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Sample records for active cytomegalovirus infections

  1. Cytomegalovirus infection in inflammatory bowel disease is not associated with worsening of intestinal inflammatory activity.

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    Alexandre Medeiros do Carmo

    Full Text Available Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus.Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations.Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient.Among the 400 eligible patients, 249 had Crohn's disease, and 151 had ulcerative colitis. In the group of Crohn's disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine.The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV and inflammatory bowel

  2. Cytomegalovirus infection in transplant recipients

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    Azevedo*, Luiz Sergio; Pierrotti, Lígia Camera; Abdala, Edson; Costa, Silvia Figueiredo; Strabelli, Tânia Mara Varejão; Campos, Silvia Vidal; Ramos, Jéssica Fernandes; Latif, Acram Zahredine Abdul; Litvinov, Nadia; Maluf, Natalya Zaidan; Filho, Helio Hehl Caiaffa; Pannuti, Claudio Sergio; Lopes, Marta Heloisa; dos Santos, Vera Aparecida; da Cruz Gouveia Linardi, Camila; Yasuda, Maria Aparecida Shikanai; de Sousa Marques, Heloisa Helena

    2015-01-01

    Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia. PMID:26222822

  3. Cytomegalovirus infection in transplant recipients

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    Luiz Sergio Azevedo

    2015-07-01

    Full Text Available Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease. The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia.

  4. Cytomegalovirus infection with lissencephaly

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    Joseph Leena

    2008-07-01

    Full Text Available Lissencephaly is a malformation of the brain in which the brain surface is smooth, rather than convoluted. Among the various causes of lissencephaly, infection by a virus during pregnancy plays an important role. Cytomegalovirus (CMV is an important pathogen causing this anomaly. We present this case of a young female with 24-week-gestation diagnosed on ultrasound as carrying an anomalous fetus with lissencephalic features. At autopsy, there were multiple intra-nuclear CMV inclusions in the brain and the kidneys. This case is presented for its rarity and for the documentation of the tissue localization of CMV inclusions at autopsy.

  5. Peripheral Blood Leukocytes and Serum Nested Polymerase Chain Reaction Are Complementary Methods for Monitoring Active Cytomegalovirus Infection in Transplant Patients

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    PD Andrade

    2013-01-01

    Full Text Available BACKGROUND: Human cytomegalovirus is an important cause of morbidity and mortality in immunocompromised patients. Qualitative polymerase chain reaction (PCR has proven to be a sensitive and effective technique in defining active cytomegalovirus infection, in addition to having low cost and being a useful test for situations in which there is no need for quantification. Real-time PCR has the advantage of quantification; however, the high cost of this methodology makes it impractical for routine use.

  6. Cytomegalovirus Infection of the Rat Developing Brain In Utero Prominently Targets Immune Cells and Promotes Early Microglial Activation

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    Cloarec, Robin; Bauer, Sylvian; Luche, Hervé; Buhler, Emmanuelle; Pallesi-Pocachard, Emilie; Salmi, Manal; Courtens, Sandra; Massacrier, Annick; Grenot, Pierre; Teissier, Natacha; Watrin, Françoise; Schaller, Fabienne; Adle-Biassette, Homa; Gressens, Pierre; Malissen, Marie; Stamminger, Thomas; Streblow, Daniel N.; Bruneau, Nadine; Szepetowski, Pierre

    2016-01-01

    Background Congenital cytomegalovirus infections are a leading cause of neurodevelopmental disorders in human and represent a major health care and socio-economical burden. In contrast with this medical importance, the pathophysiological events remain poorly known. Murine models of brain cytomegalovirus infection, mostly neonatal, have brought recent insights into the possible pathogenesis, with convergent evidence for the alteration and possible involvement of brain immune cells. Objectives and Methods In order to confirm and expand those findings, particularly concerning the early developmental stages following infection of the fetal brain, we have created a model of in utero cytomegalovirus infection in the developing rat brain. Rat cytomegalovirus was injected intraventricularly at embryonic day 15 (E15) and the brains analyzed at various stages until the first postnatal day, using a combination of gene expression analysis, immunohistochemistry and multicolor flow cytometry experiments. Results Rat cytomegalovirus infection was increasingly seen in various brain areas including the choroid plexi and the ventricular and subventricular areas and was prominently detected in CD45low/int, CD11b+ microglial cells, in CD45high, CD11b+ cells of the myeloid lineage including macrophages, and in CD45+, CD11b– lymphocytes and non-B non-T cells. In parallel, rat cytomegalovirus infection of the developing rat brain rapidly triggered a cascade of pathophysiological events comprising: chemokines upregulation, including CCL2-4, 7 and 12; infiltration by peripheral cells including B-cells and monocytes at E17 and P1, and T-cells at P1; and microglia activation at E17 and P1. Conclusion In line with previous findings in neonatal murine models and in human specimen, our study further suggests that neuroimmune alterations might play critical roles in the early stages following cytomegalovirus infection of the brain in utero. Further studies are now needed to determine which

  7. Kinetics of US28 gene expression during active human cytomegalovirus infection in lung-transplant recipients

    NARCIS (Netherlands)

    Boomker, JM; Verschuuren, EAM; Brinker, MGL; de Leij, LFMH; The, TH; Harmsen, MC

    2006-01-01

    Targeting viral proteins early during infection may limit exacerbation of human cytomegalovirus infection. The viral chemokine-receptor homologue US28 interferes with leukocyte trafficking and, possibly, viral replication. Because US28 molecules are abundant on the surface of infected cells, this ho

  8. Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

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    Juteau Jean-Marc

    2009-12-01

    Full Text Available Abstract Background Phosphorothioated oligonucleotides (PS-ONs have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV infections in vitro and in vivo was therefore investigated. Results In vitro, a 40 mer degenerate AP (REP 9 inhibited both murine CMV (MCMV and guinea pig CMV (GPCMV with an IC50 of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C inhibited MCMV with an IC50 of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism in vivo. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers. Conclusion These studies indicate that APs exhibit potent, well tolerated

  9. Cytomegalovirus infection in infertile women

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    May Yossif Saour

    2011-08-01

    Full Text Available Objective: Cytomegalovirus (CMV is a virus that can be transmitted to a developing child before birth. For most healthy persons who acquire CMV after birth, there are few symptoms. Once a person becomes infected, the virus remains alive, but usually dormant within that person’s body for life. There are two different types of infection: primary CMV and recurrent CMV infection. Primary infection can cause more serious problems in pregnancy than recurrent infection can. However, if a person's immune system is seriously weakened in any way, the virus can become active and cause CMV disease. The aim of this study is to evaluate CMV infection, antisperm antibodies in infertile women and its relation to other parameters. Method: Fifty infertile women who presented at the Infertility Clinic of Kammal Al-Sammaree Hospital from May 2008 to July 2009 and thirty fertile control group were included in this study. CMV IgG and IgM measurements were performed by ELISA and antisperm antibody was measured by immunofluorescence test. High vaginal and cervical swabs taken for wet mount, Gram stain and culture. Results: There was no significant difference between infertile and control group regarding CMV IgG. The presence of CMV IgG in the serum was significantly related with previous genital infection of infertility (p<0.001 and previous abortion (p=0.032. Seropositive CMV IgG did not reflect a significant relation with leukocytes number, type of bacteria and antisperm antibody. Conclusion: CMV IgG was detected in infertile women and had no significant relation with antisperm antibodies and other parameters. [J Exp Integr Med 2011; 1(4.000: 273-276

  10. Latent cytomegalovirus infection exacerbates experimental pulmonary fibrosis by activating TGF-β1.

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    Li, Yonghuai; Gao, Jian; Wang, Guoliang; Fei, Guanghe

    2016-08-01

    The aim of the present study was to investigate the hypotheses that cytomegalovirus (CMV) may trigger idiopathic pulmonary fibrosis (IPF) in a susceptible host and/or that the presence of CMV may alter IPF in response to a well-defined trigger of pulmonary fibrosis. A mouse model of murine CMV (MCMV) infection was established, and the mice were divided into a control group, bleomycin group and an MCMV+bleomycin group. Changes in the weights of the mice were determined in the three groups. Pulmonary fibrosis was detected using a histopathological method. The activity of transforming growth factor (TGF)‑β1 was measured, and the levels of E‑cadherin, Vimentin and phosphorylated (phospho)‑small mothers against decapentaplegic (SMAD)2 were determined using western blot analysis. MCMV was found to invade the lungs, however, it did not cause pulmonary fibrosis. The progression of fibrosis in the mice treated with MCMV+bleomycin was more rapid, compared with that in the control mice. The protein levels of Vimentin and phospho-SMAD2 were upregulated, whereas the level of E‑cadherin was downregulated in the MCMV+bleomycin group,. The results suggested that latent MCMV infection aggravated pulmonary fibrosis in the mouse model, possibly through the activation of TGF-β1. PMID:27279470

  11. Anticytomegaloviral activity and safety of cidofovir in patients with human immunodeficiency virus infection and cytomegalovirus viruria.

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    Polis, M A; Spooner, K M; Baird, B F; Manischewitz, J F; Jaffe, H S; Fisher, P E; Falloon, J; Davey, R T; Kovacs, J A; Walker, R E

    1995-01-01

    Cidofovir (HPMPC; (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine) is a nucleotide analog with activity against human cytomegalovirus (CMV). A phase I/II dose escalation trial was conducted with asymptomatic human immunodeficiency virus (HIV)-infected patients with CMV viruria to determine its pharmacokinetics, maximally tolerated dose, and preliminary antiviral activity against CMV. Qualitative CMV blood and urine cultures were monitored weekly to assess anti-CMV activity. Twenty-one HIV-infected persons with CD4 counts from 0 to 389 cells per microliters (median, 39) were enrolled in six dose-ranging groups. The first five groups enrolled four patients each to receive cidofovir infusions either weekly or biweekly for 4 weeks or every 3 weeks for 12 weeks. The sixth group enrolled one patient who received infusions of 5 mg/kg of body weight every other week. Patients receiving 0.5 or 1.5 mg/kg twice weekly experienced no serious toxicity. The first two patients who received 5 mg/kg twice weekly developed glycosuria and 2+ proteinuria. Subsequent patients received concomitant probenecid to attempt to ameliorate renal toxicity. Seventeen patients experienced proteinuria on one or more occasions; 6 of them experienced at least 2+ proteinuria. Four patients did not complete the study as planned because of renal toxicity. Positive CMV urine cultures reverted to negative in 2 of 8 patients receiving doses of < or = 1.5 mg/kg twice weekly and 11 of 13 patients receiving higher doses. Cidofovir has in vivo anti-CMV activity demonstrated by prolonged clearing of CMV viruria, although this observation is tempered by the fact that clearance of viremia could not be demonstrated. The dose-limiting toxicity is renal; however, concurrent administration of probenecid may be protective. The maximally tolerated weekly intravenous dose with probenecid is approximately 5 mg/kg. Efficacy trials with CMV disease will define the therapeutic utility and optimal dosing interval for

  12. Congenital and perinatal cytomegalovirus infection

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    Chun Soo Kim

    2010-01-01

    Full Text Available Cytomegalovirus (CMV is currently the most common agent of congenital infection and the leading infectious cause of brain damage and hearing loss in children. Symptomatic congenital CMV infections usually result from maternal primary infection during early pregnancy. One half of symptomatic infants have cytomegalic inclusion disease (CID, which is characterized by involvement of multiple organs, in particular, the reticuloendothelial and central nervous system (CNS. Moreover, such involvement may or may not include ocular and auditory damage. Approximately 90% of infants with congenital infection are asymptomatic at birth. Preterm infants with perinatal CMV infection can have symptomatic diseases such as pneumonia, hepatitis, and thrombocytopenia. Microcephaly and abnormal neuroradiologic imaging are associated with a poor prognosis. Hearing loss may occur in both symptomatic and asymptomatic infants with congenital infection and may progress through childhood. Congenital infection is defined by the isolation of CMV from infants within the first 3 weeks of life. Ganciclovir therapy can be considered for infants with symptomatic congenital CMV infection involving the CNS. Pregnant women of seronegative state should be counseled on the importance of good hand washing and other control measures to prevent CMV infection. Heat treatment of infected breast milk at 72?#608;for 5 seconds can eliminate CMV completely.

  13. EFFECTS OF IMMUNOSUPPRESSION WITH CYCLOPHOSPHAMIDE ON ACUTE MURINE CYTOMEGALOVIRUS INFECTION AND VIRUS-AUGMENTED NATURAL KILLER CELL ACTIVITY

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    The effects of cyclophosphamide (CY) treatment on acute murine cytomegalovirus (MCMV) infection were studied to explore the potential usefulness of MCMV as a means of detecting immune dysfunction and to identify host defense mechanisms important for protection against MCMV.

  14. Cerebral ultrasound images in prenatal cytomegalovirus infection.

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    Tomà, P; Magnano, G M; Mezzano, P; Lazzini, F; Bonacci, W; Serra, G

    1989-01-01

    A male newborn with prenatal cytomegalovirus infection was referred for cranial ultrasound. The cranial ultrasound demonstrated areas of increased echogenicity in the thalamic and gray nuclei resembling "a branched candlestick". Doppler technique located the "branched candlestick" along the thalamostriate arteries. This image is particularly interesting because to our knowledge it has never before been described in congenital cytomegalovirus infection, but only in congenital rubella. PMID:2550848

  15. Cytomegalovirus Infection and Pre-Eclampsia

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    Rădulescu Carmen; Huţanu Adina; Gabor Rozalia; Şincu Nina

    2016-01-01

    Introduction: Pre-eclampsia is a pregnancy-specific disease characterized by hypertension after 20 weeks of gestation and proteinuria. It is a major cause of maternal and perinatal morbidity and mortality. The pathogenesis of pre-eclampsia is not completely understood. In our study we investigated if there is a potential link between cytomegalovirus infection and pre-eclampsia and if cytomegalovirus infection is the triggering factor of pre-eclampsia.

  16. Cytomegalovirus infection accelerates epigenetic aging.

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    Kananen, Laura; Nevalainen, Tapio; Jylhävä, Juulia; Marttila, Saara; Hervonen, Antti; Jylhä, Marja; Hurme, Mikko

    2015-12-01

    Epigenetic mechanisms such as DNA methylation (DNAm) have a central role in the regulation of gene expression and thereby in cellular differentiation and tissue homeostasis. It has recently been shown that aging is associated with profound changes in DNAm. Several of these methylation changes take place in a clock-like fashion, i.e. correlating with the calendar age of an individual. Thus, the epigenetic clock based on these kind of DNAm changes could provide a new biomarker for human aging process, i.e. being able to separate the calendar and biological age. Information about the correlation of the time indicated by this clock to the various aspects of immunosenescence is still missing. As chronic cytomegalovirus (CMV) infection is probably one of the major driving forces of immunosenescence, we now have analyzed the correlation of CMV seropositivity with the epigenetic age in the Vitality 90+cohort 1920 (122 nonagenarians and 21 young controls, CMV seropositivity rates 95% and 57%, respectively). The data showed that CMV seropositivity was associated with a higher epigenetic age in both of these age groups (median 26.5 vs. 24.0 (p < 0.02,Mann–Whitney U-test) in the young controls and 76.0 vs. 70.0 (p < 0.01) in the nonagenarians). Thus, these data provide a new aspect to the CMV associated pathological processes. PMID:26485162

  17. Rare presentations of cytomegalovirus infection in renal allograft recipients.

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    Ardalan, Mohammadreza

    2012-01-01

    Cytomegalovirus is the most common viral infection after kidney transplantation. Clinical presentations of cytomegalovirus infection range from asymptomatic infection to organ-specific involvement. Most symptomatic infections manifest as fever and cytopenia. The gastrointestinal tract is the most common site of tissue-invasive infection, often presenting as diarrhea or gastrointestinal bleeding. Gastrointestinal obstruction, perforation, thrombosis of large gastrointestinal veins, splenic artery thrombosis, and pancreatitis are rare gastrointestinal presentations of cytomegalovirus infection. Renal-allograft ureteral stricture and skin involvement are other rare presentations of cytomegalovirus infection. hemophagocytic syndrome, thrombotic microangiopathy, adrenal insufficiency, and renal allograft artery stenosis are other rare symptoms of cytomegalovirus infection.

  18. Active human Cytomegalovirus infection and Glycoprotein B genotypes in Brazilian pediatric renal or hematopoietic stem cell transplantation patients

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    Débora de Campos Dieamant

    2010-03-01

    Full Text Available A prospective analysis of active Human Cytomegalovirus infection (HCMV was conducted on 33 pediatric renal or hematopoietic stem cell post-transplant patients. The HCMV-DNA positive samples were evaluated for the prevalence of different gB subtypes and their subsequent correlation with clinical signs. The surveillance of HCMV active infection was based on the monitoring of antigenemia (AGM and on a nested polymerase chain reaction (N-PCR for the detection of HCMV in the patients studied. Using restriction analysis of the gB gene sequence by PCR-RFLP (Restriction Fragment Length Polymorphism, different HCMV strains could be detected and classified in at least four HCMV genotypes. Thirty-three pediatric recipients of renal or bone marrow transplantation were monitored. Twenty out of thirty-three (60.6% patients demonstrated active HCMV infection. gB1 and gB2 genotypes were more frequent in this population. In this study, we observed that gB2 had correlation with reactivation of HCMV infection and that patients with mixture of genotypes did not show any symptoms of HCMV disease. Future studies has been made to confirm this.

  19. Surveillance of active human cytomegalovirus infection in hematopoietic stem cell transplantation (HLA sibling identical donor): search for optimal cutoff value by real-time PCR

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    Aranha Francisco JP; Vigorito Afonso C.; Oliveira Cristiane de; Albuquerque Dulcinéia M; Bonon Sandra HA; Andrade Paula D; Costa Cláudia RC; Peres Renata MB; de Souza Cármino A; Costa Sandra CB

    2010-01-01

    Abstract Background Human cytomegalovirus (CMV) infection still causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, it is extremely important to diagnosis and monitor active CMV infection in HSCT patients, defining the CMV DNA levels of virus replication that warrant intervention with antiviral agents in order to accurately prevent CMV disease and further related complications. Methods During the first 150 days after allogenei...

  20. Human Cytomegalovirus Manipulation of Latently Infected Cells

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    John H. Sinclair

    2013-11-01

    Full Text Available Primary infection with human cytomegalovirus (HCMV results in the establishment of a lifelong infection of the host which is aided by the ability of HCMV to undergo a latent infection. One site of HCMV latency in vivo is in haematopoietic progenitor cells, resident in the bone marrow, with genome carriage and reactivation being restricted to the cells of the myeloid lineage. Until recently, HCMV latency has been considered to be relatively quiescent with the virus being maintained essentially as a “silent partner” until conditions are met that trigger reactivation. However, advances in techniques to study global changes in gene expression have begun to show that HCMV latency is a highly active process which involves expression of specific latency-associated viral gene products which orchestrate major changes in the latently infected cell. These changes are argued to help maintain latent infection and to modulate the cellular environment to the benefit of latent virus. In this review, we will discuss these new findings and how they impact not only on our understanding of the biology of HCMV latency but also how they could provide tantalising glimpses into mechanisms that could become targets for the clearance of latent HCMV.

  1. Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model.

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    Slavuljica, Irena; Kveštak, Daria; Huszthy, Peter Csaba; Kosmac, Kate; Britt, William J; Jonjić, Stipan

    2015-03-01

    Congenital human cytomegalovirus infection is a leading infectious cause of long-term neurodevelopmental sequelae, including mental retardation and hearing defects. Strict species specificity of cytomegaloviruses has restricted the scope of studies of cytomegalovirus infection in animal models. To investigate the pathogenesis of congenital human cytomegalovirus infection, we developed a mouse cytomegalovirus model that recapitulates the major characteristics of central nervous system infection in human infants, including the route of neuroinvasion and neuropathological findings. Following intraperitoneal inoculation of newborn animals with mouse cytomegalovirus, the virus disseminates to the central nervous system during high-level viremia and replicates in the brain parenchyma, resulting in a focal but widespread, non-necrotizing encephalitis. Central nervous system infection is coupled with the recruitment of resident and peripheral immune cells as well as the expression of a large number of pro-inflammatory cytokines. Although infiltration of cellular constituents of the innate immune response characterizes the early immune response in the central nervous system, resolution of productive infection requires virus-specific CD8(+) T cells. Perinatal mouse cytomegalovirus infection results in profoundly altered postnatal development of the mouse central nervous system and long-term motor and sensory disabilities. Based on an enhanced understanding of the pathogenesis of this infection, prospects for novel intervention strategies aimed to improve the outcome of congenital human cytomegalovirus infection are proposed.

  2. Acute cytomegalovirus infections in leukemic mice.

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    Mayo, D. R.; Rapp, F

    1980-01-01

    Mice infected with 2 x 10(3) plaque-forming units of mouse cytomegalovirus (MCMV) 3 days after receiving 300 to 400 spleen focus-forming units of Friend leukemia virus developed a more severe MCMV infection than did normal animals. Increased severity was demonstrated by the increased amounts of MCMV recoverable from the salivary glands of leukemic mice 1 to 5 weeks postinfection. In addition, the difference in the number of virus isolations from the kidneys, spleens, livers, and lungs of anim...

  3. Experimental Study of Mouse Cytomegalovirus Infected Mice

    Institute of Scientific and Technical Information of China (English)

    崔雯; 董永绥; 方峰

    2002-01-01

    Summary: In order to investigate the human cytomegalovirus (HCMV) infection, the mouse cytomegalovirus (MCMV) infected mice were experimentally studied. 6 to 8 week old female BALB/C mice with immunosuppression were selected to undergo the MCMV inoculations: intracranial inoculation and peritoneal inoculation. MCMV of the infected mice in various organs and tissues were detected by using β-gal staining and in situ nucleic acid hybridization assay. The pathological changes were observed in HE staining paraffin-embedded sections. It was found that all the MCMV infected mice showed the retardation of growth and development, and feather looseness. Both intracranial inoculation of 104 PFU viruses or peritoneal inoculation of 106 PFU viruses resulted in the pathological changes, to some extent, of various organs and tissues in the mice. The pathological changes in liver were consistent with the amount of β-gal staining positive cells, indicating the liver lesions were mainly caused by viral proliferation. It was also found that the viruses in the immunosuppressed mice subjected to intracranial inoculation could spread to whole body organs, while the viruses in the immunosuppressed mice subjected to intrapeitoneal inoculation couldn't spread to the brain, suggesting blood-brain barrier could prevent the virus from spreading to the brain.

  4. Optimum treatment of congenital cytomegalovirus infection.

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    Leruez-Ville, Marianne; Ville, Yves

    2016-01-01

    Congenital cytomegalovirus infection affects 0.7% of live births and is the leading cause of congenital neurological handicaps of infectious origin. However, systematic screening of this infection has not been implemented in pregnancy or at birth in any country. This apparent paradox has been justified by the unavailability of an efficient vaccine and by the scarcity of data available on the treatment of congenital CMV. However, in the last decade interesting new data on the management of this congenital infection has emerged including new results on both neonatal and postnatal treatments. This review provides an update on the potential benefits of antiviral treatment and on passive immunisation both in the neonatal and the antenatal periods. These suggest a benefit to a proactive approach for neonatal and prenatal congenital infections. PMID:27043943

  5. Activation of Langerhans-Type Dendritic Cells Alters Human Cytomegalovirus Infection and Reactivation in a Stimulus-Dependent Manner

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    Coronel, Roxanne; Jesus, Desyree M.; Dalle Ore, Lucia; Mymryk, Joe S.; Hertel, Laura

    2016-01-01

    Oral mucosal Langerhans cells (LC) are likely to play important roles in host defense against infection by human cytomegalovirus (CMV). We previously showed that in vitro-differentiated immature LC (iLC) populations contain smaller amounts of infected cells but produce higher yields than mature LC (mLC) cultures, obtained by iLC stimulation with fetal bovine serum (FBS), CD40 ligand (CD40L) and lipopolysaccharide (LPS). Here, we sought to determine if exposure to select stimuli can improve LC permissiveness to infection, if specific components of the mLC cocktail are responsible for lowering viral yields, if this is due to defects in progeny production or release, and if these restrictions are also effective against reactivated virus. None of the stimuli tested extended the proportion of infected cells to 100%, suggesting that the block to infection onset cannot be fully removed. While CD40L and FBS exerted positive effects on viral progeny production per cell, stimulation with LPS alone or in combination with CD40L was detrimental. Reductions in viral titers were not due to defects in progeny release, and the permissive or restrictive intracellular environment established upon exposure to each stimulus appeared to act in a somewhat similar way toward lytic and latent infections.

  6. Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection

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    Fatehi Elnour Elzein

    2016-01-01

    Full Text Available The mortality in Strongyloides hyperinfection syndrome (SHS is alarmingly high. This is particularly common in bone marrow, renal, and other solid organ transplant (SOT patients, where figures may reach up to 50–85%. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy. Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus (CMV and strongyloidiasis had rarely been associated. We here describe a patient who survived SHS with recurrent Escherichia coli (E. coli urosepsis and CMV infection.

  7. GWAS, Cytomegalovirus Infection, and Schizophrenia

    DEFF Research Database (Denmark)

    Grove, Jakob; Børglum, Anders; Pearce, Brad D

    2014-01-01

    In recent years, good progress has been made in uncovering the genetic underpinnings of schizophrenia. Even so, as a polygenic disorder, schizophrenia has a complex etiology that is far from understood. Meanwhile, data are being collected enabling the study of interactions between genes...... and the environment. A confluence of data from genetic and environmental exposure studies point to the role of infections and immunity in the pathophysiology of schizophrenia. In a recent study by Børglum et al., a single nucleotide polymorphism (SNP) in the gene CTNNA3 was identified that may provide clues to gene......-environment interactions. The carriers of the minor allele for the SNP had a fivefold risk of later developing schizophrenia if their mothers were CMV positive, while the children not carrying the allele had no excess risk from maternal CMV. In the current paper, we summarize recent advances to clarify a possible...

  8. [Complications of systemic cytomegalovirus infection in therapy-resistant Hodgkin's lymphoma].

    Science.gov (United States)

    Irsai, Gábor; Tampu-Kiss, Tatjana; Dezső, Balázs; Miltényi, Zsófia; Illés, Arpád; Méhes, Gábor

    2012-05-13

    Cytomegalovirus infection related changes frequently remain masked by local symptoms of tumor invasion or therapeutic side effects in cancer patients. The spectrum of cytomegalovirus manifestations, however, can be highly varied and may contribute to the failure of different organs with fatal outcome. The case of a 29-year-old female patient is presented who obtained polychemotherapy and allogenic stem cell transplantation following the diagnosis of classical Hodgkin's disease. Despite intensified treatment, only partial response could be achieved and the outcome of the disease was death. Postmortem examination revealed regressive lymph node infiltration as well as nodular liver and spleen manifestations of classical Hodgkin's disease. In addition, parenchymal tissues (lung, kidneys, small intestine, liver, pancreas and ovaries) showed the classical morphology of widespread cytomegalovirus infection. Bilateral enlargement of the ovaries was caused by a partially necrotic giant cell proliferation in the subepithelial cortex. CD30-negativity and cytomegalovirus antigen positivity of the large atypical cell infiltrate supported the diagnosis of cytomegalia oophoritis with morphological overlap between cytomegalovirus-infected giant cells and residual Hodgkin-Reed-Sternberg cells. Further to the cytopathic effect in multiple organs, significant hemophagocytosis was also observed in the spleen, liver and bone marrow. In summary, active cytomegalovirus infection may be a major cause of multi-organ failure in the immunosuppressed oncohematological patient. Careful postmortem analysis demonstrated both the activity of the viral infection and the efficacy of the anti-viral treatment, when applied.

  9. Peptide inhibition of human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2011-02-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100

  10. [{sup 11}C]FMAU and [{sup 18}F]FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Erik F.J. de E-mail: e.f.j.de.vries@pet.azg.nl; Waarde, Aren van; Harmsen, Marco C.; Mulder, Nanno H.; Vaalburg, Willem; Hospers, Geke A.P

    2000-02-01

    [{sup 11}C]-2'-Fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 11}C]FMAU) and [{sup 18}F]-9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([{sup 18}F]FHPG), radiolabeled representatives of two classes of antiviral agents, were evaluated as tracers for measuring herpes simplex virus thymidine kinase (HSV-tk) enzyme activity after gene transfer and as tracers for localization of active human cytomegalovirus (HCMV) infections. In vitro accumulation experiments revealed that both [{sup 11}C]FMAU and [{sup 18}F]FHPG accumulated significantly more in HSV-tk expressing cells than they did in control cells. [{sup 18}F]FHPG uptake in HSV-tk expressing cells, however, was found to depend strongly on the cell line used, which might be due to cell type dependent membrane transport or cell type dependent substrate specific susceptibility of the enzyme. In vitro, both tracers exhibited a good selectivity for accumulation in HCMV-infected human umbilical vein endothelial cells over uninfected cells. In contrast to [{sup 18}F]FHPG, [{sup 11}C]FMAU uptake in control cells was relatively high due to phosphorylation of the tracer by host kinases. Therefore, [{sup 18}F]FHPG appears to be the more selective tracer not only to predict HSV-tk gene therapy outcome, but also to localize active HCMV infections with PET.

  11. Prognostic markers of symptomatic congenital cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Roberta Maia de Castro Romanelli

    2008-02-01

    Full Text Available The objective of this research was to identify maternal and fetal characteristics as prognostic markers of congenital cytomegalovirus (CMV infection. This is a descriptive study of 13 cases of congenital CMV infection referred to Institute de Puericulture et Perinatologie de Paris (IPP from January 2005 to October 2006. Amniotic fluid puncture was performed to research CMV polimerase chain reaction (PCR. Cordocentesis and cord blood samples at delivery were also analyzed to determinate fetal platelets count, GGT, ASAT, ALAT, CMV-DNA and IgM antibody. Variables of symptomatic and asymptomatic infants were then compared. Data were analyzed by SPSS - 15.0. Mean gestational age of amniocentesis was 24.6 weeks and there was no difference of mean viral load in amniotic fluid considering infant features. Mean gestational age of cordocentesis was 26.1 weeks. There were no statistical differences of fetal viral load, IgM, platelets, GGT, ASAT and ALAT analyzed at cordocentesis samples, but at delivery, mean values of IgM and ASAT of fetal blood were increased in symptomatic ones (p= 0.03 for both parameters. When considering groups with normal and abnormal parameters, ASAT of cordon samples was also increased in symptomatic infants (p= 0.02. Sensibility, specificity, positive and negative predictive value of fetal ultrasound anomalies to detect symptomatic infants were, respectively, 80%, 62.5%, 57.1% and 83.3%. Thus, identification of markers of CMV symptomatic infants should be aimed. Prenatal diagnosis, identification and follow up of congenital CMV infected infants are important to consider treatment for symptomatic infants, trying to avoid or reducing some possible sequels.

