimulated by autologous dendritic cells (DCs) pulsed with HLA-A2 restricted HCMV-pp65 nonamer peptides. HLA-A2 positive T2 cells or autologous monocytes pulsed with HCMV-pp65 nonamer peptide served as target cells. Lysis was detected only in HCMV-pp65-pulsed target cells incubated with CTLs from seropositive donors stimulated by HCMV-pp65-pulsed DCs. After 3 days, stimulation 38% of T2 cells and 17% of monocytes were lysed at an effector to target ratio of 8:1. In conclusion, CLM represents a highly sensitive, fast, material-saving and non-toxic/non-radioactive method for the measurement of antigen-specific CTL cytotoxic activity.
    Keywords: Cytotoxic T lymphocytes ; HLA-A2-restricted peptide ; Human cytomegalovirus ; Cytotoxicity ; Coupled luminescent method ; Dendritic cells
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 7
    Language: English
    In: Journal of Immunological Methods, 2006, Vol.311(1), pp.164-173
    Description: The detection and quantification of specific T lymphocytes against human cytomegalovirus (HCMV) has proven an important laboratory marker in the monitoring of patients after stem cell transplantation (SCT). In these patients HCMV infections may cause severe disease and death. However, the determination of HCMV-specific T lymphocytes may be limited by lymphopenia occurring after transplantation. We evaluated a commercial test kit for the reliable determination of HCMV-specific T lymphocyte development in lymphopenic patients after stem cell transplantation. Using a whole blood protocol for the flow cytometric detection of antigen-specific CD4 T-helper and CD8 cytotoxic T lymphocytes this test kit measures intracellular cytokine production after stimulation with HCMV antigen. The measurement of HCMV-specific T lymphocytes was feasible when at least 3000 CD4 or 1000 CD8 T cells could be counted by flow cytometry. Detection of HCMV-specific T lymphocytes was possible, on average, 67 (SD ± 61) days after transplantation for CD4 cells and 27 (SD ± 13) days for CD8 cells, thus being still within the critical time for HCMV reactivation. In conclusion, the use of modern test kits permits the measurement of HCMV-specific T lymphocytes in stem cell transplant recipients and may be included in the HCMV monitoring system after SCT.
    Keywords: Flow Cytometric Analysis ; Antigen-Specific T Lymphocytes ; Intracellular Cytokine Expression ; Stem Cell Transplantation ; Human Cytomegalovirus ; Medicine ; Biology
    ISSN: 0022-1759
    E-ISSN: 1872-7905
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  • 8
    Language: English
    In: Trends in Molecular Medicine, 2004, Vol.10(1), pp.19-23
    Description: Recently, the term oncomodulation has been proposed to express the ability of human cytomegalovirus (HCMV) to modify tumor cell biology, a phenomenon that is independent from transformation. Because past studies have failed to show that HCMV can transform normal human cells, HCMV has not been regarded as an oncogenic tumor virus. However, recent investigations have revealed a high frequency of HCMV in tumor cells of malignancies such as colon cancer, malignant glioma, prostatic intraepithelial neoplasia, and carcinoma. Data from experiments with HCMV-infected tumor cell lines have highlighted the oncomodulatory potential of HCMV and provided important insights into the patho- mechanisms associated with aberrant signaling pathways and transcription factor and/or tumor suppressor function of the host cell.
    Keywords: Medicine ; Biology
    ISSN: 1471-4914
    E-ISSN: 1471-499X
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  • 9
    Language: English
    In: Medical Microbiology and Immunology, 2004, Vol.193(4), pp.205-208
    Description: The underlying mechanisms leading to persistence of human cytomegalovirus (HCMV) in the immune privileged retina are not fully understood. This in vitro study was done to evaluate the influence of HCMV-infected retinal glial cells on epithelial barrier functions. Glial cells derived from human eyes were cultured and infected with the clinical HCMV isolate Hi91. Supernatants of mock (GS mock ) and Hi91 (GS Hi91 ) -infected glial cells were collected at 72 h post inoculation and used for incubation of CaCo-2 cells grown in transwell chambers. Transepithelial electrical resistance (TER) was analyzed as a measure of epithelial integrity. Virus-free GS Hi91 but not GS mock increased TER from 250 Ω/cm 2 to more than 1,000 Ω/cm 2 within 2 h. Increased TER values were measured up to 48 h ( n =3). No changes in TER were observed when conditioned supernatants from HCMV-infected human foreskin fibroblasts were used. No evidence of GS Hi91 -induced modification of β-catenin (zonula adherens) or occludin and ZO-1 (zonula occludens) was found. Our results suggest that HCMV-infected glial cells may support epithelial barrier functions by a yet unknown mechanism. Our findings may help to explain the ocular persistence of HCMV and the maintenance of ocular immune privilege early in infection.
    Keywords: Human cytomegalovirus ; Immune privilege ; Junction molecules ; Retinitis
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 10
    Language: English
    In: Journal of Clinical Virology, 2006, Vol.35(2), pp.160-166
    Description: The human cytomegalovirus (HCMV) causes severe complications in immunosuppressed patients, resulting in increased morbidity and mortality. The immunological components important for the control of HCMV are still not completely understood. To evaluate the importance of cellular and humoral immunity in stem cell transplant (SCT) recipients, we analysed levels of HCMV specific IFN-γ producing CD4 cells and glycoprotein B (gB) specific antibodies in HCMV positive SCT patients with and without reactivation episodes after SCT. Patients without HCMV reactivation episodes showed a slow but steady increase in both parameters after SCT, indicating that initial high levels of gB specific antibodies or HCMV specific CD4 IFN-γ+ cells are not necessary to prevent reactivation of HCMV. In contrast, patients with reactivation episodes showed a steep, significant increase in HCMV specific CD4 IFN-γ+ counts just prior to HCMV reactivation, followed by a decline after the reactivation period. Patients who underwent only a single reactivation generated significant higher amounts of CD4 IFN-γ+ cells, than did patients with further reactivation episodes. The course of gB specific antibodies for reactivating patients was different, with significantly higher average values in the patients with HCMV reactivation. This indicates that patients with a HCMV reactivation exhibit a stronger humoral dominated immune response.
    Keywords: Human Cytomegalovirus (Hcmv) ; Hcmv Specific Cd4 + IFN-Γ+ Cells ; Glycoprotein B (Gb) Specific Antibodies ; Stem Cell Transplant Recipients ; Biology
    ISSN: 1386-6532
    E-ISSN: 1873-5967
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