• Cytomegalovirus
• Entry mechanisms
• Glycoproteins
• Mucosal epithelial cells
• Neutralizing antibodies

• Humans
• Virus Internalization
• Cytomegalovirus/physiology
• Epithelial Cells/virology
• Antibodies, Neutralizing/immunology
• Cell Line
• Viral Envelope Proteins/metabolism
• Cytomegalovirus Infections/virology
• Palatine Tonsil/virology
• Palatine Tonsil/cytology
• Cells, Cultured
• Cell Differentiation
• Mucous Membrane/virology
• Antibodies, Viral/immunology

• R01 AI128912 NIAID NIH HHS
• R01 DE029471 NIDCR NIH HHS

• Allogeneic
• Cytomegalovirus
• Hematopoietic stem cell transplantation
• Infection

Immunosuppression by retroviruses including the human immunodeficiency virus—1 (HIV-1) is well known, however the mechanisms how retroviruses induce this immunosuppression is not fully investigated. It was shown that non-infectious retroviral particles as well as retroviral or recombinant retroviral transmembrane envelope (TM) proteins demonstrated immunosuppressive properties. The same was shown for peptides corresponding to a highly conserved domain in the TM protein. This domain is called immunosuppressive (ISU) domain and it induces modulation of the cytokine release of peripheral blood mononuclear cells (PBMCs) from healthy donors. In addition, it changes the gene expression of these cells. Common indications for the immunosuppressive activity were tumour growth in vivo and interleukin—10 (IL-10) release from human PBMCs in vitro. Single mutations in the ISU domain abrogated the immunosuppressive activity. In order to develop a new model system for the expression of the ISU domain and presentation to PBMCs which is not prone to possible endotoxin contaminations, two expression systems were developed. In the first system, designated pOUT, retroviral proteins containing the ISU domain were expressed and released into the cell culture medium, and in the second system, tANCHOR, the ISU domain was presented by a tetraspanin-anchored sequence on the cell surface of human cells. Both systems were exploited to express the wild-type (wt) ISU domains of HIV-1, of the porcine endogenous retrovirus (PERV) and of the murine leukaemia virus (MuLV) as well as to express mutants (mut) of these ISU domains. PERV is of special interest in the context of virus safety of xenotransplantation using pig organs. Expression of the TM proteins was demonstrated by confocal laser scanning microscopy, ELISA and Western blot analyses using specific antibodies. However, when cells expressing and releasing the ISU were co-incubated with human PBMCs, no increased production of IL-10 was observed when compared with the mutants. Similar results were obtained when the released TM proteins were concentrated by immunoprecipitation and added to PBMCs. We suggest that the absence of IL-10 induction can be explained by a low amount of protein, by the lack of a biologically active conformation or the absence of additional factors.

• Animals
• Coculture Techniques
• Gene Products, env/genetics
• Gene Products, env/immunology
• HEK293 Cells
• HeLa Cells
• Humans
• Immune Tolerance
• Interleukin-10/genetics
• Interleukin-10/immunology
• Leukocytes, Mononuclear/immunology
• Mice
• Mutation
• Protein Domains
• Swine

• Friede Springer Stiftung

• CMV
• HIV
• inflammation
• persistence
• reservoir

• furin cleavage
• gB genotypes
• glycoprotein B
• human cytomegalovirus
• selective pressure

• Aging
• CMV infection
• HIV infection
• Immune response
• Inflammation

• Cancer
• Cardiovascular diseases
• Elderly
• Human cytomegalovirus (CMV)
• Immunosenescence

During the last years increasing evidence implies that human cytomegalovirus (CMV) can be attributed to human malignancies arising from numerous tissues. In this perspective, we will review and discuss the potential mechanisms through which CMV infection may contribute to brain tumors by affecting tumor cell initiation, progression and metastasis formation. Recent evidence also suggests that anti-CMV treatment results in impaired tumor growth of CMV positive xenografts in animal models and potentially increased survival in CMV positive glioblastoma patients. Based on these observations and the high tumor promoting capacity of this virus, the classical and novel antiviral therapies against CMV should be revisited as they may represent a great promise for halting tumor progression and lower cancer deaths.

• Cytomegalovirus
• Oncovirus
• Glioblastoma
• Medulloblastoma
• Brain tumor

Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the long-term outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment.

This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated.

The mean duration of follow-up for the 72 patients was 43.16±19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state.

The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation.