  12. Surveillance of active human cytomegalovirus infection in hematopoietic stem cell transplantation (HLA sibling identical donor: search for optimal cutoff value by real-time PCR

    Directory of Open Access Journals (Sweden)

    Aranha Francisco JP

    2010-06-01

    Full Text Available Abstract Background Human cytomegalovirus (CMV infection still causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT. Therefore, it is extremely important to diagnosis and monitor active CMV infection in HSCT patients, defining the CMV DNA levels of virus replication that warrant intervention with antiviral agents in order to accurately prevent CMV disease and further related complications. Methods During the first 150 days after allogeneic HSTC, thirty patients were monitored weekly for active CMV infection by pp65 antigenemia, nested-PCR and real-time PCR assays. Receiver operating characteristic (ROC plot analysis was performed to determine a threshold value of the CMV DNA load by real-time PCR. Results Using ROC curves, the optimal cutoff value by real-time PCR was 418.4 copies/104 PBL (sensitivity, 71.4%; specificity, 89.7%. Twenty seven (90% of the 30 analyzed patients had active CMV infection and two (6.7% developed CMV disease. Eleven (40.7% of these 27 patients had acute GVHD, 18 (66.7% had opportunistic infection, 5 (18.5% had chronic rejection and 11 (40.7% died - one died of CMV disease associated with GVHD and bacterial infection. Conclusions The low incidence of CMV disease in HSCT recipients in our study attests to the efficacy of CMV surveillance based on clinical routine assay. The quantification of CMV DNA load using real-time PCR appears to be applicable to the clinical practice and an optimal cutoff value for guiding timely preemptive therapy should be clinically validated in future studies.

  13. Prevention of Primary Cytomegalovirus Infection in Pregnancy☆

    Science.gov (United States)

    Revello, Maria Grazia; Tibaldi, Cecilia; Masuelli, Giulia; Frisina, Valentina; Sacchi, Alessandra; Furione, Milena; Arossa, Alessia; Spinillo, Arsenio; Klersy, Catherine; Ceccarelli, Manuela; Gerna, Giuseppe; Todros, Tullia

    2015-01-01

    Background Cytomegalovirus (CMV) is the leading infectious agent causing congenital sensorineural hearing loss and psychomotor retardation. CMV vaccine is currently unavailable and treatment options in pregnancy are limited. Susceptible pregnant women caring for children are at high risk for primary infection. CMV educational and hygienic measures have the potential to prevent primary maternal infection. Methods A mixed interventional and observational controlled study was conducted to investigate the effectiveness of hygiene information among pregnant women at risk for primary CMV infection for personal/occupational reasons. In the intervention arm, CMV-seronegative women, identified at the time of maternal serum screening for fetal aneuploidy at 11–12 weeks of gestation, were given hygiene information and prospectively tested for CMV until delivery. The comparison arm consisted of women enrolled at delivery who were neither tested for nor informed about CMV during pregnancy, and who had a serum sample stored at the screening for fetal aneuploidy. By design, groups were homogeneous for age, parity, education, and exposure to at least one risk factor. The primary outcome was CMV seroconversion. Acceptance of hygiene recommendations was a secondary objective and was measured by a self-report. Findings Four out of 331 (1.2%) women seroconverted in the intervention group compared to 24/315 (7.6%) in the comparison group (delta = 6.4%; 95% CI 3.2–9.6; P < 0.001). There were 3 newborns with congenital infection in the intervention group and 8 in the comparison group (1 with cerebral ultrasound abnormalities at birth). Ninety-three percent of women felt hygiene recommendations were worth suggesting to all pregnant women at risk for infection. Interpretation This controlled study provides evidence that an intervention based on the identification and hygiene counseling of CMV-seronegative pregnant women significantly prevents maternal infection. While waiting for

  14. Animal cytomegaloviruses.

    OpenAIRE

    Staczek, J.

    1990-01-01

    Cytomegaloviruses are agents that infect a variety of animals. Human cytomegalovirus is associated with infections that may be inapparent or may result in severe body malformation. More recently, human cytomegalovirus infections have been recognized as causing severe complications in immunosuppressed individuals. In other animals, cytomegaloviruses are often associated with infections having relatively mild sequelae. Many of these sequelae parallel symptoms associated with human cytomegalovir...

  15. Acute cytomegalovirus infection complicated by venous thrombosis: a case report

    Directory of Open Access Journals (Sweden)

    Parola Philippe

    2005-08-01

    Full Text Available Abstract Background CMV-induced vasculopathy and thrombosis have been reported, but they are rare conditions usually encountered in immunocompromised patients. However more and more complications of CMV infections are recognized in immunocompetent patients. Case presentation We present a case report of a previously healthy adult with cytomegalovirus infection that was complicated by tibiopopliteal deep venous thrombosis and in whom Factor V Leiden heterozygous mutation was found. Conclusion This new case report emphasizes the involvement of cytomegalovirus in induction of vascular thrombosis in patients with predisposing risk factors for thrombosis. It is necessary to screen for CMV infection in patients with spontaneous thrombosis and an history of fever.

  16. Congenital cytomegalovirus infection: new prospects for prevention and therapy.

    Science.gov (United States)

    Swanson, Elizabeth C; Schleiss, Mark R

    2013-04-01

    Cytomegalovirus is the commonest congenital viral infection in the developed world, with an overall prevalence of approximately 0.6%. Approximately 10% of congenitally infected infants have signs and symptoms of disease at birth, and these symptomatic infants have a substantial risk of subsequent neurologic sequelae. These include sensorineural hearing loss, mental retardation, microcephaly, development delay, seizure disorders, and cerebral palsy. Antiviral therapy for children with symptomatic congenital cytomegalovirus infection is effective at reducing the risk of long-term disabilities and should be offered to families with affected newborns. An effective preconceptual vaccine against CMV could protect against long-term neurologic sequelae and other disabilities.

  17. Infection of human endothelium in vitro by cytomegalovirus causes enhanced expression of purinergic receptors : A potential virus escape mechanism?

    NARCIS (Netherlands)

    Zandberg, Mariet; van Son, Willem J.; Harmsen, Martin C.; Bakker, Winston W.

    2007-01-01

    Background. Human cytomegalovirus (CMV) uses different strategies to escape from human host defense reactions. Previously we have observed that infection of endothelial cells with CMV in vitro leads to enhanced activity of endothelial ectonucleotidases. These ectoenzymes are responsible for hydrolys

  18. Autism in a Child with Congenital Cytomegalovirus Infection.

    Science.gov (United States)

    Markowitz, Phillip I.

    1983-01-01

    A case study is described in which early infantile autism was diagnosed in a child with congenital cytomegalovirus (CMU) infection. It is suggested that congenital infection should be considered as an etiological agent in autism. The case's synergistic effect of CMU-induced brain damage, deafness, and maternal deprivation in noted. (CL)

  19. PP65 antigenemia in the diagnosis of cytomegalovirus infection in AIDS patients

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    RC Capela

    2012-01-01

    Full Text Available Cytomegalovirus causes significant morbidity and mortality in AIDS patients and those having undergone bone marrow or another transplant. PP65 antigenemia is based on detecting viral antigen in peripheral blood leukocytes through immunochemistry and by monitoring the infection in immunocompromised individuals. The present study aimed to set up this diagnostic technique in AIDS patients with active cytomegalovirus infection and verify its occurrence in the Botucatu region of São Paulo state, Brazil. Fifty patients, 35 men and 15 women aged from 24 to 69 years, were recruited from those attended at the Department of Tropical Diseases of Botucatu Medical School, UNESP, and divided into three groups according to CD4+ T lymphocyte counts and antiretroviral treatment. The control group comprised bone marrow transplant patients. Fourteen AIDS patients with low CD4+ cell counts tested positive for PP65 antigenemia, which could predict cytomegalovirus infection and indicate prophylactic treatment.

  20. Effects of Jinye Baidu Granule(金叶败毒颗粒) on Fetal Growth and Development with Maternal Active Human Cytomegalovirus Infection

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To evaluate the effects of Jinye Baidu Granule (金叶败毒颗粒, JYBDG), a traditional Chinese medicine compound prescription, on fetal growth and development with maternal active human cytomegalovirus infection. Methods: A prospective, randomized and controlled trial was adopted during January 1996 to June 2002. From the pregnant women with an abnormal pregnant history, 240 cases were screened to be infected by human cytomegalovirus (HCMV) by enzyme-linked immunoabsorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). They were assigned according to the random number table to two groups. The 122 cases in the treatment group were administrated with JYBDG, one package each time, three times a day for two continuous weeks, while the other 118 in the control group did not receive any treatment. The negative conversion rate of both HCMV-IgM and HCMV late mRNA,the positive rate of HCMV-DNA in placenta and the intrauterine transmission rate between the two groups were compared, and fetal growth and development in partial fetuses were also observed. Results: The negative conversion rate of both HCMV-IgM and HCMV late mRNA, the positive rate of HCMV-DNA in placenta and the intrauterine transmission rate in the treatment group were 77. 05% (94/122), 48. 98% (48/98) and 21.74% (10/46) respectively, while those in the control group were 38. 14% (45/118), 67.50% (54/80)and 52.63% (20/38) respectively, all showing significant difference between the two groups (P<0.01).Totally 35 normal infants and 11 abnormal infants were born in the treatment group, and the number in the control group was 20 and 18 respectively, and comparison between the two groups showed significant difference (P<0.01). Six months of child birth, the scores of both mental development index (MDI) and psychomotor development index (PDI) of infants were higher in the treatment group (20 cases) than those in the control group (20 cases), but there was no significant

  1. Cytomegalovirus (CMV) Infection: A Guide for Patients and Families After Stem Cell Transplant

    Science.gov (United States)

    ... Infection: A Guide for Patients and Families after Stem Cell Transplant What is cytomegalovirus (CMV)? Cytomegalovirus (CMV), a ... weakened by medicines that you must take after stem cell transplant and by the transplant itself. Your body ...

  2. Impaired arterial reactivity following cytomegalovirus infection in the immunosuppressed rat.

    OpenAIRE

    Eerdmans, P. H.; Persoons, M. C.; Debets, S. J.; Struijker Boudier, H. A.; Smits, J. F.; Bruggeman, C. A.; De Mey, J. G.

    1996-01-01

    1. Cytomegalovirus (CMV) is a major pathogen in immunocompromised individuals and may participate in the pathogenesis of atherosclerosis in the general population. We evaluated whether CMV-infection alters the function of arterial smooth muscle. 2. Blood pressure (BP) and arterial reactivity were recorded in immunosuppressed rats that had been infected with CMV (10(5) plaque forming units i.p.). Furthermore, the reactivity of isolated arteries was compared between CMV-infected rats and rats i...

  3. Possible contribution of cytomegalovirus infection to the high risk of (recurrent) venous thrombosis after renal transplantation

    NARCIS (Netherlands)

    Lijfering, Willem M.; de Vries, Aiko R. J.; Veeger, Nic J. G. M.; van Son, Willem J.; Bakker, Stephan J. L.; van der Meer, Jan

    2008-01-01

    Renal transplant recipients are at an increased risk of venous thrombosis, which has been regarded as a postoperative complication, although it may persist afterwards. As numerous case reports have shown that active cytomegalovirus (CMV) infection can be found at time of onset of venous thrombosis,

  4. Infantile Spasms and Cytomegalovirus Infection: Antiviral and Antiepileptic Treatment

    Science.gov (United States)

    Dunin-Wasowicz, Dorota; Kasprzyk-Obara, Jolanta; Jurkiewicz, Elzbieta; Kapusta, Monika; Milewska-Bobula, Bogumila

    2007-01-01

    From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before…

  5. Cytomegalovirus infection in a pig in South Africa

    Directory of Open Access Journals (Sweden)

    M.G. Collett

    2002-07-01

    Full Text Available An 8-week-old piglet with dyspnoea, bilateral mucopurulent nasal discharge and mouth breathing was euthanased and a necropsy was performed. Apart from histological evidence of diffuse rhinitis, large intranuclear inclusion bodies, pathognomonic for porcine cytomegalovirus infection, were detected within mucous glands on the nasal turbinates. This is the first such case to be diagnosed in South Africa.

  6. Specific endoscopic features of ulcerative colitis complicated by cytomegalovirus infection

    Institute of Scientific and Technical Information of China (English)

    Hideyuki; Suzuki; Jun; Kato; Motoaki; Kuriyama; Sakiko; Hiraoka; Kenji; Kuwaki; Kazuhide; Yamamoto

    2010-01-01

    AIM:To identify specific colonoscopic findings in patients with ulcerative colitis (UC) complicated by cyto-megalovirus (CMV) infection.METHODS: Among UC patients who were hospitalized due to exacerbation of symptoms, colonoscopic findings were compared between 15 CMV-positive patients and 58 CMV-negative patients. CMV infection was determined by blood test for CMV antigenemia. Five aspects of mucosal changes were analyzed (loss of vascular pattern, erythema, mucosal edema, easy bleeding, and mucinous exuda...

  7. EFFECT OF CYTOMEGALOVIRUS INFECTION ON THE PREDICTIVE VALUE OF CD-40 LIGAND IN HEART TRANSPLANT RECIPIENTS

    Directory of Open Access Journals (Sweden)

    O. P. Shevchenko

    2012-01-01

    Full Text Available Cytomegalovirus infection may be associated with the development of acute cellular rejection – the most fre- quent and serious complication after heart transplantation, limiting long-term survival of recipients. Biomarkers of inflammation and thrombosis, one of which is the product of platelet activation – a soluble CD40 ligand (sCD40L, also play an important role in the immunopathology of acute rejection. The aim of the study was to assess the risk of cardiovascular complications after heart transplantation under the combined effect of two factors – sCD40L and cytomegalovirus infection. We examined 64 heart recipients in the period of 12 years after heart transplantation. It was revealed that with the presence of elevated levels of sCD40L in combination with cytomegalovirus infection, risk of acute cellular rejection is higher. In recipients with low levels of sCD40L and without cytomegalovirus infection survival rate is significantly higher than in recipients with the presence of one or both of the studied risk factors. 

  8. Bioactive molecules released from cells infected with the Human Cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Anna eLuganini

    2016-05-01

    Full Text Available Following primary infection in humans, the Human Cytomegalovirus (HCMV persists in a latent state throughout the host’s lifetime despite a strong and efficient immune response. If the host experiences some form of immune dysregulation, such as immunosuppression or immunodeficiency, HCMV reactivates, thereby emerging from latency. Thus, in the absence of effective functional immune responses, as occurs in immunocompromised or immunoimmature individuals, both HCMV primary infections and reactivations from latency can cause significant morbidity and mortality. However, even in immunocompetent hosts, HCMV represents a relevant risk factor for the development of several chronic inflammatory diseases and certain forms of neoplasia. HCMV infection may shift between the lytic and latent state, regulated by a delicate and intricate balance between virus-mediated immunomodulation and host immune defenses. Indeed, HCMV is a master in manipulating innate and adaptive host defense pathways, and a large portion of its genome is devoted to encoding immunomodulatory proteins; such proteins may thus represent important virulence determinants. However, the pathogenesis of HCMV-related diseases is strengthened by the activities of bioactive molecules, of both viral and cellular origin, that are secreted from infected cells and collectively named as the secretome. Here, we review the state of knowledge on the composition and functions of HCMV-derived secretomes. In lytic infections of fibroblasts and different types of endothelial cells, the majority of HCMV-induced secreted proteins act in a paracrine fashion to stimulate the generation of an inflammatory microenvironment around infected cells; this may lead to vascular inflammation and angiogenesis that, in turn, foster HCMV replication and its dissemination through host tissues. Conversely, the HCMV secretome derived from latently infected hematopoietic progenitor cells induces an immunosuppressive

  9. Eosinophilic gastroenteritis with cytomegalovirus infection in an immunocompetent child

    Institute of Scientific and Technical Information of China (English)

    Junji Takeyama; Daiki Abukawa; Katsushi Miura

    2007-01-01

    A 3-year-old boy developed transient protein-losing gastroenteropathy associated with cytomegalovirus (CMV) infection. Both IgG and IgM antibodies to CMV were positive in a serologic blood test. Upper gastrointestinal endoscopy showed multiple erosions throughout the body of the stomach, without enlarged gastric folds. Histological examination of the biopsy specimens indicated eosinophilic gastroenteritis and CMV infection. The patient had complete resolution without specific therapy for CMV in four weeks. An allergic reaction as well as CMV infection played important roles in the pathogenesis of this case.

  10. Prevention of maternal cytomegalovirus infection: current status and future prospects

    Directory of Open Access Journals (Sweden)

    Jessica L Nyholm

    2010-02-01

    Full Text Available Jessica L Nyholm1, Mark R Schleiss21Department of Obstetrics, Gynecology, and Women’s Health, and 2Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN, USAAbstract: Human cytomegalovirus (CMV infection is the most common cause of perinatal viral infection in the developed world, resulting in approximately 40,000 congenitally infected infants in the United States each year. Congenital CMV infection can produce varying degrees of neurodevelopmental disabilities. The significant impact of congenital CMV has led the Institute of Medicine to rank development of a CMV vaccine as a top priority. Vaccine development has been ongoing; however no licensed CMV vaccine is currently available. Treatment of pregnant women with CMV hyperimmune globulin has shown promising results, but has not been studied in randomized controlled trials. Education on methods to prevent CMV transmission, particularly among young women of child-bearing age, should continue until a CMV vaccine becomes available. The epidemiology, clinical manifestations, prevention strategies, and treatment of CMV infections are reviewed.Keywords: cytomegalovirus, CMV vaccines, congenital CMV, CMV infection, immunoglobulin

  11. Probable neuroimmunological link between Toxoplasma and cytomegalovirus infections and personality changes in the human host

    Directory of Open Access Journals (Sweden)

    Roubalová Kateřina

    2005-07-01

    Full Text Available Abstract Background Recently, a negative association between Toxoplasma-infection and novelty seeking was reported. The authors suggested that changes of personality trait were caused by manipulation activity of the parasite, aimed at increasing the probability of transmission of the parasite from an intermediate to a definitive host. They also suggested that low novelty seeking indicated an increased level of the neurotransmitter dopamine in the brain of infected subjects, a phenomenon already observed in experimentally infected rodents. However, the changes in personality can also be just a byproduct of any neurotropic infection. Moreover, the association between a personality trait and the toxoplasmosis can even be caused by an independent correlation of both the probability of Toxoplasma-infection and the personality trait with the third factor, namely with the size of living place of a subject. To test these two alternative hypotheses, we studied the influence of another neurotropic pathogen, the cytomegalovirus, on the personality of infected subjects, and reanalyzed the original data after the effect of the potential confounder, the size of living place, was controlled. Methods In the case-control study, 533 conscripts were tested for toxoplasmosis and presence of anti-cytomegalovirus antibodies and their novelty seeking was examined with Cloninger's TCI questionnaire. Possible association between the two infections and TCI dimensions was analyzed. Results The decrease of novelty seeking is associated also with cytomegalovirus infection. After the size of living place was controlled, the effect of toxoplasmosis on novelty seeking increased. Significant difference in novelty seeking was observed only in the largest city, Prague. Conclusion Toxoplasma and cytomegalovirus probably induce a decrease of novelty seeking. As the cytomegalovirus spreads in population by direct contact (not by predation as with Toxoplasma, the observed changes are

  12. Cytomegalovirus

    Science.gov (United States)

    ... who survive are at an increased risk for hearing loss and mental disability. However, only 1% of newborns who are infected ... treatment is best for me? Are there any activities I should restrict while ... stop breastfeeding my baby? I work at a daycare center. How long should I ...

  13. Symptomatic primary cytomegalovirus infection in a HIV-positive pregnant woman.

    LENUS (Irish Health Repository)

    Bergin, Sarah

    2014-12-01

    We describe a case of symptomatic primary Cytomegalovirus infection in a HIV-positive pregnant woman on antiretroviral treatment with a CD4 count >200 × 10(6)\\/l requiring intravenous ganciclovir. No adverse consequences from ganciclovir or evidence of congenital Cytomegalovirus infection were found.

  14. Dynamics of the cellular metabolome during human cytomegalovirus infection.

    Directory of Open Access Journals (Sweden)

    Joshua Munger

    2006-12-01

    Full Text Available Viral replication requires energy and macromolecular precursors derived from the metabolic network of the host cell. Despite this reliance, the effect of viral infection on host cell metabolic composition remains poorly understood. Here we applied liquid chromatography-tandem mass spectrometry to measure the levels of 63 different intracellular metabolites at multiple times after human cytomegalovirus (HCMV infection of human fibroblasts. Parallel microarray analysis provided complementary data on transcriptional regulation of metabolic pathways. As the infection progressed, the levels of metabolites involved in glycolysis, the citric acid cycle, and pyrimidine nucleotide biosynthesis markedly increased. HCMV-induced transcriptional upregulation of specific glycolytic and citric acid cycle enzymes mirrored the increases in metabolite levels. The peak levels of numerous metabolites during infection far exceeded those observed during normal fibroblast growth or quiescence, demonstrating that HCMV markedly disrupts cellular metabolic homeostasis and institutes its own specific metabolic program.

  15. Growth in Agarose of Human Cells Infected with Cytomegalovirus

    Science.gov (United States)

    Lang, David J.; Montagnier, Luc; Latarjet, Raymond

    1974-01-01

    After infection by human cytomegalovirus (CMV), human diploid fibroblasts could grow in agarose medium for several generations. Clones of infected cells grew for weeks, although in every case they ultimately underwent lysis owing to the cytopathic effect of the virus. Virus was inoculated at high dilution and after UV irradiation in an effort to derive cells infected with noninfectious defective particles still capable of inducing cell stimulation. Dilute or irradiated virus occasionally yielded large colonies of replicating cells, although permanent transformation was not observed. One clone derived from UV-CMV-infected cells was passaged four times before undergoing lysis. During these passages the cells exhibited alterations in morphology and orientation. Images PMID:4367907

  16. Intraperitoneal administration of cytomegalovirus hyperimmunoglobulin to the cytomegalovirus-infected fetus.

    Science.gov (United States)

    Negishi, H; Yamada, H; Hirayama, E; Okuyama, K; Sagawa, T; Matsumoto, Y; Fujimoto, S

    1998-01-01

    Twenty-five percent of cytomegalovirus (CMV)-infected fetuses had sequelae and 8% of those in the recurrent-infected group had sequelae. There is no report yet on the fetal therapy for CMV infections. A Japanese pregnant woman with intrauterine fetal CMV infection diagnosed at 26 weeks of pregnancy is presented. CMV culture of amniotic fluid was positive. A CMV DNA assay using the polymerase chain reaction method of the cord blood and the amniotic fluid was positive during the pregnancy; however, testing for fetal serum CMV-specific IgM was negative. The CMV IgG titer of fetal serum at 27 weeks of pregnancy was a third of that of the maternal serum. CMV hyperimmunoglobulin was injected into the fetal abdominal cavity at 28 and 29 weeks of pregnancy. A second administration of CMV hyperimmunoglobulin increased the titer of CMV IgG in the fetal circulation. At birth, the urine culture was positive for CMV. However, CMV DNA of the ascites became negative. A brain CT scan performed 2 weeks after birth revealed some small calcifications beside the right ventricle. CMV hyperimmunoglobulin injection to the fetal abdominal cavity has been shown to increase the IgG in the fetal serum. This is the first report of fetal therapy of congenital CMV infection. PMID:9848763

  17. Congenital cytomegalovirus infection after recurrent infection: case reports and review of the literature.

    NARCIS (Netherlands)

    Gaytant, M.A.; Rours, G.I.J.G.; Steegers, E.A.P.; Galama, J.M.D.; Semmekrot, B.A.

    2003-01-01

    Cytomegalovirus (CMV) is one of the most common causes of congenital infections in developed countries with reported incidences varying between 0.15% and 2.0%. The effects of congenital CMV infection may vary from a congenital syndrome to an asymptomatic course. Infants that are asymptomatic at birt

  18. Prevention of Primary Cytomegalovirus Infection in Pregnancy

    Directory of Open Access Journals (Sweden)

    Maria Grazia Revello

    2015-09-01

    Interpretation: This controlled study provides evidence that an intervention based on the identification and hygiene counseling of CMV-seronegative pregnant women significantly prevents maternal infection. While waiting for CMV vaccine to become available, the intervention described may represent a responsible and acceptable primary prevention strategy to reduce congenital CMV.

  19. Magnetic resonance imaging of the brain in congenital cytomegalovirus infection

    International Nuclear Information System (INIS)

    The children (age 2 months to 8 years) with a congenital cytomegalovirus (CMV) infection were studied by magnetic resonance imaging (MRI) using a 2.35 Tesla magnet. CMV infection was confirmed by serological investigations and virus culture in the neonatal period. Nine children had severe mental retardation and cerebral palsy, 1 patient suffered from microcephaly, ataxia and deafness. The cranial MRI examination showed the following abnormalities (N): Dilated lateral ventricles (10) and subarachnoid space (8), oligo/pacgyria (8), delayed/pathological myelination (7), paraventricular cysts (6), intra-cerebral calcification (1). This lack of sensitivity for calcification is explainable by the basic principles of MRI. The paraventricular cystic lesions were adjacent ot the occipital horns of the lateral ventricles and separated only by a thin membrane. This finding might represent a 'new sign' for congenital CMV infection in MRI examinations, being characteristic but nevertheless nonspecific, like calcification in CT. (orig.)

  20. Magnetic resonance imaging of the brain in congenital cytomegalovirus infection

    Energy Technology Data Exchange (ETDEWEB)

    Boesch, C.; Issakainen, J.; Kewitz, G.; Kikinis, R.; Martin, E.; Boltshauser, E.

    1989-01-01

    The children (age 2 months to 8 years) with a congenital cytomegalovirus (CMV) infection were studied by magnetic resonance imaging (MRI) using a 2.35 Tesla magnet. CMV infection was confirmed by serological investigations and virus culture in the neonatal period. Nine children had severe mental retardation and cerebral palsy, 1 patient suffered from microcephaly, ataxia and deafness. The cranial MRI examination showed the following abnormalities (N): Dilated lateral ventricles (10) and subarachnoid space (8), oligo/pacgyria (8), delayed/pathological myelination (7), paraventricular cysts (6), intra-cerebral calcification (1). This lack of sensitivity for calcification is explainable by the basic principles of MRI. The paraventricular cystic lesions were adjacent ot the occipital horns of the lateral ventricles and separated only by a thin membrane. This finding might represent a 'new sign' for congenital CMV infection in MRI examinations, being characteristic but nevertheless nonspecific, like calcification in CT.

  1. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review

    Directory of Open Access Journals (Sweden)

    Varbobitis Ioannis C

    2008-03-01

    Full Text Available Abstract Background The morbidity and mortality associated with cytomegalovirus (CMV infection in immunocompromised patients (especially in HIV-infected patients and transplant recipients, as well as with congenital CMV infection are well known. In contrast, relatively little attention has been paid to the morbidity and mortality that CMV infection may cause in immunocompetent patients. Methods We reviewed the evidence associated with severe manifestations of CMV infection in apparently immunocompetent patients and the potential role of antiviral treatment for these infections. We searched in PubMed, Scopus, and the Cochrane Library for the period of 1950–2007 to identify relevant articles. Results We retrieved 89 articles reporting on severe CMV infection in 290 immunocompetent adults. Among these reports, the gastrointestinal tract (colitis and the central nervous system (meningitis, encephalitis, transverse myelitis were the most frequent sites of severe CMV infection. Manifestations from other organ-systems included haematological disorders (haemolytic anaemia, thrombocytopenia, thrombosis of the venous or arterial vascular system, ocular involvement (uveitis, and lung disease (pneumonitis. The clinical practice reported in the literature has been to prescribe antiviral treatment for the most severe manifestations of monophasic meningoencephalitis (seizures and coma, ocular involvement, and lung involvement due to CMV. Conclusion Severe life-threatening complications of CMV infection in immunocompetent patients may not be as rare as previously thought.

  2. Cytomegalovirus-infected cells express Leu-M1 antigen. A potential source of diagnostic error.

    OpenAIRE

    Rushin, J. M.; Riordan, G. P.; Heaton, R. B.; Sharpe, R. W.; Cotelingam, J. D.; Jaffe, E S

    1990-01-01

    The authors examined cytomegalovirus (CMV)-infected tissues and Hodgkin's Disease (HD) cases with immunohistochemical assays for Leu-M1 and CMV. The cytologic characteristics were correlated with immunostaining patterns. Cytomegalovirus-infected cells in lymph node, lung, and esophagus sections showed Cowdry type A inclusions, and many had granular cytoplasmic inclusions. All infected cells showed nuclear staining with an anti-CMV antibody. Leu-M1 reacted with CMV-infected cells in cytoplasmi...

  3. Natural Killer Cell Evasion Is Essential for Infection by Rhesus Cytomegalovirus.

    Science.gov (United States)

    Sturgill, Elizabeth R; Malouli, Daniel; Hansen, Scott G; Burwitz, Benjamin J; Seo, Seongkyung; Schneider, Christine L; Womack, Jennie L; Verweij, Marieke C; Ventura, Abigail B; Bhusari, Amruta; Jeffries, Krystal M; Legasse, Alfred W; Axthelm, Michael K; Hudson, Amy W; Sacha, Jonah B; Picker, Louis J; Früh, Klaus

    2016-08-01

    The natural killer cell receptor NKG2D activates NK cells by engaging one of several ligands (NKG2DLs) belonging to either the MIC or ULBP families. Human cytomegalovirus (HCMV) UL16 and UL142 counteract this activation by retaining NKG2DLs and US18 and US20 act via lysomal degradation but the importance of NK cell evasion for infection is unknown. Since NKG2DLs are highly conserved in rhesus macaques, we characterized how NKG2DL interception by rhesus cytomegalovirus (RhCMV) impacts infection in vivo. Interestingly, RhCMV lacks homologs of UL16 and UL142 but instead employs Rh159, the homolog of UL148, to prevent NKG2DL surface expression. Rh159 resides in the endoplasmic reticulum and retains several NKG2DLs whereas UL148 does not interfere with NKG2DL expression. Deletion of Rh159 releases human and rhesus MIC proteins, but not ULBPs, from retention while increasing NK cell stimulation by infected cells. Importantly, RhCMV lacking Rh159 cannot infect CMV-naïve animals unless CD8+ cells, including NK cells, are depleted. However, infection can be rescued by replacing Rh159 with HCMV UL16 suggesting that Rh159 and UL16 perform similar functions in vivo. We therefore conclude that cytomegaloviral interference with NK cell activation is essential to establish but not to maintain chronic infection. PMID:27580123

  4. Toxic epidermal necrolysis associated with severe cytomegalovirus infection in a patient on regular hemodialysis

    OpenAIRE

    Khalaf, Dina; Toema, Bassem; Dabbour, Nidal; Jehani, Fathi

    2011-01-01

    Primary illness with cytomegalovirus leads to latent infection with possible reactivations especially in the immunocompromised patients. Toxic epidermal necrolysis is an immune mediated cytotoxic reaction. A fifty years old female diabetic hypertensive patient with end stage renal disease was admitted with fever of unknown origin, constitutional symptoms, vague upper gastrointestinal symptoms and skin rash. Upper gastrointestinal endoscopic biopsy confirmed her diagnosis with cytomegalovirus ...

  5. Acute ulcerative proctocolitis associated with primary cytomegalovirus infection.

    Science.gov (United States)

    Diepersloot, R J; Kroes, A C; Visser, W; Jiwa, N M; Rothbarth, P H

    1990-08-01

    The case is reported of a 39-year-old pregnant woman who presented with fever, abdominal complaints, and diarrhea. Laboratory investigation revealed mononucleosis in the peripheral blood. All microbiological studies were negative, with the exception of finding cytomegalovirus (CMV). Seroconversion was documented; the virus was cultured from urine and subsequently was demonstrated to be present in the inflamed mucosa of the rectum and distal sigmoid, which was found at sigmoidoscopy. This woman was delivered of a neonate with congenital CMV infection but without apparent malformations. The patient experienced recurrences of the bowel disease, in the first of which CMV could still be cultured from a biopsy specimen. In the follow-up period, an otherwise aspecific chronic inflammatory bowel disease remained present. No immunological abnormalities were found, and antibodies to human immunodeficiency virus were negative. This case demonstrates that inflammatory bowel disease can develop as a result of primary infection with CMV. PMID:2166491

  6. Neuro-imaging findings in infants with congenital cytomegalovirus infection : Relation to trimester of infection

    NARCIS (Netherlands)

    Oosterom, Natanja; Nijman, Joppe; Gunkel, Julia; Wolfs, Tom F W; Groenendaal, Floris; Verboon-Maciolek, Malgosia A.; De Vries, Linda S.

    2015-01-01

    Background: Congenital cytomegalovirus (cCMV) infection early in pregnancy may result in major disabilities. Cerebral abnormalities detected using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) have been related to neurological sequelae. Objective: To evaluate the additional value of

  7. Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

    Directory of Open Access Journals (Sweden)

    Mark R. Schleiss

    2013-01-01

    Full Text Available Fetal and neonatal infections caused by human cytomegalovirus (CMV are important causes of morbidity and occasional mortality. Development of a vaccine against congenital CMV infection is a major public health priority. Vaccine design is currently focused on strategies that aim to elicit neutralizing antibody and T-cell responses, toward the goal of preventing primary or recurrent infection in women of child-bearing age. However, there has been relatively little attention given to understanding the mechanisms of immune protection against acquisition of CMV infection in the fetus and newborn and how this information might be exploited for vaccine design. There has similarly been an insufficient study of what deficits in the immune response to CMV, both for mother and fetus, may increase susceptibility to congenital infection and disease. Protection of the fetus against vertical transmission can likely be achieved by protection of the placenta, which has its own unique immunological milieu, further complicating the analysis of the correlates of protective immunity. In this review, the current state of knowledge about immune effectors of protection against CMV in the maternal, placental, and fetal compartments is reviewed. A better understanding of immune responses that prevent and/or predispose to infection will help in the development of novel vaccine strategies.

  8. Cytomegalovirus infection following liver transplantation: review of the literature.

    Science.gov (United States)

    Kanj, S S; Sharara, A I; Clavien, P A; Hamilton, J D

    1996-03-01

    Cytomegalovirus (CMV) remains a major cause of problems following solid organ transplantation, accounting for a significant increase in morbidity and affiliated costs. Infection with CMV following orthotopic liver transplantation (OLT) is commonly seen as a result of marked cell-mediated immunosuppression and is an independent risk factor for opportunistic and fungal infections. The role of CMV infection in acute cellular or chronic rejection remains unclear. Recent advances in diagnostic modalities, particularly the use of the antigenemia assay and the polymerase chain reaction, have provided ways to quantitate viral load during infection or disease, as well as providing a useful marker of response to therapy. Ganciclovir remains the best antiviral agent for the treatment of CMV disease, but the use of combination therapy with other antivirals or CMV immunoglobulin may improve outcome for patients with severe disease. The ideal prophylactic therapy for patients undergoing OLT remains to be identified, as tested regimens have shown variable efficacy when analyzed with regard to defined risk groups. The use of risk group-specific prophylaxis may prove to be most successful, however, in terms of efficacy and cost savings. Future advances in basic CMV virology and transplant immunology will be essential in defining rational approaches to control and prevention of CMV infection and disease following liver transplantation. PMID:8852975

  9. Immune thrombocytopenic purpura secondary to cytomegalovirus infection: A case report.

    Directory of Open Access Journals (Sweden)

    Bessy S Flores Chang

    2015-11-01

    Full Text Available Immune Thrombocytopenic Purpura (ITP is defined as an acquired thrombocytopenia with antibodies detected against platelet surface antigens, and it is the most common form of thrombocytopenia in otherwise asymptomatic adults. ITP secondary to an underlying condition is a diagnosis of exclusion that is essential to establish for treatment efficacy. Secondary thrombocytopenia caused by Cytomegalovirus (CMV is common, however case reports associated with diagnosis in immunocompetent adults are rare, and to the best of our knowledge only 20 publications have been associated with this diagnosis. Our report is based on a clinical presentation of a 37 year old female complaining of petechiae, heavy menses, shortness of breath and a platelet count of 1 X 109 /L. Treatment with IVIG and steroids failed to improve platelet count. Subsequently, an infectious laboratory workup was performed, detecting CMV infection, and treatment with antiviral agents was initiated, causing platelet count to increase as viral load decreased.

  10. MENETRIER´S DISEASE ASSOCIATED WITH AN INFECTION BY CYTOMEGALOVIRUS

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    De Vivero-Camacho Rodrigo

    2015-12-01

    Full Text Available Introduction: Menetrier´s disease is rare in pediatrics. With no established etiology has been associated with viral and bacterial infections most of them able to generate an inflammatory process and protein-loosing with clinical abdominal pain, nausea, vomiting and edema, spontaneous resolution after 4-6 weeks without sequelae. The main objective is to describe a menetrier´s disease case in a male child in pediatric. Clinical case: a three years old male child without perinatal history, with clinical profile of five days with vomiting, abundant diarrhea, not dysentery, and fever, in the last two days with bipalpebral edema. After the cropology test the patient presented Giardia lamblia cysts, treated with metronidazole. The child is remitted to Hospital Infantil Napoleón Franco Pareja in Cartagena-Colombia, because of evidence of edema bipalpebral. In the emergency room male child presented good general condition with acute illness, stable vital signs, blood count with mild leukocytosis, blood smear with toxic granulations in neutrophils, partial urine without proteinuria, serum albumin 1.26 g../ dl. normal transaminases, normal serum electrolytes, normal lipid profile, ultrasound with distended bowel moderate, upper endoscopy with hypertrophy folds mucosa and gastric body, hyperemia and friability without erosions. The biopsy showed chronic active gastropathy with marked foveal hyperplasia compatible with Menetrier disease. During his hospitalization was administered albumin 1 g / kg for four days with resolution of edema and serum protein, the patient was discharged with normal albumin and subsequent controls and then he continued asymptomatic with complete resolution of the clinical disease. Conclusion: Menetrier´s disease in children is self-limiting with duration from 4 to 6 weeks; it can present abdominal pain, vomiting, nausea and edema. With the clinical and endoscopic findings of gastric folds hypertrophy can be presumed diagnosis

  11. Cytomegalovirus infection in immunosuppressed patients after kidney transplantation.

    Science.gov (United States)

    Luscalov, Simona; Loga, Luminita; Dican, Lucia; Junie, Lia Monica

    2016-01-01

    The first kidney transplantation was performed in 1951 and ever since then living donor transplantation became a more and more important solution for patients with end-stage renal disease (ESRD). Renal transplantation is a life-saving procedure. Morbidity and mortality on waiting-lists are strongly correlated with the time of dialysis and end-stage renal disease is one of the most important causes of death; this is the reason why transplantation has to be performed as soon as possible in order to reduce the time of dialysis. Once the transplantation is performed, a number of complications may occur in post-transplant evolution, the most important of which is rejection. The rejection may appear through several mechanisms, but one of the most frequent causes of rejection is cytomegalovirus (CMV) infection. It is very important to have a precocious and fast diagnosis of CMV infection in order to maintain the functionality and survival of the graft. PP65 CMV antigenemia has proven its effectiveness in detecting and monitoring the CMV infection in transplanted patients. In the laboratory of the Clinical Institute of Urology and Renal Transplantation (ICUTR) of Cluj Napoca the CMV infection is evidenced by two methods: PP65antigenemia and IgM antibody identification by chemiluminiscence. PMID:27547053

  12. Toxic epidermal necrolysis associated with severe cytomegalovirus infection in a patient on regular hemodialysis.

    Directory of Open Access Journals (Sweden)

    Dina Khalaf

    2011-01-01

    Full Text Available Primary illness with cytomegalovirus leads to latent infection with possible reactivations especially in the immunocompromised patients. Toxic epidermal necrolysis is an immune mediated cytotoxic reaction. A fifty years old female diabetic hypertensive patient with end stage renal disease was admitted with fever of unknown origin, constitutional symptoms, vague upper gastrointestinal symptoms and skin rash. Upper gastrointestinal endoscopic biopsy confirmed her diagnosis with cytomegalovirus esophagitis and duodenitis. Cytomegalovirus immunoglobulin M and immunoglobulin G levels were negative but polymerase chain reaction showed fulminant viremia. Biopsy of the skin rash was consistent with toxic epidermal necrolysis. Despite treatment with Ganciclovir, intravenous immunoglobulins, and granulocyte colony stimulating factor the patient’s condition rapidly deteriorated and she died due to multiorgan failure, disseminated intravascular coagulopathy and overwhelming sepsis. Probably there is a true association linking toxic epidermal necrolysis to fulminant reactivation of cytomegalovirus. The aim of this anecdote is reporting a newly recognized presentation of cytomegalovirus.

  13. Distribution of Cytomegalovirus Genotypes among Neonates Born to Infected Mothers in Islamabad, Pakistan

    Science.gov (United States)

    Mujtaba, Ghulam; Khurshid, Adnan; Sharif, Salmaan; Alam, Muhammad Masroor; Aamir, Uzma Bashir; Shaukat, Shahzad; Angez, Mehar; Rana, Muhammad Suleman; Umair, Massab; Shah, Aamer Ali; Zaidi, Syed Sohail Zahoor

    2016-01-01

    Background Congenital cytomegalovirus (cCMV) infection contributes to considerable long-term sequelae in neonates and children all over the world. The association between viral genotypes and severity of clinical cytomegalovirus (CMV) infection is yet to be defined. The objective of this study was to find the impact of active CMV infection during pregnancy and the clinical significance of genotypes in neonates with congenital cytomegalovirus infections in Pakistan. Methods A total of 409 blood samples from pregnant women seeking health care services at the two antenatal hospitals of Islamabad during January to December 2012 were tested by ELISA and nested-PCR. Pregnant women with active infection (detected as IgM positive, PCR positive or positive on both assays) were followed until delivery, to detect the outcome of overt cCMV infection in neonates. Genetic characterization of CMV strains was performed by sequence analysis of envelope glycoproteins: gB, gN and gH to detect the contributing CMV genotypes. Results The seroprevalence of anti-CMV IgG and IgM was 97.5% (399 out of 409) and 12.7% (52 out of 409), respectively, while 20% (82/409) pregnant women were found positive for CMV DNA by PCR. Logistic regression analysis showed a significant association of active infection with parity [OR = 2.56, 95% CI = 1.82–2.62, p = 0.04], febrile illness [OR = 1.84, 95% CI = 1.76–3.65, p = 0.01] and jaundice [OR = 22.5, 95% CI = 4.53–85.02, p = 0.002]. We were able to isolate virus in 41 out of 70 neonates; 36.6% (15 out of 41) of them were symptomatic at birth while 63.4% (26 out of 41) were asymptomatic. The most prominent clinical feature observed in symptomatic neonates was hepatosplenomegaly (26.6%; 4 out of 15). All three genotypes gB, gN and gH were found with the highest frequency of gB1 genotype, found in 75% infants with hepatic damage. Phylogenetic analysis of Pakistani strains showed 96%-100% homology to their prototype strains. Conclusions Active CMV

  14. Infection with cytomegalovirus is not associated with premature mortality

    Directory of Open Access Journals (Sweden)

    Stuart P. Adler

    2011-12-01

    Full Text Available Over 90% of the world’s population acquires a cytomegalovirus (CMV infection. This infection, although asymptomatic or self-limiting, is a major burden to the immune system. For this reason, and because CMV immunization is possible, determining whether CMV can cause reduced longevity, particularly among those with coronary artery disease, is important and previous reports have been conflicting. Thus our objective was to assess the association between CMV infection as defined serologically and antibody levels against CMV and longterm survival (18 years. We completed a prospective observational cohort study of 915 consecutive patients (mean age 58 years undergoing coronary angiography. CMV immunoglobulin levels were measured at baseline using either a whole cell CMV antigen or a purified protein antigen (gB. After adjustment for potentially confounding variables (age, race, gender, body mass index, the presence or absence of coronary artery disease, the number of diseased vessels, diabetes, renal disease, hypertension, dialysis, congestive heart failure, and the maximum percent reduction in luminal diameter, Cox’s proportional hazards models showed no association between CMV seropositivity or levels of antibodies against CMV by either assay and longevity for both patients with or without coronary artery disease (CAD nor for those under or over 70 years of age at baseline. Our observations suggest that universal immunization against CMV may not improve longevity.

  15. Case of Cytomegalovirus Infection Causing Isolated Oculomotor Nerve Palsy

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    Halil Sen

    2014-06-01

    Full Text Available The third cranial nerve is called the oculomotor nerve. The pathology is revealed by limitation of eye movement inward-up-down, mydriasis, loss of light reflex and ptosis. Oculomotor nerve pathologies are frequently seen in neurology practice and are situations that may be very difficult for differential diagnosis. Differential diagnosis first involves disqualifying intracranial etiologies by imaging because these intracranial etiologies may be situations that can result in death and should be primarily evaluated. If intracranial events are ruled out, generally rarer etiologic reasons with generally difficult differentiation should be researched. Viral infections are among the rare etiological reasons causing 3rd cranial nerve involvement. Our case was a 71-year old female with etiological research due to 3rd cranial nerve palsy. The patient with diabetes-linked immune deficiency was found to have cranial nerve involvement developed secondary to cytomegalovirus (CMV infection. We report this case as 3rd cranial nerve involvement is rarely observed developing linked to CMV infection.

  16. Sclerosing cholangitis by cytomegalovirus in highly active antiretroviral therapy era

    Directory of Open Access Journals (Sweden)

    Carmen Hidalgo-Tenorio

    2013-10-01

    Full Text Available Sclerosing colangitis (SC due to cytomegalovirus (CMV is very rare. It has been described mainly in immunocompromised patients. Currently, in HIV infected patients it is exceptional. The most of cases belong to pre-highly active antiretroviral therapy (pre-HAART and those cases were in stage AIDS with less than 100 CD4/μl. The most frequently involved pathogen in pre-HAART period was Cryptosporidium parvum (30-57% and CMV (10-30%; in late HAART period this information are unaware. CMV has been implicated as a possible etiological agent in primary SC partly because of the ability to cause liver damage and its relationship with smooth muscle antibodies. The most effective treatment for SC was the combination of antiretroviral therapy and endoscopic retrograde cholangiopancreatography with sphincterotomy and stent placement. Following, we present the first case of late HAART period which describes a SC extrahepatic without papillary stenosis with CMV as the only cause and clinical presentation of HIV infection in a woman with 177 CD4/μl.

  17. Cytomegalovirus infection enhances the immune response to influenza.

    Science.gov (United States)

    Furman, David; Jojic, Vladimir; Sharma, Shalini; Shen-Orr, Shai S; Angel, Cesar J L; Onengut-Gumuscu, Suna; Kidd, Brian A; Maecker, Holden T; Concannon, Patrick; Dekker, Cornelia L; Thomas, Paul G; Davis, Mark M

    2015-04-01

    Cytomegalovirus (CMV) is a β-herpesvirus present in a latent form in most people worldwide. In immunosuppressed individuals, CMV can reactivate and cause serious clinical complications, but the effect of the latent state on healthy people remains elusive. We undertook a systems approach to understand the differences between seropositive and negative subjects and measured hundreds of immune system components from blood samples including cytokines and chemokines, immune cell phenotyping, gene expression, ex vivo cell responses to cytokine stimuli, and the antibody response to seasonal influenza vaccination. As expected, we found decreased responses to vaccination and an overall down-regulation of immune components in aged individuals regardless of CMV status. In contrast, CMV-seropositive young adults exhibited enhanced antibody responses to influenza vaccination, increased CD8(+) T cell sensitivity, and elevated levels of circulating interferon-γ compared to seronegative individuals. Experiments with young mice infected with murine CMV also showed significant protection from an influenza virus challenge compared with uninfected animals, although this effect declined with time. These data show that CMV and its murine equivalent can have a beneficial effect on the immune response of young, healthy individuals, which may explain the ubiquity of CMV infection in humans and many other species. PMID:25834109

  18. [Giant gastric ulcer by cytomegalovirus in infection VIH/SIDA].

    Science.gov (United States)

    Pérez-Pereyra, Julia; Morales, Domingo; Díaz, Ramiro; Yoza, Max; Frisancho, Oscar

    2008-01-01

    Cytomegalovirus infection is an important cause of morbidity in immunosupressed patients with Human Immunodeficiency Virus (HIV). In this paper we present a 43 years old man with renal failure under hemodialysis, several blood transfusions because of anemia and three months of disease characterized by epigastric pain, specially at nights, ameliorated with antacid drugs. Other symptoms were early satisfy, vomits and weigh loss (18Kg). At clinical exam, the patient was pallid, presented adenopathies at cervical and inguinal regions and had a pain at epigastric region in profound touch palpation. The most important exams were HB: 10mg/dl, CMV: 83.5, leukocytes 7000, lymphocytes: 1715, erythrocyte sedimentation rate 49mm/h, the venon test (-), and Giardia lamblia trophozoites in stools. The studies demonstrated the patient was seropositive for HIV and the tests for IgG CMV and IgG Herpes virus resulted seropositives too. At endoscopy the esophagus mucosa was covered by a white plaque which suggests candida infection. In the stomach, over the body gastric, we found a big and deep ulcerated lesion (45 x 41mm), with defined rims and white fund. Biopsy from the edges of the gastric ulcer had the characteristic CMV intranuclear and intracytoplasmic inclusions; we confirmed the diagnosis by immunohystochemistry. The patient receives ganciclovir an then HAART and is getting well.

  19. Transplacental murine cytomegalovirus infection in the brain of SCID mice

    Directory of Open Access Journals (Sweden)

    Jaquish Dawn V

    2007-03-01

    Full Text Available Abstract Background Congenital cytomegalovirus (CMV infection is the most common congenital viral infection in humans and the major nonhereditary cause of central nervous system (CNS developmental disorders. Previous attempts to develop a murine CMV (MCMV model of natural congenital human CMV (HCMV infection have failed because MCMV does not cross the placenta in immunocompetent mice. Results In marked contrast with immunocompetent mice, C.B-17 SCID (severe combined immunodeficient mice were found to be highly susceptible to natural MCMV transplacental transmission and congenital infection. Timed-pregnant SCID mice were intraperitoneally (IP injected with MCMV at embryonic (E stages E0-E7, and vertical MCMV transmission was evaluated using nested polymerase chain reaction (nPCR, in situ hybridization (ISH and immunohistochemical (IHC assays. SCID mouse dams IP injected at E0 with 102 PFU of MCMV died or resorbed their fetuses by E18. Viable fetuses collected at E18 from SCID mice IP injected with 102–104 PFU of MCMV at E7 did not demonstrate vertical MCMV transmission. Notably, transplacental MCMV transmission was confirmed in E18 fetuses from SCID mice IP injected with 103 PFU of MCMV at stages E3-E5. The maximum rate of transplacental MCMV transmission (53% at E18 occurred when SCID mouse dams were IP injected with 103 PFU of MCMV at E4. Congenital infection was confirmed by IHC immunostaining of MCMV antigens in 26% of the MCMV nPCR positive E18 fetuses. Transplacental MCMV transmission was associated with intrauterine growth retardation and microcephaly. Additionally, E18 fetuses with MCMV nPCR positive brains had cerebral interleukin-1α (IL-1α expression significantly upregulated and cerebral IL-1 receptor II (IL-1RII transcription significantly downregulated. However, MCMV-induced changes in cerebral cytokine expression were not associated with any histological signs of MCMV infection or inflammation in the brain. Conclusion Severe T

  20. Effects of Murine Cytomegalovirus Infection on Sperm Viability in Mice

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to explore the effects of testicular infection of murine cytomegalovirus (MCMV) on mature sperm viability at different periods following MCMV inoculation in mice, 91 BALB/c mice without MCMV infection were randomly divided into two groups: an experimental group (n=56) and a control group (n= 35). The mice in the experimental group were treated by inoculating MCMV intratesticularly, while those in the controlled group were directly inoculated with DMEM without MCMV. The mice in both groups were sacrificed separately on the day 1,1.5, 2, 4, 6, 9 and 14 post-inoculation (D1, 1.5,2, 4, 6, 9 and 14 PI). The MCMV M83 mRNA gene was detected in the testis by in situ hybridization (ISH) with MCMV late-mRNA probe labeled with digoxin.Sperm viability of mature sperm in the epididymis cauda was measured. The results demonstrated the positive signal of ISH of MCMV was found mainly in the cytoplasm of the testicular interstitial cells and spermatogenic cells in the experimental group. Compared with that in the controlled group, the sperm viability in the experimental group was decreased significantly on D1 PI and D1.5PI (P< 0.05). No statistically significant difference in the sperm viability was found after D2 PI between two groups (P>0.05). This suggested that sperm viability in mice might be descended significantly shortly after MCMV infection and might return to normal with time, indicating that MCMV acute infection might temporarily degrade sperm quality and influence procreation transiently.

  1. Factors associated with the development of cytomegalovirus infection following solid organ transplantation

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Sørensen, Søren S; Iversen, Martin;

    2011-01-01

    Infection with cytomegalovirus (CMV) remains a potentially serious complication in transplant patients. In this study we explored the risk factors for CMV infection in the 12 months following a solid organ transplantation (n = 242) in patients monitored for CMV infection from 2004 to 2007....

  2. DIAGNOSIS OF CONGENITAL CYTOMEGALOVIRUS INFECTION IN HIGH RISK NEONATES

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    Ehab abdelmoniem Albanna

    2013-07-01

    Full Text Available Objectives: This study aimed to compare polymerase chain reaction (PCR and IgM detection using enzyme linked immune-sorbent assay (ELISA in diagnosis of congenital cytomegalovirus (CMV infection.   Methods: This study was conducted from May 2009 to December 2010. Urine and blood samples were collected from 94 neonates with suspected congenital CMV infection. Serum and part of urine samples were stored at -20°C freezer, until the serologic and PCR tests were achieved. A 94 fresh urine samples were processed for cell culture. Nineteen (20.2% out of 94 urine samples were proven positive for CMV infection by viral culture. For comparing PCR and IgM ELISA we used tissue culture technique as a reference, the 19 positive samples on culture (CMV group and 20 negative samples (control group were included in the comparison. Some characteristics of CMV and control groups were compared including sex, age, birth weight, gestational age < 37 and small for gestational age. Clinical and laboratory abnormalities were also compared in both groups.   Results: This study showed that the sensitivity and specificity of PCR in relation to viral culture were 100% and 100% respectively, there was excellent agreement between both tests (Kappa coefficient was 1 and P=0.000. On the other hand, the sensitivity of IgM CMV ELISA in relation to viral culture was 63.2% and the specificity was 85%. There was good agreement between both tests (Kappa coefficient was 0.48 and P=0.002. By comparing CMV and control groups, there were high statistically significant differences between both groups as regard the birth weight, gestational age < 37 and small for gestational age items (P= 0.00, 0.03 and 0.01 respectively. There were statistically insignificant differences as regarding the clinical and laboratory abnormalities detected for neonates of both groups. In this study jaundice (63% and hepato-splenomegaly (42% were the most common clinical signs in both groups.   Conclusion

  3. Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway.

    Directory of Open Access Journals (Sweden)

    Magdalena Angelova

    Full Text Available Human Cytomegalovirus (HCMV is a ubiquitous herpesvirus that currently infects a large percentage of the world population. Although usually asymptomatic in healthy individuals, HCMV infection during pregnancy may cause spontaneous abortions, premature delivery, or permanent neurological disabilities in infants infected in utero. During infection, the virus exerts control over a multitude of host signaling pathways. Wnt/β-catenin signaling, an essential pathway involved in cell cycle control, differentiation, embryonic development, placentation and metastasis, is frequently dysregulated by viruses. How HCMV infection affects this critical pathway is not currently known. In this study, we demonstrate that HCMV dysregulates Wnt/β-catenin signaling in dermal fibroblasts and human placental extravillous trophoblasts. Infection inhibits Wnt-induced transcriptional activity of β-catenin and expression of β-catenin target genes in these cells. HCMV infection leads to β-catenin protein accumulation in a discrete juxtanuclear region. Levels of β-catenin in membrane-associated and cytosolic pools, as well as nuclear β-catenin, are reduced after infection; while transcription of the β-catenin gene is unchanged, suggesting enhanced degradation. Given the critical role of Wnt/β-catenin signaling in cellular processes, these findings represent a novel and important mechanism whereby HCMV disrupts normal cellular function.

  4. Uninfected and cytomegalic endothelial cells in blood during cytomegalovirus infection : Effect of acute rejection

    NARCIS (Netherlands)

    Kas-Deelen, AM; de Maar, EF; Harmsen, MC; van Son, WJ; The, TH; Driessen, C.

    2000-01-01

    After transplantation, human cytomegalovirus (HCMV) infections can cause vascular damage to both the graft and the host. To study a possible relationship between the degree of vascular injury, clinical symptoms of HCMV infection, and transplant rejection, the appearance and numbers of endothelial ce

  5. AABB Committee Report: reducing transfusion-transmitted cytomegalovirus infections.

    Science.gov (United States)

    Heddle, Nancy M; Boeckh, Michael; Grossman, Brenda; Jacobson, Jessica; Kleinman, Steven; Tobian, Aaron A R; Webert, Kathryn; Wong, Edward C C; Roback, John D

    2016-06-01

    Transfusion-transmitted cytomegalovirus (TT-CMV) is often asymptomatic, but certain patient populations, such as very low birth weight neonates, fetuses requiring intrauterine transfusion, pregnant women, patients with primary immunodeficiencies, transplant recipients, and patients receiving chemotherapy or transplantation for malignant disease, may be at risk of life-threatening CMV infection. It is unclear whether leukoreduction of cellular blood components is sufficient to reduce TT-CMV or whether CMV serological testing adds additional benefit to leukoreduction. The AABB CMV Prevention Work Group commissioned a systematic review to address these issues and subsequently develop clinical practice guidelines. However, the data were of poor quality, and no studies of significant size have been performed for over a decade. Rather than creating guidelines of questionable utility, the Work Group (with approval of the AABB Board of Directors) voted to prepare this Committee Report. There is wide variation in practices of using leukoreduced components alone or combining CMV-serology and leukoreduction to prevent TT-CMV for at-risk patients. Other approaches may also be feasible to prevent TT-CMV, including plasma nucleic acid testing, pathogen inactivation, and patient blood management programs to reduce the frequency of inappropriate transfusions. It is unlikely that future large-scale clinical trials will be performed to determine whether leukoreduction, CMV-serology, or a combination of both is superior. Consequently, alternative strategies including pragmatic randomized controlled trials, registries, and collaborations for electronic data merging, nontraditional approaches to inform evidence, or development of a systematic approach to inform expert opinion may help to address the issue of CMV-safe blood components. PMID:26968400

  6. Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan

    Institute of Scientific and Technical Information of China (English)

    Masaaki Minami; Michio Ohta; Teruko Ohkura; Takafumi Ando; Naoki Ohmiya; Yasumasa Niwa; Hidemi Goto

    2007-01-01

    AIM: To investigate active cytomegalovirus (CMV) infection following the cyclosporine A (CyA) treatment of steroid-refractory ulcerative colitis (UC).METHODS: Twenty-three patients with severe UC not responding to steroid therapy (male 14, and female 9)enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA (average 4 mg/kg per day) for 1 mo. Serum and colonic biopsy samples were collected before CyAtreatment and 4 d, 10 d, 20 d, and 30 d after treatment.Patients were evaluated for CMV by using serology (IgM antibody by ELISA), quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin (HE)-stained colonic biopsies. CMV infection was indicated by positive results in any test.RESULTS: No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV (IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients,78.2%; and inclusion bodies in 4/23 patients, 17.3%).There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment,leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection (83.3%) required surgical treatment because of severe deteriorating colitis.Treatment with ganciclovir rendered surgery avoidable inthree patients.CONCLUSION: Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immunosuppressive therapy.

  7. Clinical Manifestations of Cytomegalovirus-Associated Posterior Uveitis and Panuveitis in Patients Without Human Immunodeficiency Virus Infection

    NARCIS (Netherlands)

    Pathanapitoon, Kessara; Tesavibul, Nattaporn; Choopong, Pitipol; Boonsopon, Sutasinee; Kongyai, Natedao; Ausayakhun, Somsanguan; Kunavisarut, Paradee; Rothova, Aniki

    2013-01-01

    Importance: Little attention has been paid to clinical features of cytomegalovirus (CMV) infections in individuals without human immunodeficiency virus (HIV). Objective: To describe the clinical manifestations and comorbidities of patients without HIV infection who have CMV-associated posterior uvei

  8. Cytomegalovirus infection after liver transplantation: Current concepts and challenges

    Institute of Scientific and Technical Information of China (English)

    Raymund Rabe Razonable

    2008-01-01

    Cytomegalovirus(CMV)is a common viral pathogen that influences the outcome of liver transplantation.In addition to the direct effects of CMV syndrome and tissue-invasive diseases,CMV is associated with an increased predisposition to acute and chronic allograft rejection,accelerated hepatitis C recurrence,and other opportunistic infections,as well as reduced overall patient and allograft survival.Risk factors for CMV disease are often interrelated,and include CMV D+/R-serostatus,acute rejection,female gender,age,use of high-dose mycophenolate mofetil and prednisone,and the overall state of immunity.In addition to the role of CHV-specific CD4+ and CD8+ T lymphocytes,there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis.In one study,liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher Ievels of CMV replication and clinical disease.Because of the direct and indirect adverse effects of CMV disease,its prevention,whether through antiviral prophylaxis or preemptive therapy,is an essential component in improving the outcome of liver transplantation.In the majority of transplant centers,antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-).However,the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease.In several prospective and retrospective studies,the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation.Therefore,optimized strategies for prevention and novel drugs with unique modes of action are needed.Currently,a randomized controlled clinical trial is being

  9. Transient Antiphospholipid Syndrome Associated with Primary Cytomegalovirus Infection: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Nakayama

    2014-01-01

    Full Text Available Viral infection is known to induce transient autoimmunity in humans. Acute cytomegalovirus (CMV infection is implicated in occasional thrombosis formation. We here, for the first time, report a 19-year-old female who had an acute CMV infection, leading to a deep venous thrombosis and a pulmonary embolism along with transient appearance of lupus anticoagulant. The pathological role of antiphospholipid antibodies in CMV-mediated thrombosis is discussed.