• Colectomy
• Colitis
• Cytomegalovirus
• Ganciclovir
• ulcerative

Human cytomegalovirus (HCMV) infection is associated with cardiovascular disease (CVD) but the role of this virus in CVD progression remains unclear. We aimed to examine the HCMV serostatus in Russian patients (n = 90) who had undergone carotid endarterectomy (CEA) and controls (n = 82) as well as to determine the prevalence of HCMV immediate early (IE) and late (LA) antigens in carotid atherosclerotic plaques obtained from 89 patients. In addition, we sought to determine whether HCMV infection was associated with inflammatory activity in the plaque by quantifying infiltrating CD3 and CD68 positive cells and 5-LO immunoreactivity.

HCMV serology was assessed with ELISA and immunohistochemistry staining was performed to detect HCMV antigens, CD3, CD68 and 5-LO reactivity. The Fisher’s exact test was used to compare i) seroprevalence of HCMV IgG between patients and controls and ii) HCMV-positive or –negative to that of CD3, CD68 and 5-LO immunoreactive cells in plaque samples. The student-t test was performed to connote the significance level of mean optical density between patients and controls.

The seroprevalence for HCMV IgG was high in both patients and controls (99% and 98%, respectively). Controls had significantly higher IgG titers for HCMV compared with patients (p = 0.0148). Strikingly, we found a high prevalence of HCMV antigens in atherosclerotic plaques; 57/89 (64%) and 47/87 (54%) were HCMV IE and LA positive, respectively. Most plaques had rather low HCMV reactivity with distinct areas of HCMV-positive cells mainly detected in shoulder regions of the plaques, but also in the area adjacent to the necrotic core and fibrous cap. In plaques, the cellular targets for HCMV infection appeared to be mainly macrophages/foam cells and smooth muscle cells. HCMV-positive plaques trended to be associated with increased numbers of CD68 positive macrophages and CD3 positive T cells, while 5-LO reactivity was high in both HCMV-positive and HCMV-negative plaques.

In Russian patients undergoing CEA, HCMV proteins are abundantly expressed in carotid plaques and may contribute to the inflammatory response in plaques via enhanced infiltration of CD68 and CD3 cells.

• CMV pneumonia
• antiviral
• cytomegalovirus
• hematopoietic cell transplant
• prevention

Human cytomegalovirus (HCMV) is a ubiquitous DNA virus that can cause severe disease in immunosuppressive or immunocompromised patients. Recent studies have found that CMV might play a role in the pathogenesis and progression of inflammatory bowel disease (IBD). This paper gives a review of the epidemiology, clinical diagnosis, and pathogenesis of HCMV infection in patients with IBD.

• Inflammatory bowel disease
• Human cytomegalovirus
• Immunosuppression

Human cytomegalovirus (HCMV) is a herpesvirus that is prevalent in the human population. HCMV has recently been implicated in different cancer forms where it may provide mechanisms for oncogenic transformation, oncomodulation and tumour cell immune evasion. Moreover, antiviral treatment against HCMV has been shown to inhibit tumour growth in preclinical models. Here we describe the possible involvement of HCMV in cancer and discuss the potential molecular impact expression of HCMV proteins have on tumour cells and the surrounding tumour microenvironment.

• Cell Line
• Cytomegalovirus/metabolism
• Cytomegalovirus/pathogenicity
• Cytomegalovirus/physiology
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases/genetics
• DNA (Cytosine-5-)-Methyltransferases/metabolism
• DNA Methylation
• Fibroblasts/metabolism
• Gene Deletion
• HCT116 Cells
• Humans
• Virulence Factors/metabolism
• DNA Methyltransferase 3B

• Antiviral Agents/therapeutic use
• CD4-Positive T-Lymphocytes/physiology
• CD8-Positive T-Lymphocytes/physiology
• Cytomegalovirus/immunology
• Cytomegalovirus/pathogenicity
• Cytomegalovirus Infections/prevention & control
• Cytomegalovirus Infections/virology
• Cytomegalovirus Vaccines
• Humans
• Immunocompromised Host
• Viral Load

• Medical Research Council
• Wellcome Trust

• gliomas
• brain tumors
• viruses
• herpesviruses
• retroviruses
• oncomodulation
• progenitors
• stem cells

• Animals
• Brain Neoplasms/virology
• Cell Transformation, Viral/physiology
• Humans
• Neoplastic Stem Cells/virology
• Retroviridae/physiology
• Tumor Virus Infections/complications

• R01 CA134843 NCI NIH HHS
• R01 NS045209 NINDS NIH HHS

• R01 DK056328 NIDDK NIH HHS

• Adolescent
• Age of Onset
• Biliary Atresia/complications
• Biliary Atresia/mortality
• Biliary Atresia/surgery
• Child, Preschool
• Cytomegalovirus/isolation & purification
• Cytomegalovirus Infections/complications
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Liver Transplantation/mortality
• Liver Transplantation/statistics & numerical data
• Portoenterostomy, Hepatic/mortality
• Statistics, Nonparametric
• Treatment Outcome

Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA–protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein–Barr virus in the pathogenesis has been suggested. Similar to Epstein–Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1–70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus.