  10. Neck stiffness in Guillaine-Barre syndrome subsequent to cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    İbrahim Etem Pişkin

    2011-03-01

    Full Text Available Guillain-Barre syndrome is an acute inflammatory demyelinating polyradiculoneuropathy that can be seen at any age. The classic symptoms such as flaccid paralysis and areflexia are not always predominant in children. In this study, we presented a 3-year-old girl with Guillain-Barre syndrome associated with cytomegalovirus infection who referred with showed atypical symptoms including neck stiffness.

  11. Investigation of the Role of the Cytomegalovirus as a Respiratory Pathogen in HIV-Infected Patients

    Directory of Open Access Journals (Sweden)

    Rafael E de la Hoz

    1996-01-01

    Full Text Available OBJECTIVE: To investigate the occurrence of cytomegalovirus (CMV pneumonitis in the setting of human immunodeficiency virus (HIV infection and whether the presence of CMV as copathogen is associated with increased clinical severity or short term mortality in patients with Pneumocystis carinii pneumonia.

  12. The time course of development and impact from viral resistance against ganciclovir in cytomegalovirus infection

    DEFF Research Database (Denmark)

    Cunha-Bang, C da; Kirkby, N; Sønderholm, M;

    2013-01-01

    (Val)ganciclovir is used to treat cytomegalovirus (CMV) infection following solid organ (SOT) or hematopoietic stem cell (HSCT) transplantation. Treatment failures occur, but the contribution from 39 known ganciclovir-related mutations (GRMs) in the CMV-UL97 gene remains controversial. We propose...

  13. Inflammatory bowel disease after liver transplantation : a role for cytomegalovirus infection

    NARCIS (Netherlands)

    Verdonk, Robert C; Haagsma, Elizabeth B; Van Den Berg, Aad P; Karrenbeld, Arend; Slooff, Maarten J H; Kleibeuker, Jan H; Dijkstra, Gerard

    2006-01-01

    OBJECTIVE: Despite the use of immunosuppressive drugs, recurrent and de novo inflammatory bowel disease (IBD) can develop after orthotopic liver transplantation (OLT). Cytomegalovirus (CMV) infection has been suggested to play a role in the pathogenesis of IBD. The aim of this study was to investiga

  14. Severe rhabdomyolysis associated with a primary cytomegalovirus infection in an immunocompetent patient

    OpenAIRE

    Gindre, Héloïse; Féasson, Léonard; Auboyer, Christian; Cathébras, Pascal

    2013-01-01

    Virus-induced rhabdomyolysis rarely induces respiratory failure. We discuss here a case of severe rhabdomyolysis with acute respiratory failure secondary to a cytomegalovirus (CMV) primary infection. We report a case of severe acute rhabdomyolysis, leading to respiratory failure and mechanical ventilation, associated with CMV primary infection in a young and otherwise healthy woman. We excluded other aetiologies such as metabolic myopathies, electrolyte disorders or Guillain-Barré syndrome wi...

  15. Human Cytomegalovirus Infection Enhances NF-κB/p65 Signaling in Inflammatory Breast Cancer Patients

    OpenAIRE

    Mohamed El-Shinawi; Hossam Taha Mohamed; El-Ghonaimy, Eslam A.; Marwa Tantawy; Amal Younis; Schneider, Robert J.; Mona Mostafa Mohamed

    2013-01-01

    Human Cytomegalovirus (HCMV) is an endemic herpes virus that re-emerges in cancer patients enhancing oncogenic potential. Recent studies have shown that HCMV infection is associated with certain types of cancer morbidity such as glioblastoma. Although HCMV has been detected in breast cancer tissues, its role, if any, in the etiology of specific forms of breast cancer has not been investigated. In the present study we investigated the presence of HCMV infection in inflammatory breast cancer (I...

  16. Dendritic cell biology in human cytomegalovirus infection and the clinical consequences for host immunity and pathology

    OpenAIRE

    Gredmark-Russ, Sara; Söderberg-Nauclér, Cecilia

    2012-01-01

    Human cytomegalovirus (HCMV), a member of the herpesvirus family, establishes life-long persistence and latency after primary infection and can be reactivated later in life. In immunosuppressed patients, it is an important pathogen that can cause severe disease. HCMV is also thought to play a causative role in inflammatory diseases and cancer. The virus can infect different immune cells, including dendritic cells (DCs) and can take advantage of host immune functions to avoid immune recognitio...

  17. Human cytomegalovirus infection enhances NF-κB/p65 signaling in inflammatory breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Mohamed El-Shinawi

    Full Text Available Human Cytomegalovirus (HCMV is an endemic herpes virus that re-emerges in cancer patients enhancing oncogenic potential. Recent studies have shown that HCMV infection is associated with certain types of cancer morbidity such as glioblastoma. Although HCMV has been detected in breast cancer tissues, its role, if any, in the etiology of specific forms of breast cancer has not been investigated. In the present study we investigated the presence of HCMV infection in inflammatory breast cancer (IBC, a rapidly progressing form of breast cancer characterized by specific molecular signature. We screened for anti-CMV IgG antibodies in peripheral blood of 49 non-IBC invasive ductal carcinoma (IDC and 28 IBC patients. In addition, we screened for HCMV-DNA in postsurgical cancer and non-cancer breast tissues of non-IBC and IBC patients. We also tested whether HCMV infection can modulate the expression and activation of transcriptional factor NF-κB/p65, a hallmark of IBC. Our results reveal that IBC patients are characterized by a statistically significant increase in HCMV IgG antibody titers compared to non-IBC patients. HCMV-DNA was significantly detected in cancer tissues than in the adjacent non-carcinoma tissues of IBC and IDC, and IBC cancer tissues were significantly more infected with HCMV-DNA compared to IDC. Further, HCMV sequence analysis detected different HCMV strains in IBC patients tissues, but not in the IDC specimens. Moreover, HCMV-infected IBC cancer tissues were found to be enhanced in NF-κB/p65 signaling compared to non-IBC patients. The present results demonstrated a correlation between HCMV infection and IBC. Etiology and causality of HCMV infection with IBC now needs to be rigorously examined.

  18. Intrinsic Contribution of Perforin to NK-Cell Homeostasis during Mouse Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Maja eArapovic

    2016-04-01

    Full Text Available In addition to their role as effector cells in virus control, natural killer (NK cells have an immunoregulatory function in shaping the antiviral T-cell response. This function is further pronounced in perforin-deficient mice that show the enhanced NK-cell proliferation and cytokine secretion upon mouse cytomegalovirus (MCMV infection. Here we confirmed that stronger activation and maturation of NK cells in perforin-deficient mice correlates with higher MCMV load. To further characterize the immunoregulatory potential of perforin, we compared the response of NK cells that express or do not express perforin using bone-marrow chimeras. Our results demonstrated that the enhanced proliferation and maturation of NK cells in MCMV-infected bone-marrow chimeras is an intrinsic property of perforin-deficient NK cells. Thus, in addition to confirming that NK-cell proliferation is virus load dependent, our data extend this notion demonstrating that perforin plays an intrinsic role as a feedback mechanism in regulation of NK-cell proliferation during viral infections.

  19. Bronchial atresia in a neonate with congenital cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Abdullah A Yousef

    2013-01-01

    Full Text Available Bronchial atresia (BA is characterized by a mucus-filled bronchocele in a blind-ending segmental or lobar bronchus with hyperinflation of the obstructed segment of the lung. We describe a neonate who presented on his 9 th day of life with respiratory distress. Chest computed tomography showed a soft tissue density involving the right middle lobe (RML. RML lobectomy confirmed the diagnosis of BA. Cytomegalovirus was detected by polymerase chain reaction in blood, urine, and tracheal aspirates which may provide further insight into the pathogenesis of BA.

  20. The association of killer cell immunoglobulin like receptor gene polylmorphism with cytomegalovirus infection after hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    吴小津

    2013-01-01

    Objective To explore the influence of the killer cell immunoglobulin like receptor(KIR)gene polymorphism on cytomegalovirus(CMV)infection and pathogenesis after hematopoietic stem cell transplantation(HSCT)

  1. Massive alimentary tract bleeding due to cytomegalovirus infection in an elderly patient

    Directory of Open Access Journals (Sweden)

    Bora Koc

    2014-09-01

    Full Text Available In recent years, cytomegalovirus (CMV has been recognized as an important common pathogen in immunocompromized patients. This is due to the increasing number of immunosuppressive medications, intensive cancer chemotherapy use, recurrent transplantations, progressively aging population, and the higher number of human immunodeficiency virus infections. Cytomegalovirus infection especially interests the gastrointestinal tract, anywhere, from the mouth to the anus. Namely, the most commonly affected area is the colon, followed by duodenum, stomach, esophagus and small intestine. The most frequent manifestations of CMV colitis are: diarrhea, fever, gastrointestinal bleeding and abdominal pain. We report here the case of an 82-year-old woman, who was treated for non-Hodgkin lymphoma; she was admitted to the emergency department for abdominal pain and diffuse arthralgia, following massive upper- and lower- gastrointestinal bleeding, due to duodenal and colonic ulcers related to CMV infection.

  2. Massive Alimentary Tract Bleeding due to Cytomegalovirus Infection in an Elderly Patient.

    Science.gov (United States)

    Koc, Bora; Bircan, Huseyin Yuce; Altaner, Semsi; Cinar, Ozlem; Ozcelik, Umit; Yavuz, Alpaslan; Kemik, Ozgur

    2014-08-13

    In recent years, cytomegalovirus (CMV) has been recognized as an important common pathogen in immunocompromized patients. This is due to the increasing number of immunosuppressive medications, intensive cancer chemotherapy use, recurrent transplantations, progressively aging population, and the higher number of human immunodeficiency virus infections. Cytomegalovirus infection especially interests the gastrointestinal tract, anywhere, from the mouth to the anus. Namely, the most commonly affected area is the colon, followed by duodenum, stomach, esophagus and small intestine. The most frequent manifestations of CMV colitis are: diarrhea, fever, gastrointestinal bleeding and abdominal pain. We report here the case of an 82-year-old woman, who was treated for non-Hodgkin lymphoma; she was admitted to the emergency department for abdominal pain and diffuse arthralgia, following massive upper- and lower- gastrointestinal bleeding, due to duodenal and colonic ulcers related to CMV infection. PMID:25276331

  3. Fatal congenital cytomegalovirus infection following recurrent maternal infection after a 7-year interval

    International Nuclear Information System (INIS)

    It is generally accepted that the risk for fetal infection is greatest with maternal primary cytomegalovirus (CMV) infection and much less likely with recurrent infection. Here, we report a fatal case of congenital CMV infection following recurrent maternal infectious after a 7-year interval. A 3-months-old female baby presented with fever, jaundice, vomiting and stopping breast-feeding. Physical examination revealed mild respiratory distress, hepatosplenomegaly, microcephaly and growth retardation. Laboratory examination included bilirubin concentrations (total 7.17 mg/dl; conjugated 6.67 mg/dl), aspartate transaminase (141 IU), and alanine transminase (141 IU), and alanine transminase (499 IU). Enzyme linked immunosorbent assay test results revealed (+) CMV IgM and (+) CMV IgG. She died on the 10 th day of admission with the diagnosis of CMV hepatitis, pneumonia and multi-organ failure. Nuclear and cytoplasmic inclusions demonstrated in the lung, liver and brain on postmortem biopsy. This case highlights that the outcome of babies born to mothers with recurrent maternal CMV infection may be more severe and fatal than previously thought. (author)

  4. Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

    Science.gov (United States)

    Avery, R K; Bolwell, B J; Yen-Lieberman, B; Lurain, N; Waldman, W J; Longworth, D L; Taege, A J; Mossad, S B; Kohn, D; Long, J R; Curtis, J; Kalaycio, M; Pohlman, B; Williams, J W

    2004-12-01

    Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined. PMID:15489872

  5. Protein-losing enteropathy in a child with cytomegalovirus infection confirmed by 99mTc-HSA scintigraphy

    International Nuclear Information System (INIS)

    Protein-losing enteropathy, resulting from increased permeability of intestinal wall for plasma proteins may occur in a form of primary enteropathy or accompanies other diseases, mostly of the gastrointestinal tract. Only few cases could be found in literature on children with cytomegalovirus (CMV) infection in whom oedema and hypoproteinaemia, caused by the protein-losing enteropathy, and sometimes hypertrophic gastritis (Menetrier syndrome) were discussed. We present a case of scintigraphic imaging of such a syndrome in a 3.5 year old girl infected with cytomegalovirus. On scintigrams obtained 24 hours after i.v. administration of 74 MBq of 99mTc-labelled human serum albumin (99mTc-HSA ), a concentrated radioactivity was demonstrated in the ascending colon, although early imaging (up to 4 hours post injection) did not demonstrate unusual activity in the bowel. Suggestion is to be found that changes in the gastrointestinal tract could be caused by CMV infection. In our case for the first time scintigraphic imaging has been used to detect exsudative enteropathy in a child with CMV infection. (author)

  6. [Diagnosis of congenital cytomegalovirus infection in newborn dried blood spots on Guthrie cards. A promissory technique].

    Science.gov (United States)

    Distéfano, Angélica L; González, Cecilia A; Pardón, Fabián; Sarubi, María A; Canero Velazco, Cristina

    2008-04-01

    Laboratories play a crucial role in the diagnosis of congenital and perinatal cytomegalovirus infection, considering that other viral infections in newborn infants have similar clinical characteristics. The objectives of this work are to compare the results of the polymerase reaction in blood spots and urine as well as point out the relevance of the result in the Guthrie cards to differentiate congenital from perinatal infection. A total of 148 patients suspicious of CMVH infections were studied in the Congenital Perinatal Infections and Sexual Transmission Laboratory, at the National Institute "Carlos G. Malbrán". The dry blood samples (Guthrie cards) and urine of all patients were studied through the polymerase chain reaction. From the 148 patients, 3 presented other infections, 95 tested negative and 50 positive for cytomegalovirus: 35 had congenital infection and 15 perinatal. In the congenital cases, the polymerase reaction in dry blood was positive (sensitivity 100%, specificity 98.9%, VPP 98% and VPN 100%). Four of them with tardive symptoms were studied retrospectively. The urine specimens from the remaining 15 patients that were taken 15 days after birth were analyzed through the same methods, showing a sensitivity of 100%, the retrospective analysis of this dry blood group yielded negative results, so the infection was considered perinatal. Thus, the dry blood polymerase reaction of the newborn infants makes it a reliable assay for diagnosing congenital cytomegalovirus infection and could be used as an alternative method to urine polymerase reaction. In addition, this test is able to reveal whether the infection is congenital or perinatal in those cases of late symptom or other cases of controversial origin.

  7. Cytomegalovirus Infection and Coronary Artery Disease: A Single-Center Serological Study in Northwestern Iran

    OpenAIRE

    Zakieh Rostamzadeh Khameneh; Alireza Rostamzadeh; Mohaddeseh Nemati; Brown, Paul M.; Nariman Sepehrvand

    2016-01-01

    Background: The role of chronic Cytomegalovirus (CMV) infection and inflammation in the pathogenesis of atherosclerosis and Coronary Artery Disease (CAD) is still not clear. Objectives: This study aimed to explore the seroprevalence of anti-CMV antibodies and inflammatory markers in patients with stable angina who had undergone diagnostic coronary angiography for clinical suspicion of CAD. Patients and Methods: This cross-sectional, descriptive study was conducted on 181 patients with...

  8. Effect of Human Cytomegalovirus Infection on Nerve Growth Factor Expression in Human Glioma U251 Cells

    Institute of Scientific and Technical Information of China (English)

    HAI-TAO WANG; BIN WANG; ZHI-JUN LIU; ZHI-QIANG BAI; LING LI; HAI-YAN LIU; DONG-MENG QIAN; ZHI-YONG YAN; XU-XIA SONG

    2009-01-01

    Objectives To explore the change of endogenic nerve growth factor (NGF) expression in human glioma cells infected with human cytomegalovirus (HCMV). Methods U251 cells were cultured in RPMI 1640 culture medium and infected with HCMV AD169 strain in vitro to establish a cell model of viral infection. Morphologic changes of U251 cells were observed under inverted microscope before and after infection with HCMV. Expression of NGF gene and protein of cells was detected by RT-PCR and Western blotting before and after infection with HCMV. Results The cytopathic effects of HCMV-infected cells appeared on day 5 after infection. However, differential NGF expression was evident on day 7. NGF expression was decreased significantly in U251 cells on day 7 after infection in comparison with control group (P<0.05). Conclusion HCMV can down-regulate endogenous NGF levels in human glioma cell line U251.

  9. Severe cytomegalovirus infections in immunocompetent patients at admission as dengue mimic:Successful treatment with intravenous ganciclovir

    Institute of Scientific and Technical Information of China (English)

    Suhasini Tirumala; Bijayini Behera; Shilpa Lingala; B.Vijay Kumar; Pradeep Kumar Mishra; Gurunath JM; HariCharan; Kartik; Naresh

    2012-01-01

    Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons. The incidence and association of CMV reactivation with adverse clinical outcomes in critically ill persons lacking evidence of immunosuppression at ICU admission has received great attention in the practice of critical care medicine. Critically ill patients in ICU who had associated risk factors such as mechanical ventilation, severe sepsis, or blood transfusion are more prone to CMV activation, which in turn led to increased mortality and morbidity in terms of increased ICU stay, longer duration of mechanical ventilation, and higher rates of nosocomial infections. However, severe CMV as initial presentation mimicking dengue infection is rare. We recently came across seven cases with positive CMV serology at ICU admission, which we discuss in the light of current literature.

  10. Use of diploid human fibroblasts as a model system to culture, grow, and study human cytomegalovirus infection.

    Science.gov (United States)

    Fortunato, Elizabeth A

    2014-01-01

    Primary human diploid fibroblasts are used routinely to study host/pathogen interactions of human cytomegalovirus (HCMV). Fibroblasts' ease of culture and tremendous permissiveness for infection allow the study of all facets of infection, an abbreviated list of which includes ligand/receptor interactions, activation of cell signaling responses, and dysregulation of the cell cycle and DNA repair processes. Another advantage to fibroblasts' permissiveness for HCMV is the capability to grow high titer stocks of virus in them. This chapter will discuss the production of viral stocks of HCMV in primary human fibroblasts, commencing with culturing and infection of cells and continuing through harvest, titration (determining the infectious capacity of a particular virus preparation), and storage of viral stocks for use in downstream experiments.

  11. Real-time transcriptional profiling of cellular and viral gene expression during lytic cytomegalovirus infection.

    Directory of Open Access Journals (Sweden)

    Lisa Marcinowski

    2012-09-01

    Full Text Available During viral infections cellular gene expression is subject to rapid alterations induced by both viral and antiviral mechanisms. In this study, we applied metabolic labeling of newly transcribed RNA with 4-thiouridine (4sU-tagging to dissect the real-time kinetics of cellular and viral transcriptional activity during lytic murine cytomegalovirus (MCMV infection. Microarray profiling on newly transcribed RNA obtained at different times during the first six hours of MCMV infection revealed discrete functional clusters of cellular genes regulated with distinct kinetics at surprising temporal resolution. Immediately upon virus entry, a cluster of NF-κB- and interferon-regulated genes was induced. Rapid viral counter-regulation of this coincided with a very transient DNA-damage response, followed by a delayed ER-stress response. Rapid counter-regulation of all three clusters indicated the involvement of novel viral regulators targeting these pathways. In addition, down-regulation of two clusters involved in cell-differentiation (rapid repression and cell-cycle (delayed repression was observed. Promoter analysis revealed all five clusters to be associated with distinct transcription factors, of which NF-κB and c-Myc were validated to precisely match the respective transcriptional changes observed in newly transcribed RNA. 4sU-tagging also allowed us to study the real-time kinetics of viral gene expression in the absence of any interfering virion-associated-RNA. Both qRT-PCR and next-generation sequencing demonstrated a sharp peak of viral gene expression during the first two hours of infection including transcription of immediate-early, early and even well characterized late genes. Interestingly, this was subject to rapid gene silencing by 5-6 hours post infection. Despite the rapid increase in viral DNA load during viral DNA replication, transcriptional activity of some viral genes remained remarkably constant until late-stage infection, or was

  12. Activation of PPAR{gamma} by Human Cytomegalovirus for de novo Replication Impairs Migration and Invasiveness of Cytotrophoblast from Early Placenta

    DEFF Research Database (Denmark)

    Rauwel, Benjamin; Mariamé, Bernard; Martin, Hélène;

    2010-01-01

    Human cytomegalovirus (HCMV) contributes to pathogenic processes in immuno-suppressed individuals, in fetuses and in neonates. In the present report by using reporter gene activation assays and confocal microscopy in the presence of specific antagonist we show for the first time that HCMV infection...

  13. Human cytomegalovirus IE2 protein interacts with transcription activating factors

    Institute of Scientific and Technical Information of China (English)

    徐进平; 叶林柏

    2002-01-01

    The human cytomegalovirus (HCMV) IE86 Cdna was cloned into Pgex-2T and fusion protein GST-IE86 was expressed in E. Coli. SDS-PAGE and Western blot assay indicated that fusion protein GST-IE86 with molecular weight of 92 ku is soluble in the supernatant of cell lysate. Protein GST and fusion protein GST-IE86 were purified by affinity chromatography. The technology of co-separation and specific affinity chromatography was used to study the interactions of HCMV IE86 protein with some transcriptional regulatory proteins and transcriptional factors. The results indicated that IE86 interacts separately with transcriptional factor TFIIB and promoter DNA binding transcription trans-activating factors SP1, AP1 and AP2 to form a heterogenous protein complex. These transcriptional trans-activating factors, transcriptional factor and IE86 protein were adsorbed and retained in the affinity chromatography simultaneously. But IE86 protein could not interact with NF-Кb, suggesting that the function of IE86 protein that can interact with transcriptional factor and transcriptional trans-activating factors has no relevance to protein glycosylation. IE86 protein probably has two domains responsible for binding transcriptional trans-activating regulatory proteins and transcriptional factors respectively, thus activating the transcription of many genes. The interactions accelerated the assembly of the transcriptional initiation complexes.

  14. Perforation of the bowel due to cytomegalovirus infection in a man with AIDS: surgery is not always necessary!

    Science.gov (United States)

    Yoganathan, Katie Tharshana; Morgan, Andrew Roger; Yoganathan, Kathir G

    2016-01-01

    Cytomegalovirus (CMV) infection is the most common viral opportunistic infection in immunocompromised patients and is a rare cause of bowel perforation. It invariably requires surgical intervention and is often fatal. We report a 50-year-old Caucasian man with AIDS, presented 3 weeks after developing abdominal pain and distension. He was treated for CMV retinitis in the past. His adherence to antiretroviral therapy was poor. Examination revealed a recurrence of active CMV retinitis. His abdomen was tender and distended. The plain X-ray of the abdomen revealed a double wall sign (Rigler's sign), indicating pneumoperitoneum due to the bowel perforation. The upper endoscopy was normal. His CD4 count was 30 cells/mm(3) He was treated with cidofovir infusion. He made a full recovery, without requiring any form of surgery. However, he died of adult respiratory distress syndrome 14 months later, due to iatrogenic acute pancreatitis. PMID:27440845

  15. Control of human cytomegalovirus gene expression by differential histone modifications during lytic and latent infection of a monocytic cell line.

    Science.gov (United States)

    Ioudinkova, Elena; Arcangeletti, Maria Cristina; Rynditch, Alla; De Conto, Flora; Motta, Federica; Covan, Silvia; Pinardi, Federica; Razin, Sergey V; Chezzi, Carlo

    2006-12-15

    Non-differentiated THP-1 cells can be infected by human cytomegalovirus (HCMV) Towne strain, which persists in these cells in a non-active (latent) form without undergoing a productive cycle. The same cells become permissive for HCMV lytic infection after induction of cell differentiation by treatment with 12-O-tetradecanoylphorbol-13-acetate. We used this cellular model to study the possible role of histone modifications in the control of HCMV latency. Using chromatin immunoprecipitation with antibodies against histone H3 acetylated or dimethylated in position K9, we demonstrated that in lytically infected cells the HCMV enhancer was associated with heavy acetylated but not dimethylated H3. In the case of latent infection, the HCMV enhancer was associated with neither acetylated nor dimethylated H3. HCMV genes encoding DNA polymerase (early), pp65 (early-late) and pp150 (late) proteins were associated preferentially with acetylated H3 in lytically infected cells and with dimethylated H3 in latently infected cells. These data strongly suggest that K9 methylation of H3 is involved in HCMV gene repression, while association of the above genes with acetylated histones is likely to be necessary for active transcription. It can be postulated that the same histone modifications are used to mark active and repressed genes in both cellular and viral chromatin. PMID:16989963

  16. Clinical manifestations of cytomegalovirus-associated posterior uveitis and panuveitis in patients without human immunodeficiency virus infection

    NARCIS (Netherlands)

    K. Pathanapitoon (Kessara); N. Tesavibul (Nattaporn); P. Choopong (Pitipol); S. Boonsopon (Sutasinee); N. Kongyai (Natedao); S. Ausayakhun (Somsanguan); P. Kunavisarut (Paradee); A. Rothova (Aniki)

    2013-01-01

    textabstractImportance: Little attention has been paid to clinical features of cytomegalovirus (CMV) infections in individuals without human immunodeficiency virus (HIV). Objective: To describe the clinical manifestations and comorbidities of patients without HIV infection who have CMV-associated po

  17. Congenital cytomegalovirus infection of the brain: MR imaging and ultrasonographic findings of parventricular cysts

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Woo Mok; Hwang, Mi Soo [College of Medicine, Yeungnam Univ., Daegu (Korea, Republic of)

    2002-07-01

    Although the neuroradiological findings of congenital cytomegalovirus (CMV) infection are well known, little has been reported concerning the imaging findings of paraventricular cysts occurring in patients with cytomegalovirus infection involving the brain. The purpose of this study is to describe the features of paraventricular cysts observed at MRI and ultrasonography. MR and ultrasonographic studies of ten patients with congenital cytomegalovirus infections involving the brain were retrospectively reviewed. Diagnosis was confirmed by positive culture of the virus in urine (n=4), the presence of CMV Ig G antibody (n=4), or positive CMV Ig M antibody (n=2), and on the basis of characteristic MR imaging findings. Initial MRI in all patients and initial ultrasonography in four of five with paraventricular cysts were performed. Three patients underwent follow-up MRI and ultrasonography for the evaluation of cystic change, and the size, location, bilaterality and morphology of the cysts were evaluated. Bilateral paraventricular cysts averaging 15 (range. 10-23) mm in size were found in five of the ten patients (50%). They were adjacent to the foramen of Monro in three cases, the occipital horn in one, an dthe temporal horn in one. MR imaging showed that the fluid content of all cysts was of similar signal intensity to cerebrospinal fluid (T1-WI, hypointense; T2-WI, hyperintense). The ultrasonographic findings varied: there was one pure cyst and one with a thick wall and septations, and two contained complex fluid. In three patients, follow up MRI and ultrasonography showed that the cysts disappeared after 4-23 months. Although paraventricular cysts may appear at MRI to be purely cystic, ultrasonography may indicate that their contents are more complex, or that septations are present.

  18. Congenital cytomegalovirus infection of the brain: MR imaging and ultrasonographic findings of parventricular cysts

    International Nuclear Information System (INIS)

    Although the neuroradiological findings of congenital cytomegalovirus (CMV) infection are well known, little has been reported concerning the imaging findings of paraventricular cysts occurring in patients with cytomegalovirus infection involving the brain. The purpose of this study is to describe the features of paraventricular cysts observed at MRI and ultrasonography. MR and ultrasonographic studies of ten patients with congenital cytomegalovirus infections involving the brain were retrospectively reviewed. Diagnosis was confirmed by positive culture of the virus in urine (n=4), the presence of CMV Ig G antibody (n=4), or positive CMV Ig M antibody (n=2), and on the basis of characteristic MR imaging findings. Initial MRI in all patients and initial ultrasonography in four of five with paraventricular cysts were performed. Three patients underwent follow-up MRI and ultrasonography for the evaluation of cystic change, and the size, location, bilaterality and morphology of the cysts were evaluated. Bilateral paraventricular cysts averaging 15 (range. 10-23) mm in size were found in five of the ten patients (50%). They were adjacent to the foramen of Monro in three cases, the occipital horn in one, an dthe temporal horn in one. MR imaging showed that the fluid content of all cysts was of similar signal intensity to cerebrospinal fluid (T1-WI, hypointense; T2-WI, hyperintense). The ultrasonographic findings varied: there was one pure cyst and one with a thick wall and septations, and two contained complex fluid. In three patients, follow up MRI and ultrasonography showed that the cysts disappeared after 4-23 months. Although paraventricular cysts may appear at MRI to be purely cystic, ultrasonography may indicate that their contents are more complex, or that septations are present

  19. Syphilis, hepatitis A, hepatitis B, and cytomegalovirus infection in homosexual men in Antwerp.

    OpenAIRE

    Coester, C H; Avonts, D; Colaert, J; Desmyter, J; Piot, P.

    1984-01-01

    In a homosexual communication centre in Antwerp 196 homosexual men were screened for seromarkers of syphilis, hepatitis A (HAV), hepatitis B (HBV) and cytomegalovirus (CMV). A comparison group consisted of 118 heterosexual men attending a venereal disease clinic in Antwerp. Treponemal antibodies were found in 7.1% of homosexual men, of whom half gave no history of past or present infection. Anti HAV was present in 43.3%, HBV seromarkers in 34.4%, and CMV antibodies in 71.2% of homosexual men....

  20. THE STRATEGIES FOR PREVENTING AND TREATING INFECTION OF CYTOMEGALOVIRUS IN BONE MARROW TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    In bone marrow transplantation (BMT), cytomegalovirus (CMV) interstitial pneumonitis (IP) is one of the most dangerous complications, which has been the first important cause to lead the failure of BMT. At present, there is no effective and specific therapy for CMV-IP, therefore how to prevent CMV infection effectively is a top task. From 1991 to 1996, we used comprehensive steps to prevent CMV-IP in BMT, and none of 14 patients developed CMV-IP. The preventing results that we achieved by using the steps were quite satisfied.

  1. Magnetic resonance imaging of the brain in congenital rubella virus and cytomegalovirus infections

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, K.; Ando, M.; Makino, M.; Takanashi, J.; Fujimoto, N.; Niimi, H. (Chiba Univ. School of Medicine (Japan). Dept. of Pediatrics)

    1991-06-01

    Two children with congenital rubella virus and six with cytomegalovirus (CMV) infections, were examined by magnetic resonance (MR) and CT. Cranial MR imaging (MRI) with T2-weighted spin-echo (SE) and inversion recovery (IR) sequences demonstrated the following: Periventricular hyperintensity (4), subcortical hyperintensity (5), delayed myelination (4), oligo/pachygyria (2), cerebellar hypoplasia (2). This study showed that the more-disabled children had more marked abnormal MRI findings. MRI was more effective in the detection of parenchymal lesion than was CT, although intraventricular calcification was better visualized with CT. (orig.).

  2. Magnetic resonance imaging of the brain in congenital rubella virus and cytomegalovirus infections

    International Nuclear Information System (INIS)

    Two children with congenital rubella virus and six with cytomegalovirus (CMV) infections, were examined by magnetic resonance (MR) and CT. Cranial MR imaging (MRI) with T2-weighted spin-echo (SE) and inversion recovery (IR) sequences demonstrated the following: Periventricular hyperintensity (4), subcortical hyperintensity (5), delayed myelination (4), oligo/pachygyria (2), cerebellar hypoplasia (2). This study showed that the more-disabled children had more marked abnormal MRI findings. MRI was more effective in the detection of parenchymal lesion than was CT, although intraventricular calcification was better visualized with CT. (orig.)

  3. Effects of macrophages In Resistance to Murine Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    M. Aminzedeh

    1978-06-01

    Full Text Available In a preliminary experiment. the protective effects of ' peritoneal macrophages was shown by transferring macroph. ages fr-om adult mice to newborn and to 7 and 14 days old mice. It suckling mice from intraperitoneal infection with MCMV by reducing the mortality rate from 100% to 27%.was demontrated that such transplentatton protect

  4. Effects of macrophages In Resistance to Murine Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    M. Aminzedeh

    1978-01-01

    Full Text Available In a preliminary experiment. the protective effects of ' peritoneal macrophages was shown by transferring macroph. ages fr-om adult mice to newborn and to 7 and 14 days old mice. It suckling mice from intraperitoneal infection with MCMV by reducing the mortality rate from 100% to 27%.was demontrated that such transplentatton protect

  5. Association of an overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis with cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Toyoda-Akui M

    2011-05-01

    Full Text Available Megumi Toyoda-Akui1,4, Hiroaki Yokomori1, Fumihiko Kaneko1,4, Yuki Shimizu1, Hajime Takeuchi1, Kumiko Tahara1, Hide Yoshida1, Hirobumi Kondo1, Tadashi Motoori2, Makoto Ohbu3, Masaya Oda5, Toshifumi Hibi61Department of Internal Medicine, 2Division of Pathology, Kitasato Medical Center Hospital, Kitasato University, Saitama; 3Department of Pathology, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa; 4Department of Internal Medicine, Saitama Social Insurance Hospital, Saitama; 5Organized Center of Clinical Medicine, International University of Health and Welfare, Tokyo; 6Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, JapanAbstract: A 63-year-old woman, who presented with severe jaundice and elevated serum conjugated bilirubin level, denied alcohol and drug use and showed no evidence of viral hepatitis. Based on clinical and laboratory features, she was diagnosed with autoimmune hepatitis with primary biliary cirrhosis. Hematological and immunochemical assays, radiographic imaging, clinical examination, and liver biopsy were conducted. Laboratory results were the following: negative for fluorescence antinuclear antibody, negative for antismooth muscle antibodies but positive for antinuclear antibody (enzyme-linked immunosorbent assay and antimitochondrial M2 antibody, high titers of serum globulin, and positive for cytomegalovirus IgM. Liver biopsy showed submassive lobular necrosis, inflammation with broad areas of parenchymal collapse, and chronic nonsuppurative destructive cholangitis. The patient responded well to corticosteroid therapy. This case might illustrate an association between cytomegalovirus infection and the occurrence of autoimmune hepatitis.Keywords: autoimmune hepatitis, fluorescence antinuclear antibody, enzyme linked immuno sorbent assay, primary biliary cirrhosis, cytomegalovirus infection

  6. Role of codon usage and tRNA changes in rat cytomegalovirus latency and (re)activation.

    Science.gov (United States)

    Kanduc, Darja

    2016-06-01

    Herpesviruses can remain in their hosts by establishing a latent infection with a low pattern of viral gene expression. Passage from latency to reactivation may occur under particular conditions such as immunosuppressive treatments or during fetal development, and often is accompanied by heavy pathologic sequelae. To investigate the molecular basis underlying herpesvirus latency and (re)activation, codon usage of rat cytomegalovirus was comparatively analyzed with respect to the rat codon usage. Two major points stand out as follows: (i) six codons - GCG (Ala), CCG (Pro), CGG (Arg), CGC (Arg), TCG (Ser), and ACG (Thr) - are rare in rat genes and intensively used in rat cytomegalovirus coding sequences; (ii) in many instances, the codons seldom used by the host are clustered along viral sequences coding for single amino acid repeats such as poly-Ala and poly-Thr stretches. The results indicate that rare host codons and their iteration along viral sequences might represent major constraints that lock rat cytomegalovirus translation in its host during the viral latent phase. Consequently, the data also suggest a link between rat cytomegalovirus quiescence/activation and the functional tRNA coadaptation phenomenon. Indeed, increases in minor tRNA species corresponding to rare rat codons mark rat cell proliferation and might rescue difficult viral translational contexts. Ala isoaccepting-tRNA (CGC) is reported as an example. On the whole, the present findings may contribute to explain how the molecular mechanisms that normally control host gene expression can silence/(re)activate viral gene expression, and might address research toward new approaches in anti-viral therapeutics. PMID:26875974

  7. Relationship between TLR4 signalling alterations and effective human cytomegalovirus infection

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    Germini D.

    2014-09-01

    Full Text Available Toll-like receptors (TLR, the main class of immune-sensor molecules triggering the innate immunity pathways, are known to be involved in the infection of different RNA and DNA viruses, including herpesviruses. Human cytomegalovirus (HCMV is a widespread human beta-herpesvirus that infects 80–90 % of the world’s population and it can cause severe and even fatal diseases in immunocompromised patients and it is also responsible for birth defects as a consequence of congenital infection. Aim of this review is to discuss the existing data regarding the role of TLRs in HCMV concentrating mainly on TLR4. A better understanding in this relationship could be exploited for the development of efficient early diagnosis methodologies and anti viral therapies.

  8. Strategies to control human cytomegalovirus infection in adult hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Lilleri, Daniele; Gerna, Giuseppe

    2016-09-01

    Human cytomegalovirus (HCMV) represents the major viral complication after hematopoietic stem cell transplantation. HCMV infection may be controlled by the reconstituting immune system and remain subclinical or can lead to severe systemic and/or organ disease (mainly pneumonia and gastroenteritis) when immune reconstitution is delayed or impaired. In order to prevent the occurrence of HCMV disease, a prompt diagnosis of HCMV infection is mandatory. The adoption of pre-emptive therapy strategies guided by virological monitoring dramatically reduced the occurrence of HCMV disease. However, late-onset end-organ disease may occur in some patients with apparent immune reconstitution. In the near future, introduction of immunological monitoring and immunotherapies could markedly improve management of HCMV infection. PMID:27485084

  9. Epidemiology of cytomegalovirus infection in pregnant women living in the Greater Romagna Area, Italy

    Directory of Open Access Journals (Sweden)

    Patrizia Billi

    2015-12-01

    Full Text Available Background. Aim of this study was to assess the incidence of Cytomegalovirus (CMV infection in pregnant women living in Romagna area, in North East Italy to implement the best management of this infection. Materials and Methods. In 2012, 23,727 serological tests for CMV IgG and IgM antibodies were performed in the Microbiology Unit, the Hub Laboratory of the Greater Romagna Area: 6931 were pregnant women. Results and Conclusions. 179 subjects were positive for CMV IgM antibodies: 82 were not pregnant; 97 were IgM positive during pregnancy or in the course of a pre-conception evaluation. The detected incidence of the CMV infection in pregnancy (calculated at 1.40% actually validates the literature data. This study’s findings clearly underline the usefulness of testing the CMV specific immune response in the pre-conception period or as early as possible during pregnancy.

  10. Asymptomatic superior mesenteric vein thrombosis as unusual complication of acute cytomegalovirus infection: a case report

    Directory of Open Access Journals (Sweden)

    Michele Bertoni

    2015-10-01

    Full Text Available We describe a 39-year-old male who presented with a fever of unknown origin, the diagnostic work-up of which disclosed an acute cytomegalovirus (CMV infection complicated by a partial superior mesenteric vein (SMV thrombosis. Further investigations revealed the presence of factor V Leiden mutation. Oral anticoagulant treatment with warfarin led to a complete recanalization of SMV two months after. A literature review on the association between CMV infection and portal system (PS thrombosis in immunocompetent patients was performed. We found that, in agreement with our case, in a minority of case reports patients did not complain of abdominal pain, but presented with a mononucleosis-like syndrome with malaise and prolonged fever and displayed a variable elevation of aminotransferase levels. Interestingly, most of them exhibited a limited extension of portal thrombosis. On the whole, these data suggest that PS thrombosis during acute CMV infection may be an underestimated complication.

  11. Early-life environment influencing susceptibility to cytomegalovirus infection

    DEFF Research Database (Denmark)

    Mortensen, Laust Hvas; Maier, A B; Slagbom, P E;

    2012-01-01

    genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs (n=844) and their middle-aged offspring and the offspring's partners (n=1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins...... number for partners was 71% (Penvironment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection......--even under continuous within-partnership exposure--appears to be more strongly influenced by early-life environment than by genetic factors and adult environment....

  12. THE ANALYSIS OF HUMAN CYTOMEGALOVIRUS INFECTION DURING PREGNANCY IN QINBA MOUNTAINOUS AREA

    Institute of Scientific and Technical Information of China (English)

    李芬; 韩蓁; 于学文; 李琦; 李燕琴; 史小薇; 张富昌

    2003-01-01

    Objective To study the epidemiology of cytomegalovirus (CMV) infection in Qinba mountainous area Shaanxi Province China, where there was high prevalence of mental retardation(MR) in children. Methods 367 pregnant women in Qinba mountainous area were monitored with ELISA and PCR and presented with questionnaire. We detected the following: CMV-DNA in urine of 63 neonates born within two weeks whose mother infected CMV during pregnancy and CMV-DNA in breast milk post-delivery within two weeks of 61 women infected and 84 women non-infected. Results Infection rate of CMV in mental retardation prevalent area was 19.62%, the incidence of transmission in uterus was 33.33%, the incidence of excretion by breast milk was 39.34%, CMV infection during pregnancy relates to age, education, economic states, pregnant frequency and pathological delivery. It has no relation with gestational age. Conclusion The study points out that attention should also be paid to detecting CMV infection during pregnancy in mental retardation prevalence. Less education, worse financial condition, more frequent or pathological delivery should be regarded as high risk factors of CMV infection during pregnancy.

  13. Immune-based guidance of foscarnet treatment duration in a transplant recipient with ganciclovir-resistant cytomegalovirus infection.

    Science.gov (United States)

    Mihm, Janine; Leyking, Sarah; Dirks, Jan; Smola, Sigrun; Fliser, Danilo; Sester, Urban; Sester, Martina; Wilkens, Heinrike; Rissland, Jürgen

    2016-09-01

    A lung and kidney transplant recipient underwent cytomegalovirus (CMV) primary infection with a UL97 mutation. Combined monitoring of viral load and CMV-specific CD4 T-cells allowed reduction of treatment duration with foscarnet, and illustrates how knowledge on the individual immunocompetence towards CMV may be used to individualize duration of antiviral treatment. PMID:27389910

  14. Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells

    DEFF Research Database (Denmark)

    Fornara, O; Rahbar, A; Odeberg, J;

    2016-01-01

    Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express...... human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary...... GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co...

  15. Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant.

    Science.gov (United States)

    Revello, Maria Grazia; Gerna, Giuseppe

    2002-10-01

    Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and mental retardation. HCMV infection, while causing asymptomatic infections in most immunocompetent subjects, can be transmitted during pregnancy from the mother with primary (and also recurrent) infection to the fetus. Hence, careful diagnosis of primary infection is required in the pregnant woman based on the most sensitive serologic assays (immunoglobulin M [IgM] and IgG avidity assays) and conventional virologic and molecular procedures for virus detection in blood. Maternal prognostic markers of fetal infection are still under investigation. If primary infection is diagnosed in a timely manner, prenatal diagnosis can be offered, including the search for virus and virus components in fetal blood and amniotic fluid, with fetal prognostic markers of HCMV disease still to be defined. However, the final step for definite diagnosis of congenital HCMV infection is detection of virus in the blood or urine in the first 1 to 2 weeks of life. To date, treatment of congenital infection with antiviral drugs is only palliative both prior to and after birth, whereas the only efficacious preventive measure seems to be the development of a safe and immunogenic vaccine, including recombinant, subunit, DNA, and peptide-based vaccines now under investigation. The following controversial issues are discussed in the light of the most recent advances in the field: the actual perception of the problem; universal serologic screening before pregnancy; the impact of correct counseling on decision making by the couple involved; the role of prenatal diagnosis in ascertaining transmission of virus to the fetus; the impact of preconceptional and periconceptional infections on the prevalence of congenital infection; and the prevalence of congenitally infected babies born to mothers who were immune prior to pregnancy compared to the number born to mothers undergoing primary infection during pregnancy. PMID

  16. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  17. Study of Soluble HLA-G in Congenital Human Cytomegalovirus Infection

    Science.gov (United States)

    Gabrielli, Liliana; Bortolotti, Daria; Gentili, Valentina; Piccirilli, Giulia; Chiereghin, Angela; Pavia, Claudia; Bolzani, Silvia; Guerra, Brunella; Simonazzi, Giuliana; Cervi, Francesca; Capretti, Maria Grazia; Luca, Dario Di; Landini, Maria Paola; Lazzarotto, Tiziana

    2016-01-01

    Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that is expressed during pregnancy contributing to maternal-fetal tolerance. HLA-G can be expressed as membrane-bound and soluble forms. HLA-G expression increases strongly during viral infections such as congenital human cytomegalovirus (HCMV) infections, with functional consequences in immunoregulation. In this work we investigated the expression of soluble (s)HLA-G and beta-2 microglobulin (component of HLA) molecules in correlation with the risk of transmission and severity of congenital HCMV infection. We analyzed 182 blood samples from 130 pregnant women and 52 nonpregnant women and 56 amniotic fluid samples from women experiencing primary HCMV infection. The median levels of sHLA-G in maternal serum of women with primary HCMV infection were higher in comparison with nonprimary and uninfected pregnant women (p < 0.001). AF from HCMV symptomatic fetuses presented higher sHLA-G levels in comparison with infected asymptomatic fetuses (p < 0.001), presence of HLA-G free-heavy chain, and a concentration gradient from amniotic fluid to maternal blood. No significant statistical difference of beta-2 microglobulin median levels was observed between all different groups. Our results suggest the determination of sHLA-G molecules in both maternal blood and amniotic fluid as a promising biomarker of diagnosis of maternal HCMV primary infection and fetal HCMV disease. PMID:27699182

  18. Citomegalovirose congênita: relato de caso Congenital cytomegalovirus infection: a case report

    Directory of Open Access Journals (Sweden)

    Patrícia de Fátima Azevedo

    2005-12-01

    Full Text Available A citomegalovirose congênita sintomática é entidade clínica de grande importância devido a sua vasta sintomatologia fetal. No Brasil, o diagnóstico intra-útero é ainda pouco realizado, apesar do grande arsenal propedêutico. Relatamos um caso de citomegalovirose congênita grave com hepatoesplenomegalia, agenesia parcial do vérmix cerebelar, calcificações intracranianas, placentomegalia, aumento da ecogenicidade intestinal e renal, cardiomegalia, hipoplasia pulmonar, derrame pericárdico e ascite. A ressonância nuclear magnética fetal foi utilizada para confirmação dos achados ultra-sonográficos. A amniocentese foi realizada para análise do líquido amniótico por meio da PCR, sendo evidenciado resultado positivo. O óbito fetal foi constatado na 31ª semana de gestação, sendo confirmados os achados através da citopatologia e estudo anatomopatológico do natimorto. O arsenal propedêutico existente, na atualidade, para diagnóstico intra-útero da citomegalovirose congênita é de grande importância para confirmação diagnóstica e determinação do prognóstico fetal.Congenital cytomegalovirus infection is an important clinical entity, due to its sonographic symptomatology. In Brazil, in utero diagnosis is not accomplished despite the improvements in diagnostic methods. We report a congenital infection including: splenomegaly and hepatomegaly, hypoplasia of the cerebellar vermis, intracranial calcifications, hyperechoic kidneys, hyperechoic bowel, cardiomegaly, lung hypoplasia, ascites, and pericardial effusion. Fetal magnetic resonance imaging confirmed the sonographic findings. Amniocentesis was performed for cytomegalovirus PCR in amniotic fluid, which confirmed fetal infection. Fetal loss occurred in the 31st week of pregnancy. Necropsy studies confirmed the sonographic findings. The diagnostic methods have been useful to confirm congenital cytomegalovirus infection and to establish fetal outcome.

  19. Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA-Recognition Independent Manner.

    Science.gov (United States)

    Proff, Julia; Walterskirchen, Christian; Brey, Charlotte; Geyeregger, Rene; Full, Florian; Ensser, Armin; Lehner, Manfred; Holter, Wolfgang

    2016-01-01

    In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins.

  20. Acute partial Budd-Chiari syndrome and portal vein thrombosis in cytomegalovirus primary infection: a case report

    Directory of Open Access Journals (Sweden)

    Morard Isabelle

    2006-03-01

    Full Text Available Abstract Background Splanchnic vein thrombosis may complicate inherited thrombotic disorders. Acute cytomegalovirus infection is a rare cause of acquired venous thrombosis in the portal or mesenteric territory, but has never been described extending into a main hepatic vein. Case presentation A 36-year-old immunocompetent woman presented with acute primary cytomegalovirus infection in association with extensive thrombosis in the portal and splenic vein. In addition, a fresh thrombus was evident in the right hepatic vein. A thorough evaluation for a hypercoagulable state was negative. The clinical course, biological evolution, radiological and histological findings were consistent with cytomegalovirus hepatitis complicated by a partial acute Budd-Chiari syndrome and portal thrombosis. Therapeutic anticoagulation was associated with a slow clinical improvement and partial vascular recanalization. Conclusion We described in details a new association between cytomegalovirus infection and acute venous thrombosis both in the portal vein and in the right hepatic vein, realizing a partial Budd-Chiari syndrome. One should be aware that this rare thrombotic event may be complicated by partial venous outflow block.

  1. Analysis of risk factors associated to cytomegalovirus infection in dentistry students.

    Directory of Open Access Journals (Sweden)

    Claudia De la Tejera-Hernández

    2015-06-01

    Full Text Available ABSTRACT Objective: The purpose of the study was to analyze the association between cytomegalovirus (CMV infection in dental students with occupational risk factors and a genetic trait (NKG2C gene deletion. Study design: Case-control study. 176 students were included and divided in two groups according to CMV serological results: those with CMV infection (case group and those without prior infection (control group. Demographic, occupational, and the presence of NKG2C gene deletion were compared between both groups. Results: The presence of CMV IgG antibodies was detected in 104 (59.1% students (case group while 72 (40.9% students were CMV negative (control group. The frequency of patient contact, the use of protective barriers, and the number of reported accidents was compared between the study groups; no significant differences were noted. The appropriate use of infection-control measures was observed in the majority of students in both study groups. In the case group the frequency of NKG2C deletion was 9.7% compared to 5.6% in the control group (p=0.33. Conclusion: No association between the presence of CMV infection with occupational and genetic risk factors was found in this population. Dentists should be aware of the CMV prevalence and risks factors associated to this infection, particularly among child-bearing age dentist women.

  2. The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions.

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    Osnat Tirosh

    Full Text Available Viruses are by definition fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt this machinery for their own benefit. Unlike many viruses, human cytomegalovirus (HCMV does suppress the host translation machinery, and the extent to which translation machinery contributes to the overall pattern of viral replication and pathogenesis remains elusive. Here, we combine RNA sequencing and ribosomal profiling analyses to systematically address this question. By simultaneously examining the changes in transcription and translation along HCMV infection, we uncover extensive transcriptional control that dominates the response to infection, but also diverse and dynamic translational regulation for subsets of host genes. We were also able to show that, at late time points in infection, translation of viral mRNAs is higher than that of cellular mRNAs. Lastly, integration of our translation measurements with recent measurements of protein abundance enabled comprehensive identification of dozens of host proteins that are targeted for degradation during HCMV infection. Since targeted degradation indicates a strong biological importance, this approach should be applicable for discovering central host functions during viral infection. Our work provides a framework for studying the contribution of transcription, translation and degradation during infection with any virus.

  3. Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants.

    Science.gov (United States)

    Kaminski, Hannah; Garrigue, Isabelle; Couzi, Lionel; Taton, Benjamin; Bachelet, Thomas; Moreau, Jean-François; Déchanet-Merville, Julie; Thiébaut, Rodolphe; Merville, Pierre

    2016-02-01

    Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV-specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2(neg) γδ T cells in controlling CMV infection. Here, we assessed if Vδ2(neg) γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high-risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R-) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2(neg) γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2(neg) γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2(neg) γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; Ptransplants may predict CMV infection resolution and antiviral drug resistance.

  4. Sustained CD8+ T cell memory inflation after infection with a single-cycle cytomegalovirus.

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    Christopher M Snyder

    2011-10-01

    Full Text Available Cytomegalovirus (CMV is a β-herpesvirus that establishes a lifelong latent or persistent infection. A hallmark of chronic CMV infection is the lifelong persistence of large numbers of virus-specific CD8+ effector/effector memory T cells, a phenomenon called "memory inflation". How the virus continuously stimulates these T cells without being eradicated remains an enigma. The prevailing view is that CMV establishes a low grade "smoldering" infection characterized by tiny bursts of productive infection which are rapidly extinguished, leaving no detectable virus but replenishing the latent pool and leaving the immune system in a highly charged state. However, since abortive reactivation with limited viral gene expression is known to occur commonly, we investigated the necessity for virus reproduction in maintaining the inflationary T cell pool. We inhibited viral replication or spread in vivo using two different mutants of murine CMV (MCMV. First, famcyclovir blocked the replication of MCMV encoding the HSV Thymidine Kinase gene, but had no impact on the CD8+ T cell memory inflation once the infection was established. Second, MCMV that lacks the essential glycoprotein L, and thus is completely unable to spread from cell to cell, also drove memory inflation if the virus was administered systemically. Our data suggest that CMV which cannot spread from the cells it initially infects can repeatedly generate viral antigens to drive memory inflation without suffering eradication of the latent genome pool.

  5. Cytomegalovirus infection is associated with an increase in systolic blood pressure in older individuals

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    Firth, C.; Harrison, R.; Ritchie, S.; Wardlaw, J.; Ferro, C.J.; Starr, J.M.; Deary, I.J.

    2016-01-01

    Background: Cytomegalovirus (CMV) is a chronic infection that is widely distributed in the population. CMV infects a range of tissues, including endothelium, and viral replication is suppressed by the host immune system. Infection is associated with increased risk of mortality from vascular disease in older people, but the mechanisms behind this have not been determined. Aim: We investigated the association between CMV infection and cardiovascular phenotype in a cohort of healthy elderly donors. Design: CMV serostatus and cardiovascular parameters were determined in the Lothian Birth cohort, which comprises 1091 individuals aged 70 years in whom many environmental, biochemical and radiological correlates of vascular function have been determined. Methods: CMV serostatus was determined by enzyme-linked immunosorbant assay and correlated with a range of biochemical and phenotypic measures. Results: Sixty-five percent of participants were CMV seropositive, which indicates chronic infection. The mean sitting systolic blood pressure (SBP) was 149.2 mmHg in CMV seropositive individuals compared with 146.2 mmHg in CMV seronegative subjects (SD 18.7 vs. 19.7; P obesity, diabetes or high salt intake. This is the first evidence to show that a chronic infection may be an important determinant of blood pressure and could have significant implications for the future management of hypertension. PMID:27071749

  6. Incidence of cytomegalovirus infection among the general population and pregnant women in the United States

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    Dollard Sheila C

    2007-07-01

    Full Text Available Abstract Background Cytomegalovirus (CMV is a common opportunistic infection among HIV-infected individuals, a major source of serious complications among organ-transplant recipients, and a leading cause of hearing loss, vision loss, and mental retardation among congenitally infected children. Women infected for the first time during pregnancy are especially likely to transmit CMV to their fetuses. More children suffer serious disabilities caused by congenital CMV than by several better-known childhood maladies such as Down syndrome or fetal alcohol syndrome Methods Using CMV seroprevalence data from the nationally representative Third National Health and Nutrition Examination Survey, we estimated CMV incidence among the general United States population and among pregnant women. We employed catalytic models that used age-specific CMV seroprevalences as cumulative markers of past infections in order to derive estimates of three basic parameters: the force of infection, the basic reproductive rate, and the average age of infection. Our main focus was the force of infection, an instantaneous per capita rate of acquisition of infection that approximates the incidence of infection in the seronegative population. Results Among the United States population ages 12–49 the force of infection was 1.6 infections per 100 susceptible persons per year (95% confidence interval: 1.2, 2.4. The associated basic reproductive rate of 1.7 indicates that, on average, an infected person transmits CMV to nearly two susceptible people. The average age of CMV infection was 28.6 years. Force of infection was significantly higher among non-Hispanic Blacks (5.7 and Mexican Americans (5.1 than among non-Hispanic Whites (1.4. Force of infection was significantly higher in the low household income group (3.5 than in the middle (2.1 and upper (1.5 household income groups. Based on these CMV incidence estimates, approximately 27,000 new CMV infections occur among seronegative

  7. Quantification of CD8+CD38+ T lymphocytes by flow cytometry does not represent a good biomarker to monitor the reactivation of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation

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    Vânia Abadia Soares Lino

    2011-01-01

    Full Text Available BACKGROUND: Infection/reactivation of cytomegalovirus is a major cause of morbidity and mortality in immunocompromised transplant patients. It has already been observed in kidney and liver transplantation patients that cytomegalovirus disease is accompanied by significant increases in circulating CD8+CD38+ T lymphocytes. There are no reports that study CD8+CD38+ T lymphocytes to monitor/diagnose cytomegalovirus disease in hematopoietic stem cell transplantation patients. OBJECTIVE: The aim of this study was to evaluate some cellular activation markers on circulating mononuclear cells (CD38 and HLA-DR in patients submitted to hematopoietic stem cell transplantation and to establish any correlation with cytomegalovirus disease as diagnosed by antigenemia. METHODS: Blood samples of 15 transplant patients were analyzed by flow cytometry using anti-CD3, anti-CD4, anti-CD8, anti-CD38, CD16, CD56 and anti-HLA-DR monoclonal antibodies and the results were evaluated in respect to cytomegalovirus antigenemia measured by indirect immunofluorescence. Minitab for Windows was used for statistical analysis and a p-value < 0.05 was considered significant. RESULTS: Patients with positive antigenemia did not show any significant increase in the percentages of cells expressing the CD38 or HLADR activation markers when compared to patients with negative antigenemia. On the contrary, all patients showed high percentages of these cells independent of the presence of cytomegalovirus disease. CONCLUSIONS: This study suggests that the investigation of these lymphocyte sub-populations in patients submitted to hematopoietic stem cell transplantation does not seem to contribute to the early identification of cytomegalovirus disease.

  8. Knowledge and practices of obstetricians and gynecologists regarding cytomegalovirus infection during pregnancy--United States, 2007.

    Science.gov (United States)

    2008-01-25

    In the United States, congenital cytomegalovirus (CMV) infection occurs in approximately 1 in 150 live births, leading to permanent disabilities (e.g., hearing loss, vision loss, and cognitive impairment) in approximately 1 in 750 live-born children. A common mode of CMV transmission to a pregnant woman is through close contact with infected bodily fluids such as urine or saliva, especially from young children. Because no vaccine is available and treatment options are limited, renewed attention has been given to prevention of CMV infections among pregnant women through traditional infection-control practices, such as good hand hygiene. These practices have been encouraged by organizations such as CDC and the American College of Obstetricians and Gynecologists (ACOG), which recommend that obstetricians and gynecologists (OB/GYNs) counsel women on careful handling of potentially CMV-infected articles, such as diapers, and thorough hand washing after close contact with young children. Despite this increased emphasis on avoiding infection during pregnancy, few women are aware of CMV infection and how it can be prevented. During March-May 2007, ACOG surveyed a national sample of OB/GYNs to assess their knowledge and practices regarding CMV infection prevention. This report describes the results of that survey, which indicated that fewer than half (44%) of OB/GYNs surveyed reported counseling their patients about preventing CMV infection. These results emphasize the need for additional training of OB/GYNs regarding CMV infection prevention and for a better understanding of the reasons that physician knowledge regarding CMV transmission might not result in patient counseling. PMID:18219267

  9. Human cytomegalovirus gene expression in long-term infected glioma stem cells.

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    Estefania Fiallos

    Full Text Available The most common adult primary brain tumor, glioblastoma (GBM, is characterized by fifteen months median patient survival and has no clear etiology. We and others have identified the presence of human cytomegalovirus (HCMV gene products endogenously expressed in GBM tissue and primary cells, with a subset of viral genes being consistently expressed in most samples. Among these viral genes, several have important oncomodulatory properties, regulating tumor stemness, proliferation, immune evasion, invasion and angiogenesis. These findings lead us to hypothesize that a specific HCMV gene signature may be associated with GBM pathogenesis. To investigate this hypothesis, we used glioma cell lines and primary glioma stem-like cells (GSC infected with clinical and laboratory HCMV strains and measured relative viral gene expression levels along several time points up to 15 weeks post-infection. While HCMV gene expression was detected in several infected glioma lines through week 5 post-infection, only HCMV-infected GSC expressed viral gene products 15 weeks post-infection. Efficiency of infection across time was higher in GSC compared to cell lines. Importantly, HCMV-infected GSC outlived their uninfected counterparts, and this extended survival was paralleled by increased tumorsphere frequency and upregulation of stemness regulators, such as SOX2, p-STAT3, and BMX (a novel HCMV target identified in this study. Interleukin 6 (IL-6 treatment significantly upregulated HCMV gene expression in long-term infected glioma cultures, suggesting that pro-inflammatory signaling in the tumor milieu may further augment HCMV gene expression and subsequent tumor progression driven by viral-induced cellular signaling. Together, our data support a critical role for long-term, low-level HCMV infection in promoting survival, stemness, and proliferation of GSC that could significantly contribute to GBM pathogenesis.