Sixty-one Mexican patients with systemic lupus erythematosus were tested for CMV and Epstein–Barr virus serology (viral capsid antigen, IgG, IgM) and autoantibodies by immunoprecipitation and ELISA (IgG and IgM class, U1RNP/Sm, U1–70 k, P peptide, rheumatoid factor, dsDNA, β₂-glycoprotein I).

IgG anti-CMV and IgM anti-CMV were positive in 95% (58/61) and 33% (20/61), respectively, and two cases were negative for both. Clinical manifestation and autoantibodies in the IgM anti-CMV(+) group (n = 20) versus the IgM anti-CMV(-)IgG (+) (n = 39) group were compared. Most (19/20) of the IgM anti-CMV(+) cases were IgG anti-CMV(+), consistent with reactivation or reinfection. IgM anti-CMV was unrelated to rheumatoid factor or IgM class autoantibodies and none was positive for IgM anti-Epstein–Barr virus–viral capsid antigen, indicating that this is not simply due to false positive results caused by rheumatoid factor or nonspecific binding by certain IgM. The IgM anti-CMV(+) group has significantly lower levels of IgG anti-U1RNP/Sm and IgG anti-U1–70 k (P = 0.0004 and P = 0.0046, respectively). This finding was also confirmed by immunoprecipitation. Among the IgM anti-CMV(-) subset, anti-Su was associated with anti-U1RNP and anti-Ro (P < 0.05). High levels of IgG anti-CMV were associated with production of lupus-related autoantibodies to RNA or DNA–protein complex (P = 0.0077).

Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs and may provide a unique insight to understand the pathogenesis.

• Animals
• Communicable Diseases/genetics
• Communicable Diseases/immunology
• Humans
• Immunity/genetics
• Immunity/immunology
• Immunity, Innate/genetics
• Immunity, Innate/immunology
• Infections/genetics
• Infections/immunology
• Lymphocytes/immunology
• Lymphocytes/metabolism
• Macrophages/immunology
• Macrophages/metabolism
• Mice
• Models, Immunological

• 15461-4 CIHR

• Computational Biology
• Cytomegalovirus/genetics
• Cytomegalovirus/immunology
• Epitopes, T-Lymphocyte/genetics
• Epitopes, T-Lymphocyte/immunology
• Genome, Viral
• Herpesviridae/genetics
• Herpesviridae/immunology
• Herpesvirus 1, Human/genetics
• Herpesvirus 1, Human/immunology
• Herpesvirus 4, Human/genetics
• Herpesvirus 4, Human/immunology
• Herpesvirus 8, Human/genetics
• Herpesvirus 8, Human/immunology
• Immediate-Early Proteins/immunology
• Rhadinovirus/genetics
• Rhadinovirus/immunology
• Viral Proteins/genetics
• Viral Proteins/immunology
• Virus Latency/immunology

• R01 AI061062 NIAID NIH HHS
• 1 R01 AI61062-01 NIAID NIH HHS

• Antibodies, Viral/blood
• Antigens, Viral/metabolism
• Cytomegalovirus/immunology
• Cytomegalovirus/isolation & purification
• Cytomegalovirus/metabolism
• Cytomegalovirus Infections/blood
• Cytomegalovirus Infections/complications
• Cytomegalovirus Infections/epidemiology
• Disease Progression
• Diverticulitis, Colonic/diagnosis
• Diverticulitis, Colonic/etiology
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Immediate-Early Proteins/metabolism
• Immunoglobulin G/blood
• Immunoglobulin M/blood
• Immunohistochemistry
• Male
• Prevalence

• Antigens, Viral/immunology
• Cytomegalovirus/immunology
• Cytomegalovirus Infections/blood
• Cytomegalovirus Infections/immunology
• Epitopes, T-Lymphocyte/immunology
• HLA-B Antigens/blood
• HLA-B Antigens/immunology
• HLA-B35 Antigen
• Humans
• Phosphoproteins/immunology
• Receptors, Antigen, T-Cell, alpha-beta/blood
• Receptors, Antigen, T-Cell, alpha-beta/immunology
• T-Lymphocytes/immunology
• Viral Matrix Proteins/immunology