  10. Detection of CMV DNA in the perilymph of a 6-year-old boy with congenital cytomegalovirus infection.

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    Foulon, Ina; Soetens, Oriane; Vleurinck, Leen; Gordts, Frans; Leus, Astrid; Naessens, Anne

    2016-06-01

    We present the case of a 6-year-old boy who received a cochlear implant for profound sensorineural hearing loss after being born with cytomegalovirus (CMV) infection. Even after 6 years, CMV DNA was still found in the perilymph of the cochlea. Our case shows that CMV DNA can be present in the cochlea years after congenital CMV infection, and it can explain why progressive and/or late-onset hearing loss occurs in these children. PMID:27304443

  11. Cytomegalovirus Infection and the Risk of Mortality and Frailty in Older Women: A Prospective Observational Cohort Study

    OpenAIRE

    Wang, George C.; Kao, Wen Hong L.; Murakami, Peter; Xue, Qian-Li; Chiou, Roger B.; Detrick, Barbara; McDyer, John F.; Richard D Semba; Casolaro, Vincenzo; Walston, Jeremy D.; Fried, Linda P.

    2010-01-01

    Cytomegalovirus (CMV), a prevalent pathogen, causes severe disease in immunocompromised humans. However, present understanding is limited regarding the long-term clinical effect of persistent CMV infection in immunocompetent adults. The authors conducted a prospective observational cohort study (1992–2002) of 635 community-dwelling women in Baltimore, Maryland, aged 70–79 years in the Women's Health and Aging Studies to examine the effect of CMV infection on the risk of frailty, a common geri...

  12. RELATIONSHIP BETWEEN CYTOMEGALOVIRUS INFECTION AND THE PRODUCTION OF AN TICARDIOLIPIN ANTIBODY IN RENAL TRANSPLANT RECIPIENTS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the relationship bet wee n cytomegalovirus (CMV) infection and the production of anticardiolipin antibody (ACA) in renal transplant recipients.Methods Polymerase c hain reaction (PCR) was used qualitat ively for detection of CMV-DNA in 146 renal transplant recipients.Meanwhile,enz yme-linked immunosorbent assay (ELISA) was used for detection of ACA-IgG in bl ood serum samples from these recipients and 32 healthy individuals. Results The ACA positive rate was 17.1% among the 146 ren al transplant recipients,and that of the control group was 6.3%.There was no sig nificant difference.However,the ACA positive rate of the renal transplant recipi ents infected with CMV was 31.2%.It was clearly higher than that of those with n o infection of CMV and that of the control group (P<0.005). Con clusion The production of ACA was closely related to CMV infection.It m ight be one of the factors of chronic angiopathy of the transpl anted kidney due to CMV infection.

  13. Pathological spectrum of cytomegalovirus infection of renal allograft recipients-an autopsy study from north India.

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    Joshi, Kusum; Nada, Ritambhra; Radotra, Bishan Das; Jha, Vivekanand; Sakhuja, Vinay

    2004-07-01

    This is a retrospective study of autopsy material to highlight the histo-morphological changes in cytomegalovirus (CMV) infection amongst renal allograft recipients. Nineteen out of 80 patients (23.75%) autopsied during a seventeen-year period (1985-2001) had CMV infection. Pulmonary infection was present in 14 out of 19 cases of which four had isolated lung involvement. Likewise, there were two cases each of isolated oesophageal and renal involvement; one case with isolated colonic involvement. The other 10 cases had multi-organ involvement and the organs involved were kidneys (4), esophagus (6), stomach (1), colon (5), adrenals (3), pancreas (3), liver (1) and spleen (1). Pulmonary infection with CMV was associated with acute pneumonitis in 3 cases and lymphocytic interstitial pneumonitis in 9 instances. Four out of 6 cases had acute tubulo-interstitial nephritis induced by CMV and only two cases had no significant inflammatory response. Glomerular involvement in the form of CMV inclusions in the glomeruli was present in only one case. Gastrointestinal CMV infection (15) presented as acute necrotizing ulceration because of predominant endothelial involvement. Post transplant survival period varied from one month to three years, with majority (14) of the patients having survived for less than one year.

  14. Host genetics and susceptibility to congenital and childhood cytomegalovirus infection: a systematic review

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    Gelemanović, Andrea; Dobberpuhl, Katie; Krakar, Goran; Patarčić, Inga; Kolčić, Ivana; Polašek, Ozren

    2016-01-01

    Aim To summarize available evidence on the role of host genetics in the susceptibility to congenital and childhood cytomegalovirus (CMV) infections by conducting a systematic review of published studies. Methods We searched online databases (PubMed, Web of Science, Scopus and HuGe Navigator) for relevant studies with well-defined inclusion and exclusion criteria and assessed the risk of bias using novel Confounding-Selection-Information bias score (CSI). Results 5105 studies were initially identified, but only 5 met all the inclusion criteria and were analyzed in detail. Polymorphisms of the toll-like receptors (TLRs) and mannose-binding lectin (MBL) genes were shown to have an impact on the CMV infection in infants. Polymorphisms of the TLR2 (rs3804100, rs1898830), TLR4 (rs4986791), and TLR9 (rs352140) were shown to have a role in congenital CMV infection. Low MBL levels were associated with CMV infection in Chinese individuals, a finding that was not replicated in Caucasians. The overall credibility of evidence was weak. Conclusions Based on currently available very limited amount of evidence, it is uncertain whether congenital and childhood CMV infections are under host genetic control. Additional primary studies are needed with more specific research hypotheses that will enable gradual understanding of specific mechanisms of the CMV pathogenesis. More genetic studies in the future will facilitate better understanding of host susceptibility and likely enable novel preventative and curative measures. PMID:27586547

  15. Debilitating Chronic Diarrhea Caused by Generalized Gastrointestinal Cytomegalovirus Infection in an Immunocompetent Adult

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    Emmanouil Telakis

    2014-01-01

    Full Text Available Gastrointestinal cytomegalovirus (CMV infection is a common opportunistic infection in immunocompromised patients, especially patients with acquired immunodeficiency syndrome and transplant recipients. In contrast, CMV infection of the gastrointestinal tract is rare in immunocompetent individuals. We report a case of severe, protracted, and debilitating diarrhea caused by generalized CMV infection of the gastrointestinal tract in an elderly woman with no apparent immunosuppression. An extensive diagnostic investigation demonstrated CMV-associated disease affecting both the upper and lower gastrointestinal tracts (esophagus, small intestine, and colon. Such extensive simultaneous involvement of the alimentary tract in an immunocompetent patient is rare and presents a diagnostic and therapeutic challenge. The diagnosis was based on a combination of endoscopic, histopathological, serological, and polymerase chain reaction analysis findings and our patient was successfully treated with intravenous ganciclovir. Our case demonstrates that gastrointestinal CMV infection should be considered in the differential diagnosis of severe chronic diarrhea in immunocompetent patients and that antiviral treatment may be justified in this setting.

  16. Cidofovir Activity against Poxvirus Infections

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    Robert Snoeck

    2010-12-01

    Full Text Available Cidofovir [(S-1-(3-hydroxy-2-phosphonylmethoxypropylcytosine, HPMPC] is an acyclic nucleoside analog approved since 1996 for clinical use in the treatment of cytomegalovirus (CMV retinitis in AIDS patients. Cidofovir (CDV has broad-spectrum activity against DNA viruses, including herpes-, adeno-, polyoma-, papilloma- and poxviruses. Among poxviruses, cidofovir has shown in vitro activity against orthopox [vaccinia, variola (smallpox, cowpox, monkeypox, camelpox, ectromelia], molluscipox [molluscum contagiosum] and parapox [orf] viruses. The anti-poxvirus activity of cidofovir in vivo has been shown in different models of infection when the compound was administered either intraperitoneal, intranasal (aerosolized or topically. In humans, cidofovir has been successfully used for the treatment of recalcitrant molluscum contagiosum virus and orf virus in immunocompromised patients. CDV remains a reference compound against poxviruses and holds potential for the therapy and short-term prophylaxis of not only orthopox- but also parapox- and molluscipoxvirus infections.

  17. Optimization of Naked DNA Delivery for Interferon Subtype Immunotherapy in Cytomegalovirus Infection

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    Bartlett Emmalene J.

    2003-01-01

    Full Text Available Type I interferon (IFN gene therapy modulates the immune response leading to inflammatory heart disease following cytomegalovirus (CMV infection in a murine model of post-viral myocarditis. Efficacy of different immunisation protocols for the IFN constructs was influenced by the dose of DNA, subtype choice, combination use, pre-medication, and timing of DNA administration. Optimal efficacy was found with bupivacaine treatment prior to DNA inoculation of 200mg IFN DNA 14 days prior to virus challenge. Maximal antiviral and antimyocarditic effects were achieved with this vaccination schedule. Furthermore, inoculation of synergistic IFN subtypes demonstrated enhanced efficacy when delivered either alone or with CMV gB DNA vaccination in the CMV model. Thus naked DNA delivery of IFN provides an avenue of immunotherapy for regulating herpesvirus-induced diseases.

  18. Human cytomegalovirus gene UL76 induces IL-8 expression through activation of the DNA damage response.

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    Helena Costa

    2013-09-01

    Full Text Available Human cytomegalovirus (HCMV, a β-herpesvirus, has evolved many strategies to subvert both innate and adaptive host immunity in order to ensure its survival and propagation within the host. Induction of IL-8 is particularly important during HCMV infection as neutrophils, primarily attracted by IL-8, play a key role in virus dissemination. Moreover, IL-8 has a positive effect in the replication of HCMV. This work has identified an HCMV gene (UL76, with the relevant property of inducing IL-8 expression at both transcriptional and protein levels. Up-regulation of IL-8 by UL76 results from activation of the NF-kB pathway as inhibition of both IKK-β activity or degradation of Ikβα abolishes the IL-8 induction and, concomitantly, expression of UL76 is associated with the translocation of p65 to the nucleus where it binds to the IL-8 promoter. Furthermore, the UL76-mediated induction of IL-8 requires ATM and is correlated with the phosphorylation of NEMO on serine 85, indicating that UL76 activates NF-kB pathway by the DNA Damage response, similar to the impact of genotoxic drugs. More importantly, a UL76 deletion mutant virus was significantly less efficient in stimulating IL-8 production than the wild type virus. In addition, there was a significant reduction of IL-8 secretion when ATM -/- cells were infected with wild type HCMV, thus, indicating that ATM is also involved in the induction of IL-8 by HCMV. In conclusion, we demonstrate that expression of UL76 gene induces IL-8 expression as a result of the DNA damage response and that both UL76 and ATM have a role in the mechanism of IL-8 induction during HCMV infection. Hence, this work characterizes a new role of the activation of DNA Damage response in the context of host-pathogen interactions.

  19. Effects of oral valganciclovir prophylaxis for cytomegalovirus infection in heart transplant patients

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    Doesch AO

    2012-10-01

    Full Text Available Andreas O Doesch,1 Janika Repp,1 Nina Hofmann,1 Christian Erbel,1 Lutz Frankenstein,1 Christian A Gleissner,1 Constanze Schmidt,1 Arjang Ruhparwar,2 Christian Zugck,1 Paul Schnitzler,3 Philipp Ehlermann,1 Thomas J Dengler,4 Hugo A Katus11Department of Cardiology, 2Department of Cardiac Surgery, 3Department of Infectious Disease, Virology, University of Heidelberg, Heidelberg, 4Department of Cardiology, SLK Kliniken Heilbronn, Bad Friedrichshall, GermanyBackground: Cytomegalovirus (CMV infection is a serious complication following heart transplantation. This study (June 2003-January 2010 retrospectively assessed the effects of oral valganciclovir prophylaxis in adult heart transplant recipients during the first year after transplantation.Methods: In patients with normal renal function, 900 mg of oral valganciclovir was administered twice daily for 14 days after heart transplant followed by 900 mg per day for following 6 months. In the event of renal insufficiency, valganciclovir was adjusted according to the manufacturer's recommendations. Antigenemia testing for pp65 antigen and simultaneous polymerase chain reaction (PCR were used to document exposure to CMV. From 2003 to 2010, 146 patients (74.0% men of mean age 50.7 ± 10.3 years at the time of heart transplant were included.Results: A total of 16 patients (11.0% of total, 75.0% male had a positive pp65 and PCR result (ie, CMV infection during the year following heart transplant; three of these patients had discontinued valganciclovir prophylaxis within the first 6 months following transplant because of leukopenia, including one patient developed CMV colitis. Two further patients developed CMV pneumonia during prophylactic valganciclovir therapy. Eight patients had positive pp65 and PCR tests in the 6–12 months after heart transplant following cessation of routine prophylaxis. One of these patients developed CMV pneumonia and another developed CMV colitis and CMV pneumonia. Thirty-seven of

  20. Congenital cytomegalovirus infection in pregnancy: a review of prevalence, clinical features, diagnosis and prevention.

    Science.gov (United States)

    Naing, Zin W; Scott, Gillian M; Shand, Antonia; Hamilton, Stuart T; van Zuylen, Wendy J; Basha, James; Hall, Beverly; Craig, Maria E; Rawlinson, William D

    2016-02-01

    Human cytomegalovirus (CMV) is under-recognised, despite being the leading infectious cause of congenital malformation, affecting ~0.3% of Australian live births. Approximately 11% of infants born with congenital CMV infection are symptomatic, resulting in clinical manifestations, including jaundice, hepatosplenomegaly, petechiae, microcephaly, intrauterine growth restriction and death. Congenital CMV infection may cause severe long-term sequelae, including progressive sensorineural hearing loss and developmental delay in 40-58% of symptomatic neonates, and ~14% of initially asymptomatic infected neonates. Up to 50% of maternal CMV infections have nonspecific clinical manifestations, and most remain undetected unless specific serological testing is undertaken. The combination of serology tests for CMV-specific IgM, IgG and IgG avidity provide improved distinction between primary and secondary maternal infections. In pregnancies with confirmed primary maternal CMV infection, amniocentesis with CMV-PCR performed on amniotic fluid, undertaken after 21-22 weeks gestation, may determine whether maternofetal virus transmission has occurred. Ultrasound and, to a lesser extent, magnetic resonance imaging are valuable tools to assess fetal structural and growth abnormalities, although the absence of fetal abnormalities does not exclude fetal damage. Diagnosis of congenital CMV infection at birth or in the first 3 weeks of an infant's life is crucial, as this should prompt interventions for prevention of delayed-onset hearing loss and neurodevelopmental delay in affected infants. Prevention strategies should also target mothers because increased awareness and hygiene measures may reduce maternal infection. Recognition of the importance of CMV in pregnancy and in neonates is increasingly needed, particularly as therapeutic and preventive interventions expand for this serious problem. PMID:26391432

  1. Ganciclovir-Resistant Cytomegalovirus Infection in a Kidney Transplant Recipient Successfully Treated with Foscarnet and Everolimus

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    Viola Menghi

    2016-01-01

    Full Text Available Cytomegalovirus (CMV infection remains a major cause of morbidity, graft failure, and death in kidney transplant recipients. We describe a case of a 53-year-old CMV-seronegative man who underwent renal transplant from a CMV-positive donor and who developed ganciclovir- (GCV- resistant CMV infection. Foscarnet was started while immunosuppressive therapy was modified with the introduction of everolimus minimizing tacrolimus dosage. Only two weeks after the start of this treatment regimen was the patient’s viral load negative. At two-year follow-up the patient has no clinical or laboratory signs of CMV infection and a good and stable renal function or graft survival. In our case, administration of an mTOR inhibitor combined with foscarnet led to rapid and persistent viral clearance without compromising short- and medium-term graft function. This combination therapy supports the need for the kidney transplant community to individualize a target therapy for each type of GCV-resistant CMV infection.

  2. Cyclic cidofovir (cHPMPC prevents congenital cytomegalovirus infection in a guinea pig model

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    McGregor Alistair

    2006-03-01

    Full Text Available Abstract Background Congenital cytomegalovirus (CMV infection is a major public health problem. Antiviral therapies administered during pregnancy might prevent vertical CMV transmission and disease in newborns, but these agents have not been evaluated in clinical trials. The guinea pig model of congenital CMV infection was therefore used to test the hypothesis that antiviral therapy, using the agent agent cyclic cidofovir (cHPMPC, could prevent congenital CMV infection. Results Pregnant outbred Hartley guinea pigs were challenged in the early-third trimester with guinea pig CMV (GPCMV and treated with placebo, or the antiviral agent, cyclic cidofovir. To optimize detection of vertical infection, an enhanced green fluorescent protein (eGFP-tagged virus was employed. Compared to placebo, cyclic cidofovir-treated dams and pups had reduced mortality following GPCMV challenge. The magnitude of GPCMV-induced maternal and fetal mortality in this study was reduced from 5/25 animals in the placebo group to 0/21 animals in the treatment group (p = 0.05, Fisher's exact test. By viral culture assay, antiviral therapy was found to completely prevent GPCMV transmission to the fetus. In control pups, 5/19 (26% were culture-positive for GPCMV, compared to 0/16 of pups in the cyclic cidofovir treatment group (p Conclusion Antiviral therapy with cyclic cidofovir improves pregnancy outcomes in guinea pigs, and eliminates congenital CMV infection, following viral challenge in the third trimester. This study also demonstrated that an eGFP-tagged recombinant virus, with the reporter gene inserted into a dispensable region of the viral genome, retained virulence, including the potential for congenital transmission, facilitating tissue culture-based detection of congenital infection. These observations provide support for clinical trials of antivirals for reduction of congenital CMV infection.

  3. Treatment of Cytomegalovirus Infection with Cidofovir and CMV Immune Globulin in a Lung Transplant Recipient

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    Heinrike Wilkens

    2016-01-01

    Full Text Available Cytomegalovirus (CMV infection after lung transplantation is associated with increased risk for pneumonitis and bronchiolitis obliterans as well as allograft rejection and opportunistic infections. Ganciclovir is the mainstay of prophylaxis and treatment but CMV infections can be unresponsive. Apart from direct antiviral drugs, CMV immunoglobulin (CMVIG preparations may be considered but are only licensed for prophylaxis. A CMV-seronegative 42-year-old man with cystic fibrosis received a lung from a CMV-seropositive donor. Intravenous ganciclovir prophylaxis was delayed until day 12 due to acute postoperative renal failure and was accompanied by five doses of CMVIG (10 g. By day 16, CMV-DNA was detectable and rising; CMV-specific T-cells were undetectable. Switch from ganciclovir to foscarnet prompted a transient decrease in CMV viral load, but after increasing again to reach 3600 copies/mL foscarnet was changed to intravenous cidofovir and CMVIG was restarted. CMV load continued to fluctuate and declined slowly, whereas CMV-specific T-cells were detected five months later and increased thereafter. At last follow-up, the patient was in very good clinical condition with no evidence of bronchiolitis obliterans. No side effects of this treatment were observed. In this hard-to-treat case, the combination of cidofovir with off-label use of CMVIG contributed to a successful outcome.

  4. Congenital cytomegalovirus infection in fraternal twins: a longitudinal case study examining neurocognitive and neurobehavioral correlates.

    Science.gov (United States)

    Llorente, Antolin M; Castillo, Christine L

    2012-01-01

    Cytomegalovirus (CMV) is the most ubiquitous member of the herpes virus family and is the leading cause of congenital (vertical) infection in newborns (Fowler, Stagno, & Pass, 2003; Llorente, Steigmeyer, Cooper, Rivers, & Gazley, 2011; Noyola et al., 2000; Steigmeyer & Llorente, 2010). CMV is related to the group of viruses capable of causing more pernicious infectious diseases, such as chicken pox (Santos de Barona, 1998). Although the virus generally remains dormant, individuals whose symptoms are clinically apparent often are dramatically affected. Common symptomatic characteristics of the virus include microcephaly, jaundice, liver-spleen infections, pneumonia, cardiac anomalies, chorioretinitis, vision loss, sensory-neural hearing loss, mental retardation, and mononucleosis (Demmler, 1991; Kashden, Frison, Fowler, Pass, & Boll, 1998; Noyola et al., 2000; Pass, 2005; Santos de Barona). The prognosis of individuals with CMV is highly variable, and the prognosis of individuals with congenital CMV can usually be determined based on the extent of infection at birth. The purpose of this investigation is to present longitudinal results of neuropsychological evaluation of two dizygotic twin sets (one twin of each set is asymptomatic CMV-positive and the other is uninfected) who were reared in the same environment. In addition, the present findings are discussed within the context of emerging murine and other animal analogues of CMV as well as within the extant CMV literature. PMID:23428280

  5. Impact of Persistent Cytomegalovirus Infection on Dynamic Changes in Human Immune System Profile.

    Directory of Open Access Journals (Sweden)

    Rosanna Vescovini

    Full Text Available Human cytomegalovirus (HCMV imprints the immune system after primary infection, however its effect during chronic infection still needs to be deciphered. In this study we report the variation of blood cell count along with anti-HCMV IgG and T cell responses to pp-65 and IE-1 antigens, that occurred after an interval of five years in a cohort of 25 seropositive healthy adults. We found increased anti-viral IgG antibody responses and intracellular interferon-gamma secreting CD8+ T cell responses to pp-65: a result consistent with memory inflation. With the only exception of shortage in naive CD8+ T cells most memory T cell subsets as well as total CD8+ T cells, T cells, lymphocytes, monocytes and leukocytes had increased. By contrast, none of the cell types tested were found to have increased in 14 subjects stably seronegative. Rather, in addition to a shortage in naive CD8+ T cells, also memory T cell subsets and most other cell types decreased, either in a statistically significant or non-significant manner. The trend of T cell pool representation with regard to CD4/CD8 ratio was in the opposing directions depending on HCMV serology. Globally, this study demonstrates different dynamic changes of most blood cell types depending on presence or absence of HCMV infection. Therefore, HCMV plays a continual role in modulating homeostasis of blood T cells and a broader expanding effect on other cell populations of lymphoid and myeloid origin.

  6. Hepatitis C viremia is associated with cytomegalovirus IgG antibody levels in HIV-infected women.

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    Mark H Kuniholm

    Full Text Available BACKGROUND: Individuals with HIV infection exhibit high cytomegalovirus (CMV IgG levels, but there are few data regarding the association of hepatitis C virus (HCV with the immune response against CMV. METHODS: Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART prior to or at CMV testing. RESULTS: In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 - 4.83; P = 0.004. The association of HCV RNA with CMV IgG differed by age (P(interaction = 0.0007, with a strong association observed among women in the low and middle age tertiles (≤ 45.3 years of age; β = 6.21, 95% CI:3.30 - 9.11, P<0.0001 but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV IgG levels did not affect the association between HCV and CMV. CONCLUSIONS: CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients.

  7. Non-hematopoietic cells in lymph nodes drive memory CD8 T cell inflation during murine cytomegalovirus infection.

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    Nicole Torti

    2011-10-01

    Full Text Available During human and murine cytomegalovirus (MCMV infection an exceptionally large virus-specific CD8 T cell pool is maintained in the periphery lifelong. This anomalous response is only seen for specific subsets of MCMV-specific CD8 T cells which are referred to as 'inflationary T cells'. How memory CD8 T cell inflation is induced and maintained is unclear, though their activated phenotype strongly suggests an involvement of persistent antigen encounter during MCMV latency. To dissect the cellular and molecular requirements for memory CD8 T cell inflation, we have generated a transgenic mouse expressing an MHC class I-restricted T cell receptor specific for an immunodominant inflationary epitope of MCMV. Through a series of adoptive transfer experiments we found that memory inflation was completely dependent on antigen presentation by non-hematopoietic cells, which are also the predominant site of MCMV latency. In particular, non-hematopoietic cells selectively induced robust proliferation of inflationary CD8 T cells in lymph nodes, where a majority of the inflationary CD8 T cells exhibit a central-memory phenotype, but not in peripheral tissues, where terminally differentiated inflationary T cells accumulate. These results indicate that continuous restimulation of central memory CD8 T cells in the lymph nodes by infected non-hematopoietic cells ensures the maintenance of a functional effector CD8 T pool in the periphery, providing protection against viral reactivation events.

  8. Diagnostic value of amplification of human cytomegalovirus DNA from gastrointestinal biopsies from human immunodeficiency virus-infected patients.

    OpenAIRE

    Cotte, L.; Drouet, E.; Bissuel, F.; Denoyel, G A; Trepo, C

    1993-01-01

    In order to assess the value of human cytomegalovirus (HCMV) DNA amplification of gastrointestinal biopsies, we studied 57 human immunodeficiency virus-infected patients with and without gastrointestinal HCMV diseases. After DNA extraction, a 406-bp fragment from the unique short region of the HCMV genome was amplified by 35 cycles of polymerase chain reaction (PCR) and semiquantified from 80 to 80,000 HCMV genomic copies. Among 12 non-AIDS patients, the PCR assay was negative for 11 of 12 du...

  9. Maternal Antibodies Enhance or Prevent Cytomegalovirus Infection in the Placenta by Neonatal Fc Receptor-Mediated Transcytosis

    OpenAIRE

    Maidji, Ekaterina; McDonagh, Susan; Genbacev, Olga; Tabata, Takako; Pereira, Lenore

    2006-01-01

    How human cytomegalovirus (CMV) reaches the fetus across the placenta is unknown. The major viral cause of congenital disease, CMV infects the uterine-placental interface with varied outcomes depending on the strength of maternal humoral immunity and gestational age. Covering the surface of villi that float in blood, syncytiotrophoblasts express the neonatal Fc receptor (FcRn) that transports IgG for passive immunity. Immunohistochemical analysis of early-gestation biopsy specimens showed an ...

  10. A faster immunofluorescence assay for tracking infection progress of human cytomegalovirus

    Institute of Scientific and Technical Information of China (English)

    Yingliang Duan; Lingfeng Miao; Hanqing Ye; Cuiqing Yang; Bishi Fu; Philip H.Schwartz; Simon Rayner; Elizabeth A.Fortunato; Min-Hua Luo

    2012-01-01

    Immunofluorescence assay (IFA) is one of the most frequently used methods in the biological sciences and clinic diagnosis,but it is expensive and time-consuming.To overcome these limitations,we developed a faster and more cost-effective IFA (f-IFA) by modifying the standard IFA,and applied this method to track the progression of human cytomegalovirus (HCMV) infection in different cells.The f-IFA that we developed not only saves time,but also dramatically reduces the quantity of antibody (Ab),which will facilitate the application of IFA in clinic diagnosis,f-IFA requires only 15 min for blocking,10 min incubation for each primary and secondary Abs,followed by 1 min extensive wash after each incubation.Only 25 μl of diluted Ab solution was needed for each coverslip at the primary and secondary Ab incubation steps.In addition,all steps were performed at room temperature.This f-IFA has been applied successfully to follow virion entry (pp65) and expression of viral genes (IE1,UL44,and pp65) in order to track the details of HCMV infection process.We found that ~0.5% HCMV-infected T98G cells formed multiple-micronuclei (IE1 and nucleus staining) and had virus shedding (pp65 staining) by f-IFA,which could not be detected by the traditional IFA.Our results indicated that f-IFA is a sensitive,convenient,fast,and cost-effective method for investigating the details of virus infection progress,especially HCMV infection.The faster and cost-effective feature with higher sensitivity and specilieity implies that f-IFA has potential applications in clinical diagnosis.

  11. Identification of Symptomatic Fetuses Infected with Cytomegalovirus Using Amniotic Fluid Peptide Biomarkers

    Science.gov (United States)

    Leruez-Ville, Marianne; Ramirez-Torres, Adela; Lacroix, Chrystelle; Breuil, Benjamin; Froment, Carine; Bascands, Jean-Loup; Schanstra, Joost P.; Ville, Yves

    2016-01-01

    Cytomegalovirus (CMV) is the most common cause of congenital infection, and is a major cause of sensorineural hearing loss and neurological disabilities. Evaluating the risk for a CMV infected fetus to develop severe clinical symptoms after birth is crucial to provide appropriate guidance to pregnant women who might have to consider termination of pregnancy or experimental prenatal medical therapies. However, establishing the prognosis before birth remains a challenge. This evaluation is currently based upon fetal imaging and fetal biological parameters, but the positive and negative predictive values of these parameters are not optimal, leaving room for the development of new prognostic factors. Here, we compared the amniotic fluid peptidome between asymptomatic fetuses who were born as asymptomatic neonates and symptomatic fetuses who were either terminated in view of severe cerebral lesions or born as severely symptomatic neonates. This comparison allowed us to identify a 34-peptide classifier in a discovery cohort of 13 symptomatic and 13 asymptomatic neonates. This classifier further yielded 89% sensitivity, 75% specificity and an area under the curve of 0.90 to segregate 9 severely symptomatic from 12 asymptomatic neonates in a validation cohort, showing an overall better performance than that of classical fetal laboratory parameters. Pathway analysis of the 34 peptides underlined the role of viral entry in fetuses with severe brain disease as well as the potential importance of both beta-2-microglobulin and adiponectin to protect the injured fetal brain infected with CMV. The results also suggested the mechanistic implication of the T calcium channel alpha-1G (CACNA1G) protein in the development of seizures in severely CMV infected children. These results open a new field for potential therapeutic options. In conclusion, this study demonstrates that amniotic fluid peptidome analysis can effectively predict the severity of congenital CMV infection. This

  12. Identification of Symptomatic Fetuses Infected with Cytomegalovirus Using Amniotic Fluid Peptide Biomarkers.

    Directory of Open Access Journals (Sweden)

    Cyrille Desveaux

    2016-01-01

    Full Text Available Cytomegalovirus (CMV is the most common cause of congenital infection, and is a major cause of sensorineural hearing loss and neurological disabilities. Evaluating the risk for a CMV infected fetus to develop severe clinical symptoms after birth is crucial to provide appropriate guidance to pregnant women who might have to consider termination of pregnancy or experimental prenatal medical therapies. However, establishing the prognosis before birth remains a challenge. This evaluation is currently based upon fetal imaging and fetal biological parameters, but the positive and negative predictive values of these parameters are not optimal, leaving room for the development of new prognostic factors. Here, we compared the amniotic fluid peptidome between asymptomatic fetuses who were born as asymptomatic neonates and symptomatic fetuses who were either terminated in view of severe cerebral lesions or born as severely symptomatic neonates. This comparison allowed us to identify a 34-peptide classifier in a discovery cohort of 13 symptomatic and 13 asymptomatic neonates. This classifier further yielded 89% sensitivity, 75% specificity and an area under the curve of 0.90 to segregate 9 severely symptomatic from 12 asymptomatic neonates in a validation cohort, showing an overall better performance than that of classical fetal laboratory parameters. Pathway analysis of the 34 peptides underlined the role of viral entry in fetuses with severe brain disease as well as the potential importance of both beta-2-microglobulin and adiponectin to protect the injured fetal brain infected with CMV. The results also suggested the mechanistic implication of the T calcium channel alpha-1G (CACNA1G protein in the development of seizures in severely CMV infected children. These results open a new field for potential therapeutic options. In conclusion, this study demonstrates that amniotic fluid peptidome analysis can effectively predict the severity of congenital CMV

  13. Human cytomegalovirus infection inhibits CXCL12- mediated migration and invasion of human extravillous cytotrophoblasts

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    Warner Jessica A

    2012-11-01

    Full Text Available Abstract Background During the first trimester of pregnancy, a series of tightly regulated interactions govern the formation of a highly invasive population of fetal-derived extravillous cytotrophoblasts (EVT. Successful pregnancy is dependent on efficient invasion of the uterine wall and maternal spiral arteries by EVT. Dysregulated trophoblast invasion is associated with intrauterine growth restriction, birth defects, spontaneous abortion and preeclampsia. A number of soluble growth factors, cytokines, and chemokines modulate this process, fine-tuning the temporal and spatial aspects of cytotrophoblast invasion. In particular, the CXCL12/CXCR4 axis has been shown to specifically modulate cytotrophoblast differentiation, invasion, and survival throughout early pregnancy. Infection with human cytomegalovirus (HCMV has been associated with impaired differentiation of cytotrophoblasts down the invasive pathway, specifically dysregulating the response to mitogens including epidermal growth factor (EGF and hepatocyte growth factor (HGF. In this study, the effect of HCMV infection on the CXCL12-mediated migration and invasion of the EVT cell line SGHPL-4 was investigated. Results Infection with HCMV significantly decreased secretion of CXCL12 by SGHPL-4 cells, and induced a striking perinuclear accumulation of the chemokine. HCMV infection significantly increased mRNA and total cell surface expression of the two known receptors for CXCL12: CXCR4 and CXCR7. Functionally, HCMV-infected SGHPL-4 cells were unable to migrate or invade in response to a gradient of soluble CXCL12 in transwell assays. Conclusions Collectively, these studies demonstrate that HCMV impairs EVT migration and invasion induced by CXCL12. As HCMV has the ability to inhibit EVT migration and invasion through dysregulation of other relevant signaling pathways, it is likely that the virus affects multiple signaling pathways to impair placentation and contribute to some of the

  14. RATIONALE FOR A SPECIFIC THERAPY OF CYTOMEGALOVIRUS INFECTION IN CHILDREN WITH BRONCHIAL ASTHMA

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    E. N. Suprun

    2013-01-01

    Full Text Available Abstract. We propose a protocol of treatment in cases of bronchial asthma with cytomegalovirus (CMV persistence. This basic therapy is administered depending on the disease severity, according to the National Programme 2009. The treatment includes administration of human immunoglobulin, with dosage according on CMV antibodies titers. The study has revealed that such regimen of antibody administration based on the content of anti-CMV antibodies in bronchial asthma treatment stops active CMV replication in bronchial mucous membrane, alleviates clinical course of the disease, diminishes changes of immune system typical to children suffering from bronchial asthma and CMV reactivation, thus allowing to reduce the volume of basic therapy, along with maintaining control of asthma control.

  15. Cutaneous cytomegalovirus infection in a child with hyper IgE and specific defects in antibody response to protein vaccines

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    Shahrzad Fallah

    2011-10-01

    Full Text Available Cytomegalovirus (CMV infection is a common opportunistic systemic infection in immunocompromised patients, but skin involvement is rare. Herein, we report a 10 year-old girl from consanguineous parents who was referred to our center because of disseminated maculopapular rash. She had history of upper and lower respiratory tract infections. In immunological studies, increased serum IgE level and decreased responses to tetanus and diphtheria were detected. Polymerase chain reaction (PCR examination of bronchoalveolar lavage and serum sample revealed the presence of CMV. Early diagnosis of cutaneous CMV and appropriate treatment are the key actions in management of patients with underlying immunodeficiencies to avoid further complications.

  16. Cytomegalovirus (For Parents)

    Science.gov (United States)

    ... How it Spreads Diagnosis & Treatment Prevention en español Citomegalovirus About CMV Cytomegalovirus (CMV) is a common infection ... cause significant illness, some kids may develop pneumonia , hepatitis (inflammation of the liver), or a rash. Older ...

  17. Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections

    DEFF Research Database (Denmark)

    Lodding, I P; Sengeløv, Henrik; da Cunha-Bang, C;

    2015-01-01

    of the first CMV infection in the first year post-transplant could be calculated for 193 recipients of haematopoietic stem cell or solid organ transplantation. Factors determining the proportion of recipients with a high diagnostic CMV viral load (≥ 18,200 IU/mL) were explored using mathematical simulation......BACKGROUND: Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2-2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients. METHODS: The CMV doubling time....... FINDINGS: The overall median doubling time was 4.3 days (IQR 2.5-7.8) and was not influenced by prior CMV immunity, or type of transplantation (p > 0.4). Assuming a fixed doubling time of 1.3 days and screening intervals of 7 or 10 days, 11.1% and 33.3% were projected to have a high CMV viral load...

  18. SEROEPIDEMIOLOGY OF TOXOPLASMA, RUBELLA, CYTOMEGALOVIRUS AND HERPES SIMPLEX VIRUS -2 IN WOMEN WITH BAD OBSTETRIC HISTORY. PART II. CYTOMEGALOVIRUS AND HERPES SIMPLEX VIRUS INFECTIONS

    Directory of Open Access Journals (Sweden)

    Abdulghani Mohamed Alsamarai

    2013-10-01

    Full Text Available Bad obstetric history (BOH is reported worldwide and is associated with social and psychological impacts. Cytomegalovirus and herpes simplex virus play an important role in the induction of adverse outcomes of pregnancy. Highest CMV IgG prevalence rate was reported for India (91.05%, while the lowest rate was reported for Iran (14.28%. Unfortunately, six studies in Iraq reported a high prevalence of CMV IgM in non-married, pregnant and women with BOH. The range of recent CMV infection in pregnant women with BOH was from 1.4% in Jordan to 60.2% in Iraq. In women with BOH, the highest HSV 2 prevalence (16.8% was noted in India, while the lowest rate (1.69% was reported in India also. In Arab countries, among women with BOH, HSV 2 IgG and IgM seroprevalence higher rates were reported for Iraq. This literature review highlights the high bacterial and viral maternal infection rate in the developing world. Urgent, concerted action is required to reduce the burden of these infections. In addition to raising awareness about the severity of the problem of maternal infections in the developing world, data from this review will be beneficial in guiding public health policy, research interests and donor funding towards achieving improvement in health care delivery.

  19. Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

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    Felix R Stahl

    Full Text Available Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+ T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.

  20. Seroprevalence and Risk Factors for Cytomegalovirus (CMV) Infections in Adolescent Males

    Science.gov (United States)

    Stadler, Laura Patricia; Bernstein, David I; Callahan, S. Todd; Ferreira, Jennifer; Gorgone Simone, Gina A.; Edwards, Kathryn M.; Stanberry, Lawrence R.; Rosenthal, Susan L.

    2010-01-01

    Background Congenital cytomegalovirus (CMV) is a leading cause of disability, including sensorineural hearing loss, developmental delay, and mental retardation. Although the seroprevalence of CMV and associated exposure and behavioral risk factors have been reported in adolescent females, limited data exists in males. Method Serum was obtained from males (aged 12–17 years) from 6/2006 – 7/2007 in Cincinnati, OH, Galveston, TX, and Nashville, TN and tested for CMV IgG antibody using a commercial assay. Participants completed a computer assisted screening interview to assess seven risk categories. Results A total of 397 adolescent males were screened and 165 (47%) were seropositive. African American race, older age, and exposure to children ≤3 years of age in the home were significant predictors of CMV infection in the univariate analysis. Hispanic ethnicity, group living situations, saliva sharing behaviors, and intimate sexual contact were not associated with CMV infection. However, among those with a history of sexual contact, the number of life time partners was associated with CMV. In the final multivariate model, CMV seroprevalence was significantly higher in African American subjects (OR 1.99 (95% CI [1.27, 2.95]) and subjects >14 years of age (OR 1.1 (95%CI [1.00, 1.28]. With each additional risk factor, males had a 1.6x increased risk of CMV. Conclusions This study indicates that CMV infections are common in adolescent males, increase with age, and are associated with African American race. Further study is needed to understand these risk factors in preparation for a CMV vaccine targeted at both adolescent males and females. Summary This study indicates CMV infections are common in adolescent males, increase with age, and are associated with African Americans. Further study is needed to understand these risk factors in preparation for a CMV vaccine targeted at adolescent males and females. PMID:20936976

  1. Inhibition of p53 transcriptional activity by human cytomegalovirus UL44.

    Science.gov (United States)

    Kwon, Yejin; Kim, Mi-Na; Young Choi, Eun; Heon Kim, Jung; Hwang, Eung-Soo; Cha, Chang-Yong

    2012-05-01

    Human cytomegalovirus (HCMV) stimulates cellular synthesis of DNA and proteins and induces transition of the cell cycle from G(1) to S and G(2) /M phase, in spite of increased amounts of p53 in the infected cells. The immediate early protein IE2-86  kDa (IE86) tethers a transcriptional repression domain to p53; however, its repression of p53 function is not enough to abrogate the G(1) checkpoint function of p53. Other HCMV proteins that suppress the activity of p53 were investigated in this study. Of the HCMV proteins that bind to p53 when assessed by immunoprecipitation and immunoblot analysis, HCMV UL44 was chosen as a candidate protein. It was found that reporter gene containing p53 consensus sequence was activated by transfection with wild type p53, but when plasmids of p53 with IE86 or UL44 were co-transfected, p53 transcriptional activity was decreased to 3-7% of the p53 control in a dose-dependent manner. When the deletion mutant of UL44 was co-transected with p53, the carboxyl one-third portion of UL44 had little effect on inhibition of p53 transcriptional activity. The amount of mRNA p21 was measured in H1299 by real time PCR after transfection of the combination of p53 and UL44 vectors and it was found that p21 transcription by p53 was inhibited dose-dependently by UL44. Increased G0/G1 and decreased S phases in p53 wild type-transfected H1299 cells were recovered to the level of p53 mutant type-transfected ones by the additional transfection of UL44 in a dose-dependent manner. In conclusion, the transcriptional activity of p53 is suppressed by UL44 as well as by IE86. PMID:22376288

  2. Cytomegalovirus infection in autologous stem cell transplant recipients in the era of rituximab.

    Science.gov (United States)

    Jain, Tania; John, Jisha; Kotecha, Aditya; Deol, Abhinav; Saliminia, Tanaz; Revankar, Sanjay; Chandrasekar, Pranatharthi

    2016-08-01

    The incidence of cytomegalovirus (CMV) reactivation/disease after autologous stem cell transplant (ASCT) is much lower than that after allogeneic stem cell transplantation. With the recent use of rituximab during cancer chemotherapy or conditioning regimens prior to transplantation, there has been an increasing concern of opportunistic infections including CMV. In the present study, we reviewed the patients undergoing ASCT from December 2007 to December 2013 to identify those developing CMV reactivation/disease. Out of the 978 patients who underwent ASCT at the Karmanos Cancer Institute, 239 patients were tested for symptomatic CMV reactivation based on clinical suspicion. Of the tested patients, 7/239 (2.9 %) were documented to have CMV reactivation within 90 days of ASCT. The median time to develop CMV viremia was 32 days from transplantation. Of the 239 patients tested, CMV viremia was detected in 3 out of 72 patients who received rituximab as compared to 4 out of 167 patients who did not. Three of these seven viremic patients were treated with anti-viral drugs; viremia resolved in all patients at a median of 24 days. Three patients were found to develop other bacterial and/or fungal infections following CMV viremia. Two of the seven patients died during 1-year follow-up, due to primary disease progression or Candida sepsis. None of the patients developed proven tissue-invasive CMV disease. The study did not evaluate the incidence of asymptomatic CMV infection/reactivation. Despite prior publications based on limited data, rituximab does not appear to contribute to an increased frequency of symptomatic CMV reactivation following ASCT. PMID:27225264

  3. Subacute autonomic and sensory neuropathy closely related to cytomegalovirus infection preceded by frequent syncopal attacks.

    Science.gov (United States)

    Nakao, Koichi; Namekawa, Michito; Kondo, Soichi; Ono, Sayaka; Nakano, Imaharu

    2016-08-31

    A 73-year-old woman who had hypertension developed a slight fever and general malaise with laboratory-proven hepatic dysfunction as well as frequent syncopal attacks 3 months before admission to our hospital. One month later, she developed urinary retention and distal limb numbness. Upon admission, her neurological examination showed reduced limb tendon reflexes, glove and stocking-type numbness, and diminished senses of touch, temperature, pain, and distal leg vibration and position. Serum cytomegalovirus (CMV) IgM antibody and CMV IgG antibody were elevated on admission, and both decreased thereafter, confirming CMV infection. No serum anti-ganglioside antibody was detected. Cerebrospinal fluid revealed a mild pleocytosis and elevated proteins. Compound muscle action potential (CMAP) amplitudes of the tibial and peroneal nerve were slightly reduced. Sensory nerve action potential (SNAP) amplitudes of the median and ulnar nerves were reduced, and sural SNAP was not evoked. Systolic blood pressure dropped 48 mmHg when the patient assumed a standing position from a supine one, demonstrating orthostatic hypotension, and a cold pressor test was abnormal, both indicating an obvious hypofunction of the sympathetic nerve. The postganglionic autonomic nerve appeared to be damaged because the accumulation of [(123)I] meta-iodobenzylguanidine was reduced on myocardial scintigraphy. These findings combined together led us to make a diagnosis of subacute autonomic and sensory neuropathy associated with CMV infection in this case. Following an eventless administration of oral fludrocortisones, intravenous immuno-globulin (IVIg) was given after one month of the hospitalization with a remarkable reduction of the syncope. This case is instructive in two points. One is that there may be a couple of months with syncope alone before the sensory disturbance appearance, and the other is that IVIg may be considerably effective for the patient-annoying syncopes. To our knowledge, this

  4. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines

    Directory of Open Access Journals (Sweden)

    Alex Shimanovsky

    2016-01-01

    Full Text Available Immune thrombocytopenic purpura (ITP is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases the etiology is not known, but viral illness is thought to play a role in the development of some cases of ITP. The current (2011 American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. While most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long term steroid maintenance and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV can persist in spite of standard therapy and that antiviral therapy maybe indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV infected infant and placenta. Furthermore we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV as part of the work-up for severe and refractory ITP prior to splenectomy.

  5. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    Energy Technology Data Exchange (ETDEWEB)

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  6. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    International Nuclear Information System (INIS)

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection

  7. Fever and neutropenia due to cytomegalovirus infection in a breast cancer patient under chemotherapy: a case report

    Directory of Open Access Journals (Sweden)

    Ahmadinejad Z

    2010-06-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Fever in neutropenic patients is a medical emergency which may happen in patients undergoing chemotherapy. The definition of neutropenia varies from institution to institution but is usually defined as an absolute neutrophil count (ANC    < 500 cells/ml or < 1,000 cells/ml with a predicted nadir of < 500 cells/ml. Bacterial and fungal infections are the most important in neutropenic patients. Viral infections with agents such as herpes simplex virus and cytomegalovirus are common but less than other pathogens."n"nCase presentation: We report a patient with fever & neutropenia following cytomegalovirus infection during chemotherapy course for breast cancer."n"nConclusion: Although fever and neutropenia after cytomegalovirus infection is not very common but prompt diagnosis and treatment of this disease reduces the mortality and morbidity associated with cytomegalovirus. For this reason, screen testing for CMV infection in high risk patients including patients with cancer and preemptive therapy in patients with viremia, for prevention of CMV disease could be considered as a strategy for prevention of CMV infection.

  8. Cytomegalovirus Infection and Coronary Artery Disease: A Single-Center Serological Study in Northwestern Iran

    Directory of Open Access Journals (Sweden)

    Zakieh Rostamzadeh Khameneh

    2016-09-01

    Full Text Available Background: The role of chronic Cytomegalovirus (CMV infection and inflammation in the pathogenesis of atherosclerosis and Coronary Artery Disease (CAD is still not clear. Objectives: This study aimed to explore the seroprevalence of anti-CMV antibodies and inflammatory markers in patients with stable angina who had undergone diagnostic coronary angiography for clinical suspicion of CAD. Patients and Methods: This cross-sectional, descriptive study was conducted on 181 patients with stable angina selected randomly among the patients referred to Seyyedoshohada Heart Hospital of Urmia, Iran for diagnostic coronary angiography between August 2012 and December 2013. The patients were categorized into CAD and non-CAD groups based on their angiographic findings. Then, anti-CMV IgG and IgM antibodies were tested using the Enzyme-Linked Immunosorbent Assay (ELISA method (Diapron, Rome, Italy. Serum C-Reactive Protein (CRP was also measured by a qualitative method (Aniston Kit. Results: Based on angiographic findings, 141 patients (77.9% had atheromatous plaques in their coronary arteries, while coronary arteries were free of any plaques in 40 cases (22.1%. Besides, 99.3% of the patients in the CAD group and all the patients in the non-CAD group were anti-CMV IgG positive. The rate of anti-CMV IgM seropositivity was 11.7% in the CAD group and 13.2% in the non-CAD group (P = 0.78. However, no significant difference was observed between the groups with and without angiographically-documented CAD in terms of CRP seropositivity (64.7% vs. 56.4%, P = 0.34. Conclusions: Regardless of having angiographically-proven CAD, almost all the cases referred for coronary angiography in our study had a previous exposure to CMV infection as determined by the presence of anti-CMV IgG antibodies in their sera. In fact, the results indicated no significant associations between CMV infection and the presence of CAD.

  9. Rises in antibody to human herpesvirus 6 detected by enzyme immunoassay in transplant recipients with primary cytomegalovirus infection.

    OpenAIRE

    Chou, S W; Scott, K M

    1990-01-01

    Immunoglobulin G to human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) in sera from solid organ recipients was measured by an enzyme-linked immunoassay (ELISA) before and after transplant. The HHV-6 ELISA was developed from glycine extracts of HHV-6-infected and uninfected HSB-2 cells. At a serum dilution of 1:500, 80 (91%) of 88 recipients were seropositive for HHV-6 before transplant, while only 14 (16%) were seropositive for CMV. Posttransplant HHV-6 serologic rises were observed in 38 ...

  10. Impact of cytomegalovirus infection, year of transplantation, and donor age on outcomes after liver transplantation for hepatitis C.

    Science.gov (United States)

    Burak, Kelly W; Kremers, Walter K; Batts, Kenneth P; Wiesner, Russell H; Rosen, Charles B; Razonable, Raymund R; Paya, Carlos V; Charlton, Michael R

    2002-04-01

    Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) is almost universal. However, variables that hasten the progression of allograft injury have not been fully defined. Cytomegalovirus (CMV) is a common infection post-LT, and its impact on the course of post-LT HCV infection remains unclear. We investigated the impact of CMV infection on patient and graft outcomes in 93 consecutive HCV-infected liver transplant recipients. Data were collected prospectively, with surveillance cultures for CMV and protocol liver biopsies. CMV infection (defined as isolation of CMV from blood and treatment with ganciclovir) occurred in 25 patients (26.9%). Graft failure (defined as cirrhosis, relisting for LT, re-LT, or death) was significantly more common in CMV-positive compared with CMV-negative patients (52% v 19.1%; P =.002). Fibrosis stage 2 or greater on the 4-month liver biopsy specimen was more common in CMV-infected patients (45% v 16.4%; P =.01). Patients who underwent LT in more recent years had an increased risk for graft failure. Donor and recipient age, CMV infection, and mycophenolate mofetil use were significantly associated with graft failure in a stepwise multivariate analysis. CMV infection occurs in approximately one quarter of HCV-infected liver transplant recipients and is an independent risk factor for graft failure in these patients. Whether CMV mediates this by inducing increased immunosuppression or directly enhancing HCV replication requires further study.

  11. Gastrointestinal manifestations of postnatal cytomegalovirus infection in infants admitted to a neonatal intensive care unit over a five year period.

    Science.gov (United States)

    Cheong, J L Y; Cowan, F M; Modi, N

    2004-07-01

    Sixteen cases of postnatal cytomegalovirus (CMV) infection were identified in a neonatal intensive care unit population over a five year period. Eleven of these infants had gastrointestinal signs at the time of presentation. These ranged from minor and transient (abdominal distension and enteral feed intolerance) to severe and life threatening (protein losing enteropathy, diarrhoea, and hypernatraemic dehydration). An initial diagnosis of necrotising enterocolitis was common, but no infant showed intestinal or hepatic portal pneumatosis. The gestational age of the infants was 24-38 weeks. All had received fresh maternal breast milk. It is suggested that CMV enteritis is added to the spectrum of clinical manifestations of postnatal CMV infection. Signs suggestive of necrotising enterocolitis with atypical features should prompt investigations for CMV infection.

  12. Complete Genome Sequence of Pathogenic Guinea Pig Cytomegalovirus from Salivary Gland Homogenates of Infected Animals

    OpenAIRE

    Yang, Dongmei; Tamburro, Kristen; Dittmer, Dirk; Cui, Xiaohong; McVoy, Michael A.; Hernandez-Alvarado, Nelmary; Schleiss, Mark R.

    2013-01-01

    The sequence of guinea pig cytomegalovirus (GPCMV) was determined by direct sequencing of salivary gland homogenates obtained following sustained, serial in vivo passage of pathogenic virus in guinea pigs. The 233,501-nucleotide salivary gland (SG) genome was noted to have 11 differences compared to the tissue culture-passaged virus, although no variations were noted in putative protein coding sequences.

  13. Cytomegalovirus Infection in Pediatric Hematopoietic Stem Cell Transplantation: Risk Factors for Primary Infection and Cases of Recurrent and Late Infection at a Single Center.

    Science.gov (United States)

    Rowe, R Grant; Guo, Dongjing; Lee, Michelle; Margossian, Steven; London, Wendy B; Lehmann, Leslie

    2016-07-01

    Cytomegalovirus (CMV) infection is a significant source of morbidity and mortality in allogeneic stem cell transplantation (SCT). We identified a cohort of 91 pediatric SCT patients at risk (defined as either donor and/or recipient seropositivity) for CMV infection at our institution. We retrospectively categorized at-risk SCT recipients as those who (1) were at risk of CMV infection in the post-SCT period, (2) had documented CMV infection before SCT, (3) experienced recurrence of post-SCT CMV viremia, or (4) experienced late post-SCT CMV viremia; categories were not mutually exclusive. We analyzed the impact of SCT-related factors on incidence of CMV infection and outcome, and we described the outcome of each of these cohorts. In univariate analysis, recipient CMV seropositivity, use of umbilical cord blood graft, and acute graft-versus-host disease (GVHD) predicted post-SCT CMV viremia, and the effects of acute GVHD (odds ratio, 4.018; 95% confidence interval, 1.032 to 15.643) and CMV seropositivity (odds ratio, 16.525; 95% confidence interval, 2.041 to 133.803) were confirmed in multivariate analysis. Patients with recurrence of post-SCT CMV viremia had a 50% all-cause mortality rate, compared with 12% in all 91 patients. Patients with pre-SCT CMV infection had a high incidence of post-SCT CMV infection but could successfully undergo SCT with antiviral prophylaxis and pre-emptive CMV treatment. All patients with late CMV infection had prior GVHD. Theses findings identify risk factors for post-SCT CMV infection and provide novel descriptions of childhood SCT recipients with pre-SCT, recurrent, and late CMV infection, which may contribute to risk stratification strategies for CMV at-risk patients in pediatric allogeneic SCT. PMID:27090959

  14. Are female daycare workers at greater risk of cytomegalovirus infection? A secondary data analysis of CMV seroprevalence between 2010 and 2013 in Hamburg, Germany

    OpenAIRE

    Stranzinger, Johanna; Kozak, Agnessa; Schilgen, Benjamin; Paris, Diana; Nießen, Thomas; Schmidt, Lutz; Wille, Andreas; Wagner, Norbert L; Nienhaus, Albert

    2016-01-01

    Background: Close contact with asymptomatic children younger than three years is a risk factor for a primary cytomegalovirus (CMV) infection. In pregnant women, such primary infection increases the risk of CMV-induced feto- or embryopathy. Daycare providers have therefore implemented working restrictions for pregnant daycare workers (DCWs) in accordance with legislation and guidelines for maternity protection. However, little is known about the infection risk for DCWs. We therefore compared t...

  15. Activation of nucleotide oligomerization domain 2 (NOD2 by human cytomegalovirus initiates innate immune responses and restricts virus replication.

    Directory of Open Access Journals (Sweden)

    Arun Kapoor

    Full Text Available Nucleotide-binding oligomerization domain 2 (NOD2 is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease.

  16. Effect of [Ca2+]i and Neuronal Mitochondria Transmembrane Potentials in Hippocampus of Murine Cytomegalovirus Infected Mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying; WEN Liangzhen; CHENG Biheng

    2006-01-01

    To explore the effect of [Ca2+]I and neuronal mitochondria transmembrane potentials in hippocampus of murine cytomegalovirus (MCMV) infected mice, newborn Balb/c mice were randomly divided into two groups: a virus inoculated group and a control group. After 56 days, single cell of hippocampus was isolated, and mitochondria transmembrane potentials and the intracellular free calcium level [Ca2+ ]I in hippocampus were measured by means of flow cytometry (FCM).Compared with the control group, the mitochondria transmembrane potentials was decreased (P<0.01) and the intracellular free calcium level [Ca2+]I was increased (P<0.01) in inoculated group.The dysfunction of [Ca2+ ]I and mitochondria transmembrane potentials in hippocampus may play an important role in the functional disorders in CMV-infected CNS.

  17. Rhesus and Human Cytomegalovirus Glycoprotein L Are Required for Infection and Cell-to-Cell Spread of Virus but Cannot Complement Each Other▿

    OpenAIRE

    Bowman, J. Jason; Lacayo, Juan C.; Burbelo, Peter; Fischer, Elizabeth R.; Cohen, Jeffrey I.

    2010-01-01

    Rhesus cytomegalovirus (RhCMV), the homolog of human cytomegalovirus (HCMV), serves as a model for understanding the pathogenesis of HCMV and for developing candidate vaccines. In order to develop a replication-defective virus as a vaccine candidate, we constructed RhCMV with glycoprotein L (gL) deleted. RhCMV gL was essential for viral replication, and virus with gL deleted could only replicate in cells expressing RhCMV gL. Noncomplementing cells infected with RhCMV with gL deleted released ...

  18. A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus.

    Science.gov (United States)

    Coleman, Stewart; Choi, K Yeon; Root, Matthew; McGregor, Alistair

    2016-07-01

    In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107-179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model. PMID:27387220

  19. A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus.

    Science.gov (United States)

    Coleman, Stewart; Choi, K Yeon; Root, Matthew; McGregor, Alistair

    2016-07-01

    In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107-179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model.

  20. UNC93B1 mediates innate inflammation and antiviral defense in the liver during acute murine cytomegalovirus infection.

    Directory of Open Access Journals (Sweden)

    Meredith J Crane

    Full Text Available Antiviral defense in the liver during acute infection with the hepatotropic virus murine cytomegalovirus (MCMV involves complex cytokine and cellular interactions. However, the mechanism of viral sensing in the liver that promotes these cytokine and cellular responses has remained unclear. Studies here were undertaken to investigate the role of nucleic acid-sensing Toll-like receptors (TLRs in initiating antiviral immunity in the liver during infection with MCMV. We examined the host response of UNC93B1 mutant mice, which do not signal properly through TLR3, TLR7 and TLR9, to acute MCMV infection to determine whether liver antiviral defense depends on signaling through these molecules. Infection of UNC93B1 mutant mice revealed reduced production of systemic and liver proinflammatory cytokines including IFN-α, IFN-γ, IL-12 and TNF-α when compared to wild-type. UNC93B1 deficiency also contributed to a transient hepatitis later in acute infection, evidenced by augmented liver pathology and elevated systemic alanine aminotransferase levels. Moreover, viral clearance was impaired in UNC93B1 mutant mice, despite intact virus-specific CD8+ T cell responses in the liver. Altogether, these results suggest a combined role for nucleic acid-sensing TLRs in promoting early liver antiviral defense during MCMV infection.

  1. Human Cytomegalovirus Infection of Tumor Cells Downregulates NCAM (CD56: A Novel Mechanism for Virus-Induced Tumor Invasiveness'

    Directory of Open Access Journals (Sweden)

    Roman A. Blaheta

    2004-07-01

    Full Text Available Pathologic data indicate that human cytomegalovirus (HCMV infection might be associated with the pathogenesis of several human malignancies. However, no definitive evidence of a causal link between HCMV infection and cancer dissemination has been established to date. This study describes the modulation of the invasive behavior of NCAM-expressing tumor cell lines by HCMV. Neuroblastoma (NB cells, persistently infected with the HCMV strain AD169 (UKF-NB-4AD169 and MHH-NB-11AD169, were added to endothelial cell monolayers and adhesion and penetration kinetics were measured. The 140- and 180-kDa isoforms of the adhesion receptor NCAM were evaluated by flow cytometry, Western blot, and reverse transcriptionpolymerase chain reaction (RT-PCR. The relevance of NCAM for tumor cell binding was proven by treating NB with NCAM antisense oligonucleotides or NCAM transfection. HCMV infection profoundly increased the number of adherent and penetrated NB, compared to controls. Surface expression of NCAM was significantly lower on UKF-NB-4AD169 and MHH-NB-11AD169, compared to mock-infected cells. Western-blot and RT-PCR demonstrated reduced protein and RNA levels of the 140- and 180-kDa isoform. An inverse correlation between NCAM expression and adhesion capacity of NB has been shown by antisense and transfection experiments. We conclude that HCMV infection leads to downregulation of NCAM receptors, which is associated with enhanced tumor cell invasiveness.

  2. Dual Requirement of Cytokine and Activation Receptor Triggering for Cytotoxic Control of Murine Cytomegalovirus by NK Cells

    Science.gov (United States)

    Pak-Wittel, Melissa A.; Yang, Liping; Schreiber, Robert D.; Yokoyama, Wayne M.

    2015-01-01

    Natural killer (NK) cells play a critical role in controlling murine cytomegalovirus (MCMV) and can mediate both cytokine production and direct cytotoxicity. The NK cell activation receptor, Ly49H, is responsible for genetic resistance to MCMV in C57BL/6 mice. Recognition of the viral m157 protein by Ly49H is sufficient for effective control of MCMV infection. Additionally, during the host response to infection, distinct immune and non-immune cells elaborate a variety of pleiotropic cytokines which have the potential to impact viral pathogenesis, NK cells, and other immune functions, both directly and indirectly. While the effects of various immune deficiencies have been examined for general antiviral phenotypes, their direct effects on Ly49H-dependent MCMV control are poorly understood. To specifically interrogate Ly49H-dependent functions, herein we employed an in vivo viral competition approach to show Ly49H-dependent MCMV control is specifically mediated through cytotoxicity but not IFNγ production. Whereas m157 induced Ly49H-dependent degranulation, efficient cytotoxicity also required either IL-12 or type I interferon (IFN-I) which acted directly on NK cells to produce granzyme B. These studies demonstrate that both of these distinct NK cell-intrinsic mechanisms are integrated for optimal viral control by NK cells. PMID:26720279

  3. Toll-like receptor 4 is involved in the cell cycle modulation and required for effective human cytomegalovirus infection in THP-1 macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Arcangeletti, Maria-Cristina, E-mail: mariacristina.arcangeletti@unipr.it [Department of Clinical and Experimental Medicine, University of Parma, Parma (Italy); Germini, Diego; Rodighiero, Isabella [Department of Clinical and Experimental Medicine, University of Parma, Parma (Italy); Mirandola, Prisco [Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma (Italy); De Conto, Flora; Medici, Maria-Cristina [Department of Clinical and Experimental Medicine, University of Parma, Parma (Italy); Gatti, Rita [Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma (Italy); Chezzi, Carlo; Calderaro, Adriana [Department of Clinical and Experimental Medicine, University of Parma, Parma (Italy)

    2013-05-25

    Suitable host cell metabolic conditions are fundamental for the effective development of the human cytomegalovirus (HCMV) lytic cycle. Indeed, several studies have demonstrated the ability of this virus to interfere with cell cycle regulation, mainly by blocking proliferating cells in G1 or G1/S. In the present study, we demonstrate that HCMV deregulates the cell cycle of THP-1 macrophages (a cell line irreversibly arrested in G0) by pushing them into S and G2 phases. Moreover, we show that HCMV infection of THP-1 macrophages leads to Toll-like receptor 4 (TLR4) activation. Since various studies have indicated TLR4 to be involved in promoting cell proliferation, here we investigate the possible role of TLR4 in the observed HCMV-induced cell cycle perturbation. Our data strongly support TLR4 as a mediator of HCMV-triggered cell cycle activation in THP-1 macrophages favouring, in turn, the development of an efficient viral lytic cycle. - Highlights: ► We studied HCMV infection impact on THP-1 macrophage cell cycle. ► We analysed the role played by Toll-like receptor (TLR) 4 upon HCMV infection. ► HCMV pushes THP-1 macrophages (i.e. resting cells) to re-enter the cell cycle. ► TLR4 pathway inhibition strongly affects the effectiveness of HCMV replication. ► TLR4 pathway inhibition significantly decreases HCMV-induced cell cycle re-entry.

  4. The use of saliva as a practical and feasible alternative to urine in large-scale screening for congenital cytomegalovirus infection increasesinclusion and detection rates

    Directory of Open Access Journals (Sweden)

    Emanuelle Santos de Carvalho Cardoso

    2015-04-01

    Full Text Available INTRODUCTION: Although urine is considered the gold-standard material for the detection of congenital cytomegalovirus (CMV infection, it can be difficult to obtain in newborns. The aim of this study was to compare the efficiency of detection of congenital CMV infection in saliva and urine samples. METHODS: One thousand newborns were included in the study. Congenital cytomegalovirus deoxyribonucleic acid (DNA was detected by polymerase chain reaction (PCR. RESULTS: Saliva samples were obtained from all the newborns, whereas urine collection was successful in only 333 cases. There was no statistically significant difference between the use of saliva alone or saliva and urine collected simultaneously for the detection of CMV infection. CONCLUSIONS: Saliva samples can be used in large-scale neonatal screening for CMV infection.

  5. Research Progress of Infantile Cytomegalovirus Infection%小儿巨细胞病毒感染的研究进展

    Institute of Scientific and Technical Information of China (English)

    许莉莉

    2014-01-01

    Cytomegalovirus infection is the most common infection in infants. Cytomegalovirus can lead to infection of genitourinary, central nervous system, liver and other systems, infection or death from asymptomatic until serious defects.This paper focuses on the CMV clinical manifestations, pathogenesis,detection method, a comprehensive description of animal models and vaccine development.%巨细胞病毒(cytomegaIovirus,CMV)感染是婴幼儿最常见感染之一,可导致生殖泌尿、中枢神经、肝脏等各系统感染,从无症状感染直到严重缺陷或死亡。本文主要对CMV的临床表现,发病机制,检测方法,动物模型以及疫苗的研发等方面进行综合阐述。

  6. Mouse Cytomegalovirus Crosses the Species Barrier with Help from a Few Human Cytomegalovirus Proteins†

    OpenAIRE

    Tang, Qiyi; Maul, Gerd G

    2006-01-01

    Strong species specificity and similar tropisms suggest mouse cytomegalovirus (mCMV) as a potential vector for transgenes into human cells. We reexamined the dogma that mouse cytomegalovirus cannot productively replicate in human cells and found that mouse cytomegalovirus can produce infectious particles albeit at a level that does not sustain an infection. This finding demonstrates that mouse cytomegalovirus can undergo all processes of its life cycle in human cells but may not be well adapt...

  7. Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant

    Science.gov (United States)

    2016-05-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cytomegalovirus Infection; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Isolated Plasmacytoma of Bone; Monoclonal Gammopathy of Undetermined Significance; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously

  8. Human cytomegalovirus infection inhibits tumor necrosis factor alpha (TNF-alpha) signaling by targeting the 55-kilodalton TNF-alpha receptor.

    Science.gov (United States)

    Baillie, J; Sahlender, D A; Sinclair, J H

    2003-06-01

    Infection with human cytomegalovirus (HCMV) results in complex interactions between viral and cellular factors which perturb many cellular functions. HCMV is known to target the cell cycle, cellular transcription, and immunoregulation, and it is believed that this optimizes the cellular environment for viral DNA replication during productive infection or during carriage in the latently infected host. Here, we show that HCMV infection also prevents external signaling to the cell by disrupting the function of TNFRI, the 55-kDa receptor for tumor necrosis factor alpha (TNF-alpha), one of the receptors for a potent cytokine involved in eliciting a wide spectrum of cellular responses, including antiviral responses. HCMV infection of fully permissive differentiated monocytic cell lines and U373 cells resulted in a reduction in cell surface expression of TNFRI. The reduction appeared to be due to relocalization of TNFRI from the cell surface and was reflected in the elimination of TNF-alpha-induced Jun kinase activity. Analysis of specific phases of infection suggested that viral early gene products were responsible for this relocalization. However, a mutant HCMV in which all viral gene products known to be involved in down-regulation of major histocompatibility complex (MHC) class I were deleted still resulted in relocalization of TNFRI. Consequently, TNFRI relocalization by HCMV appears to be mediated by a novel viral early function not involved in down-regulation of cell surface MHC class I expression. We suggest that upon infection, HCMV isolates the cell from host-mediated signals, forcing the cell to respond only to virus-specific signals which optimize the cell for virus production and effect proviral responses from bystander cells.

  9. Data correlations between gender, cytomegalovirus infection and T cells, NK cells, and soluble immune mediators in elderly humans.

    Science.gov (United States)

    Al-Attar, Ahmad; Presnell, Steven R; Peterson, Charlotte A; Thomas, D Travis; Lutz, Charles T

    2016-09-01

    We describe a cohort of 50 elderly subjects, age at least 70 years. We present gender-specific findings in T lymphocyte markers and soluble immune mediators. We show the correlation between cytomegalovirus infection status with CD56(dim) NK cell responses to a variety of stimuli and with CD56(bright)/CD56(dim) NK cell ratio. We also present the correlation of retinol binding protein (RBP)-4 plasma levels with NK cell responses and we explore the relationship between gender and adiponectin, 25(OH)D (vitamin D), and RBP4 in affecting CD56(dim) NK cell responses. These data are discussed in Al-Attar et al. (2016) [1]. PMID:27508213

  10. Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

    Science.gov (United States)

    Wiener, Jeffrey; Chang, Tiffany S.; Dollard, Sheila C.; Amin, Minal M.; Ellington, Sascha; Kayira, Dumbani; van der Horst, Charles; Jamieson, Denise J.

    2015-01-01

    Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections. PMID:26424831

  11. The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection

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    Jenny Tosca Thom

    2015-11-01

    Full Text Available Tissue-resident memory T cells (TRM reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG most-effectively induces CD8+ and CD4+ TRM cells against murine cytomegalovirus (MCMV, which persists in and spreads from this organ. TRM generation depended on local antigen for CD4+, but not CD8+, TRM cells, highlighting major differences in T cell subset-specific demands for TRM development. CMV-specific CD8+ T cells fail to control virus replication upon primary infection in the SG due to CMV-induced MHC I downregulation in glandular epithelial cells. Using intraglandular infection, we challenge this notion and demonstrate that memory CD8+ T cells confer immediate protection against locally introduced MCMV despite active viral immune evasion, owing to early viral tropism to cells that largely withstand MHC I downregulation. Thus, we unravel a yet-unappreciated role for memory CD8+ T cells in protecting mucosal tissues against CMV infection.

  12. The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8(+) T Cells, Facilitating Protection from Local Cytomegalovirus Infection.

    Science.gov (United States)

    Thom, Jenny Tosca; Weber, Thomas Christian; Walton, Senta Maria; Torti, Nicole; Oxenius, Annette

    2015-11-10

    Tissue-resident memory T cells (TRM) reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG) most-effectively induces CD8(+) and CD4(+) TRM cells against murine cytomegalovirus (MCMV), which persists in and spreads from this organ. TRM generation depended on local antigen for CD4(+), but not CD8(+), TRM cells, highlighting major differences in T cell subset-specific demands for TRM development. CMV-specific CD8(+) T cells fail to control virus replication upon primary infection in the SG due to CMV-induced MHC I downregulation in glandular epithelial cells. Using intraglandular infection, we challenge this notion and demonstrate that memory CD8(+) T cells confer immediate protection against locally introduced MCMV despite active viral immune evasion, owing to early viral tropism to cells that largely withstand MHC I downregulation. Thus, we unravel a yet-unappreciated role for memory CD8(+) T cells in protecting mucosal tissues against CMV infection.

  13. Distinct Glycoprotein O Complexes Arise in a Post-Golgi Compartment of Cytomegalovirus-Infected Cells

    OpenAIRE

    Theiler, Regan N.; Compton, Teresa

    2002-01-01

    Human cytomegalovirus (CMV) glycoproteins H, L, and O (gH, gL, and gO, respectively) form a heterotrimeric disulfide-bonded complex that participates in the fusion of the viral envelope with the host cell membrane. During virus maturation, this complex undergoes a series of intracellular assembly and processing events which are not entirely defined (M. T. Huber and T. Compton, J. Virol. 73:3886-3892, 1999). Here, we demonstrate that gO does not undergo the same posttranslational processing in...

  14. In vivo application of recombinant interleukin 2 in the immunotherapy of established cytomegalovirus infection

    OpenAIRE

    Matthias J Reddehase; Mutter, Wolfgang; Koszinowski, Ulrich H.

    1987-01-01

    We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that in vivo application of recombinant human IL-2 (rhIL-2) can enhance the antiviral effect of a limited number of CD8+T lymphocytes, not only in prophylaxis, but also in therapy, when virus has already colonized host tissues. The observed net effect of IL-2 was consistent with the assumption of daily effector population doublings. The prospects for IL-2-supported immunotherapy of establish...

  15. Diagnosis of cytomegalovirus infections by qualitative and quantitative PCR in HIV infected patients Diagnóstico de infecção por CMV em pacientes infectados pelo HIV utilizando PCR qualitativa e quantitativa

    OpenAIRE

    CUNHA Aldo de Albuquerque; Lauro Juliano MARIN; Aquino, Victor Hugo; Figueiredo, Luiz Tadeu Moraes

    2002-01-01

    A high incidence of cytomegalovirus (CMV) infections is observed in Brazil. These viruses are causatives of significant morbidity and mortality among patients with advanced human immunodeficiency virus (HIV) infection. This work, shows the application of a PCR on determination of CMV load in the buffy coat and plasma. We analyzed the samples of 247 HIV infected patients in order to diagnose CMV infection and disease. We developed a semi-quantitative PCR that amplifies part of the glycoprotein...

  16. Does cytomegalovirus infection contribute to socioeconomic disparities in all-cause mortality?

    Science.gov (United States)

    Feinstein, Lydia; Douglas, Christian E; Stebbins, Rebecca C; Pawelec, Graham; Simanek, Amanda M; Aiello, Allison E

    2016-09-01

    The social patterning of cytomegalovirus (CMV) and its implication in aging suggest that the virus may partially contribute to socioeconomic disparities in mortality. We used Cox regression and inverse odds ratio weighting to quantify the proportion of the association between socioeconomic status (SES) and all-cause mortality that was attributable to mediation by CMV seropositivity. Data were from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994), with mortality follow-up through December 2011. SES was assessed as household income (income-to-poverty ratio ≤1.30;>1.30 to≤1.85;>1.85 to≤3.50;>3.50) and education (high school). We found strong associations between low SES and increased mortality: hazard ratio (HR) 1.80; 95% confidence interval (CI): 1.57, 2.06 comparing the lowest versus highest income groups and HR 1.29; 95% CI: 1.13, 1.48 comparing high school education. 65% of individuals were CMV seropositive, accounting for 6-15% of the SES-mortality associations. Age modified the associations between SES, CMV, and mortality, with CMV more strongly associated with mortality in older individuals. Our findings suggest that cytomegalovirus may partially contribute to persistent socioeconomic disparities in mortality, particularly among older individuals. PMID:27268074

  17. Letermovir and inhibitors of the terminase complex: a promising new class of investigational antiviral drugs against human cytomegalovirus

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    Melendez DP

    2015-08-01

    Full Text Available Dante P Melendez,1,2 Raymund R Razonable1,2 1Division of Infectious Diseases, 2William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA Abstract: Infection with cytomegalovirus is prevalent in immunosuppressed patients. In solid organ transplant and hematopoietic stem cell transplant recipients, cytomegalovirus infection is associated with high morbidity and preventable mortality. Prevention and treatment of cytomegalovirus with currently approved antiviral drugs is often associated with side effects that sometimes preclude their use. Moreover, cytomegalovirus has developed mutations that confer resistance to standard antiviral drugs. During the last decade, there have been calls to develop novel antiviral drugs that could provide better options for prevention and treatment of cytomegalovirus. Letermovir (AIC246 is a highly specific antiviral drug that is currently undergoing clinical development for the management of cytomegalovirus infection. It acts by inhibiting the viral terminase complex. Letermovir is highly potent in vitro and in vivo against cytomegalovirus. Because of a distinct mechanism of action, it does not exhibit cross-resistance with other antiviral drugs. It is predicted to be active against strains that are resistant to ganciclovir, foscarnet, and cidofovir. To date, early-phase clinical trials suggest a very low incidence of adverse effects. Herein, we present a comprehensive review on letermovir, from its postulated novel mechanism of action to the results of most recent clinical studies. Keywords: cytomegalovirus, letermovir, AIC246, terminase, antivirals, transplantation 

  18. Screening for congenital cytomegalovirus infection using newborn urine samples collected on filter paper: feasibility and outcomes from a multicentre study.

    Science.gov (United States)

    Koyano, Shin; Inoue, Naoki; Oka, Akira; Moriuchi, Hiroyuki; Asano, Kimisato; Ito, Yushi; Yamada, Hideto; Yoshikawa, Tetsushi; Suzutani, Tatsuo

    2011-01-01

    Background As congenital cytomegalovirus (CMV) infection causes significant clinical consequences not only at birth but also later as neurological sequelae, it is critical to establish a strategy for screening congenitally infected newborns. Previous studies have identified an insufficient sensitivity in screening methods based on the use of dried blood spots (DBSs). Objectives To evaluate the feasibility of the authors' recently developed method for large-scale screening for congenital CMV infection and to identify risk factors for congenital infection. Methods More than 21 000 newborns were enrolled at 25 sites in six geographically separate areas of Japan. Urine was collected onto filter cards placed in the diapers, which were then analysed by quantitative PCR using the filter disc directly as a template. Clinical and physical findings of the newborns were extracted from their medical records. CMV strains from the cases and their siblings were genetically compared. Viral loads in DBSs obtained from some of the cases were compared with those in the urine filters. Results Congenital CMV infection was identified in 0.31% (95% CI 0.24% to 0.39%) of the newborns, and 30% of the cases (20/66) had typical clinical manifestations and/or showed abnormalities in brain images at birth. Although the positive predictive value of our screening was 94%, the lack of any comparison with a gold standard assay prevented calculation of the negative predictive value. Almost two-thirds of the cases had siblings, a significantly higher frequency than for uninfected newborns. Most of the cases (21/25) excreted CMV strains identical to those of their siblings. CMV DNA was undetectable in three out of 12 retrievable DBS specimens. Conclusions Implementation of an effective large-scale screening programme for congenital CMV infection is feasible. Siblings are the major risk factor for congenital CMV infection, which emphasises the need for education of mothers-to-be as well as vaccine

  19. High incidence of Epstein-Barr virus, cytomegalovirus and human herpesvirus 6 infections in children with cancer

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    Horvath Radek

    2002-01-01

    Full Text Available Abstract Background A prospective single-center study was performed to study infection with lymphotropic herpesviruses (LH Epstein-Barr virus (EBV, cytomegalovirus (CMV and human herpesvirus 6 (HHV-6 in children with cancer. Methods The group of 186 children was examined for the presence of LH before, during and 2 months after the end of anticancer treatment. Serology of EBV and CMV was monitored in all children, serology of HHV-6 and DNA analysis of all three LH was monitored in 70 children. Results At the time of cancer diagnosis (pre-treatment, there was no difference between cancer patients and age-matched healthy controls in overall IgG seropositivity for EBV (68.8% vs. 72.0%; p = 0.47 and CMV (37.6% vs. 41.7%; p = 0.36. During anticancer therapy, primary or reactivated EBV and CMV infection was present in 65 (34.9% and 66 (35.4% of 186 patients, respectively, leading to increased overall post-treatment IgG seropositivity that was significantly different from controls for EBV (86.6% vs. 72.0%; p = 0.0004 and CMV (67.7% vs. 41.7%; p Conclusion EBV, CMV and HHV-6 infections are frequently present during therapy of pediatric malignancy.

  20. Detection of congenital cytomegalovirus infection by real-time polymerase chain reaction analysis of saliva or urine specimens.

    Science.gov (United States)

    Ross, Shannon A; Ahmed, Amina; Palmer, April L; Michaels, Marian G; Sánchez, Pablo J; Bernstein, David I; Tolan, Robert W; Novak, Zdenek; Chowdhury, Nazma; Fowler, Karen B; Boppana, Suresh B

    2014-11-01

    Viral culture of urine or saliva has been the gold standard technique for the diagnosis of congenital cytomegalovirus (CMV) infection. Results of rapid culture and polymerase chain reaction (PCR) analysis of urine and saliva specimens from 80 children were compared to determine the clinical utility of a real-time PCR assay for diagnosis of congenital CMV infection. Results of urine PCR were positive in 98.8% of specimens. Three PCR-positive urine samples were culture negative. Results of saliva PCR and culture were concordant in 78 specimens (97.5%). Two PCR-positive saliva samples were culture negative. These findings demonstrate that PCR performs as well as rapid culture of urine or saliva specimens for diagnosing congenital CMV infection and saliva specimens are easier to collect. Because PCR also offers more rapid turnaround, is unlikely to be affected by storage and transport conditions, has lower cost, and may be adapted to high-throughput situations, it is well suited for targeted testing and large-scale screening for CMV.

  1. Human cytomegalovirus infection leads to elevated levels of transplant arteriosclerosis in a humanized mouse aortic xenograft model.

    Science.gov (United States)

    Abele-Ohl, S; Leis, M; Wollin, M; Mahmoudian, S; Hoffmann, J; Müller, R; Heim, C; Spriewald, B M; Weyand, M; Stamminger, T; Ensminger, S M

    2012-07-01

    Recent findings emphasized an important role of human cytomegalovirus (HCMV) infection in the development of transplant arteriosclerosis. Therefore, the aim of this study was to develop a human peripheral blood lymphocyte (hu-PBL)/Rag-2(-/-) γc(-/-) mouse-xenograft-model to investigate both immunological as well as viral effector mechanisms in the progression of transplant arteriosclerosis. For this, sidebranches from the internal mammary artery were recovered during coronary artery bypass graft surgery, tissue-typed and infected with HCMV. Then, size-matched sidebranches were implanted into the infrarenal aorta of Rag-2(-/-) γc(-/-) mice. The animals were reconstituted with human peripheral blood mononuclear cells (PBMCs) 7 days after transplantation. HCMV-infection was confirmed by Taqman-PCR and immunofluorescence analyses. Arterial grafts were analyzed by histology on day 40 after transplantation. PBMC-reconstituted Rag-2(-/-) γc(-/-) animals showed splenic chimerism levels ranging from 1-16% human cells. After reconstitution, Rag-2(-/-) γc(-/-) mice developed human leukocyte infiltrates in their grafts and vascular lesions that were significantly elevated after infection. Cellular infiltration revealed significantly increased ICAM-1 and PDGF-R-β expression after HCMV-infection of the graft. Arterial grafts from unreconstituted Rag-2(-/-) γc(-/-) recipients showed no vascular lesions. These data demonstrate a causative relationship between HCMV-infection as an isolated risk factor and the development of transplant-arteriosclerosis in a humanized mouse arterial-transplant-model possibly by elevated ICAM-1 and PDGF-R-β expression.

  2. Is human cytomegalovirus infection associated with essential hypertension? A meta-analysis of 11,878 participants.

    Science.gov (United States)

    Wang, Zuoguang; Peng, Xiaoyun; Li, Mei; Jin, Fei; Zhang, Bei; Wang, Hao; Wei, Yongxiang

    2016-05-01

    Human cytomegalovirus (HCMV) has been reported to be highly expressed in essential hypertension (EH), and it has been proposed that HCMV infection may contribute to EH development. However, different studies showed opposite results. The present meta-analysis was performed to investigate the association between HCMV infection and the risk of EH. All relevant literature from 1980 to 2015 was extracted from six electronic databases. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of the association of HCMV infection and risk of EH. Sensitivity analysis and examination for bias were conducted to evaluate cumulative evidence of the association. The random-effect model using the Mantel-Haenszel method was used to give the individual effect-size estimates. Of the 11,878 participants included in this study, there were 3,864 EH patients and 8,014 control subjects. Meta-analysis of nine studies performed in a random-effect model found that EH patients had a higher risk of HCMV infection than normal control subjects (OR = 1.47, 95%CI: 1.13-1.90, P = 0.004; heterogeneity: I(2)  = 66%, P = 0.002). Sensitivity analysis and bias examination showed the overall quality and consistency of the studies to be acceptable. For subgroup analysis, studies of Chinese populations were selected for further analysis. There was a significant association between HCMV infection and EH among Chinese patients (OR = 2.18, 95%CI:1.43-3.31, P = 0.0003) but not among other ethnic groups (OR = 1.11, 95%CI:0.95-1.31, P = 0.19). These findings provide quantitative support for the association between HCMV infection and high risk of EH in individuals of Chinese ethnicity.

  3. CLINICAL AND IMMUNOLOGICAL FEATURES OF KIDNEY TRANSPLANT RECIPIENTS WITH CYTOMEGALOVIRUS INFECTION MANIFESTATION IN THE EARLY POSTOPERATIVE PERIOD

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    L. V. Limareva

    2013-01-01

    Full Text Available Aim. To optimize the management of postoperative renal allograft recipients through the introduction of methods for predicting risk of manifestation of cytomegalovirus infection on the basis of a comprehensive assessment of the clinical and immunological status. Materials and methods. We retrospectively analyzed the medical records of 303 patients with end-stage renal disease, among them – were the recipients of renal allograft – 136, among whom 29 within 2 months after the operation had clinical signs of CMV infection. Assessable "CMV syndrome", laboratory evidence of CMV infection, the incidence of antigens (genes of HLA A, B and DRB *1, calculated goodness of fit χ2 and relative risk RR, changes MCP-1 in urine. Results. In renal allograft recipients with clinical and laboratory evidence of CMV infection in the early postoperative period, significantly more (χ2 > 3,8 met antigen B35. A positive association with CMV infection was detected also for DRB1 * 08, B21, B22, B41, A24 (9, B51 (5, DRB1*14 and DRB1*15. Protective effects possessed antigens / alleles of genes A26 (10, B14, B38 (16 B61 (40 and DRB1*16. MCP-1 levels in this group of recipients were raised to 2174,7 ± 296,3 pg/ml with a strong negative correlation with the levels of urea and creatinine in serum (r = 0,9, p < 0.001. Conclusion. Immunological markers of risk manifestation of CMV infection in recipients of kidneys in the early postoperative period are: the carriage of В35 и В55,56(22, В49(21, В41, DRB1*08 и DRB1*15, an increase of levels of MCP-1 in urine without increasing the levels of urea and creatinine in the serum. 

  4. Comparison of conventional, immunological and molecular techniques for the diagnosis of symptomatic congenital human cytomegalovirus infection in neonates and infants

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    A Choudhary

    2015-01-01

    Full Text Available Purpose: Human cytomegalovirus (HCMV is the commonest pathogen causing congenital infection globally. The diagnosis of congenital infection is based either on viral isolation (in cell culture or demonstration of HCMV DNA from the urine. Saliva is also being used as an alternative sample to urine for the same. The objective of this study was to compare the following assays-polymerase chain reaction (PCR from urine, saliva and blood, serology (anti-HCMV IgM and antigen detection (HCMV pp65 antigenaemia for the diagnosis of congenital HCMV infection. Materials and Methods: Urine and blood samples were collected from 31 infants (median age: 13 weeks with suspected HCMV infection. For 18 infants, additional saliva samples were collected and all the above assays were compared. Results: PCR for HCMV DNA from urine and anti-HCMV IgM were performed for all 31 infants. Of these, 22 (70.9% were positive for both assays. In 18 (of the 22 infants positive by both assays, PCR for HCMV DNA from saliva was positive in all 18 (100%, PCR from blood in 7/18 (38.8% and HCMV pp65 antigenaemia only in 1/18 (5.5% of the infants. Conclusion: Detection of HCMV DNA in urine combined with anti-HCMV IgM are suitable assays to diagnose HCMV infection in infants. Both PCR from the blood and HCMV pp65 antigenaemia lack sensitivity in infants. Salivary PCR combines convenience with high sensitivity and can substitute PCR from urine, especially in the outpatient and field settings. To the best of our knowledge, this is the first study from India to evaluate salivary PCR for the diagnosis of congenital HCMV infection.

  5. Cis and trans acting factors involved in human cytomegalovirus experimental and natural latent infection of CD14 (+ monocytes and CD34 (+ cells.

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    Cyprian C Rossetto

    Full Text Available The parameters involved in human cytomegalovirus (HCMV latent infection in CD14 (+ and CD34 (+ cells remain poorly identified. Using next generation sequencing we deduced the transcriptome of HCMV latently infected CD14 (+ and CD34 (+ cells in experimental as well as natural latency settings. The gene expression profile from natural infection in HCMV seropositive donors closely matched experimental latency models, and included two long non-coding RNAs (lncRNAs, RNA4.9 and RNA2.7 as well as the mRNAs encoding replication factors UL84 and UL44. Chromatin immunoprecipitation assays on experimentally infected CD14 (+ monocytes followed by next generation sequencing (ChIP-Seq were employed to demonstrate both UL84 and UL44 proteins interacted with the latent viral genome and overlapped at 5 of the 8 loci identified. RNA4.9 interacts with components of the polycomb repression complex (PRC as well as with the MIE promoter region where the enrichment of the repressive H3K27me3 mark suggests that this lncRNA represses transcription. Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE, which identifies nucleosome-depleted viral DNA, was used to confirm that latent mRNAs were associated with actively transcribed, FAIRE analysis also showed that the terminal repeat (TR region of the latent viral genome is depleted of nucleosomes suggesting that this region may contain an element mediating viral genome maintenance. ChIP assays show that the viral TR region interacts with factors associated with the pre replication complex and a plasmid subclone containing the HCMV TR element persisted in latently infected CD14 (+ monocytes, strongly suggesting that the TR region mediates viral chromosome maintenance.

  6. Aminobisphosphonates Synergize with Human Cytomegalovirus To Activate the Antiviral Activity of Vγ9Vδ2 Cells.

    Science.gov (United States)

    Daguzan, Charline; Moulin, Morgane; Kulyk-Barbier, Hanna; Davrinche, Christian; Peyrottes, Suzanne; Champagne, Eric

    2016-03-01

    Human Vγ9Vδ2 T cells are activated through their TCR by neighboring cells producing phosphoantigens. Zoledronate (ZOL) treatment induces intracellular accumulation of the phosphoantigens isopentenyl pyrophosphate and ApppI. Few attempts have been made to use immunomanipulation of Vγ9Vδ2 lymphocytes in chronic viral infections. Although Vγ9Vδ2 T cells seem to ignore human CMV (HCMV)-infected cells, we examined whether they can sense HCMV when a TCR stimulus is provided with ZOL. Fibroblasts treated with ZOL activate Vγ9Vδ2 T cells to produce IFN-γ but not TNF. Following the same treatment, HCMV-infected fibroblasts stimulate TNF secretion and an increased production of IFN-γ, indicating that Vγ9Vδ2 cells can sense HCMV infection. Increased lymphokine production was observed with most clinical isolates and laboratory HCMV strains, HCMV-permissive astrocytoma, or dendritic cells, as well as "naive" and activated Vγ9Vδ2 cells. Quantification of intracellular isopentenyl pyrophosphate/ApppI following ZOL treatment showed that HCMV infection boosts their accumulation. This was explained by an increased capture of ZOL and by upregulation of HMG-CoA synthase and reductase transcription. Using an experimental setting where infected fibroblasts were cocultured with γδ cells in submicromolar concentrations of ZOL, we show that Vγ9Vδ2 cells suppressed substantially the release of infectious particles while preserving uninfected cells. Vγ9Vδ2 cytotoxicity was decreased by HCMV infection of targets whereas anti-IFN-γ and anti-TNF Abs significantly blocked the antiviral effect. Our experiments indicate that cytokines produced by Vγ9Vδ2 T cells have an antiviral potential in HCMV infection. This should lead to in vivo studies to explore the possible antiviral effect of immunostimulation with ZOL in this context. PMID:26819204

  7. Antibody therapeutics for prevention and treatment of human cytomegalovirus infection%防治人巨细胞病毒感染的抗体类药物

    Institute of Scientific and Technical Information of China (English)

    向思龙; 马玉媛; 余蓉; 章金刚

    2013-01-01

    Human cytomegalovirus (HCMV) has drawn considerable attention because it congenitally infects newborns and causes lethal diseases in the immunocompromised, including organ or stem cell transplant recipients, and patients with AIDS. Chemical drugs including ganciclovir are the major approach for HCMV prevention and treatment. Meannhile, HCMV-specific antibody therapeutics is also an effective treatment and prevention strategy for HCMV infection and disease. HCMV-specific antibody therapeutics has the capacity to neutralize virus, activate complement and mediate opsonization, and shows promising results for the treatment and prevention of HCMV infection. This review outlines the development, and clinical applications of cytomegalovirus-specific antibody therapeutics including HCMV hyperimmune globulin and HCMV-specific monoclonal antibodies.%人巨细胞病毒因易造成婴幼儿先天性感染、免疫抑制(器官/干细胞移植受体和重度艾滋病等)患者致死性并发症而备受关注.更昔洛韦等化学药物是目前防治巨细胞病毒感染的主要药物,同时,巨细胞病毒特异性的抗体类药物也是防治巨细胞病毒感染的努力方向之一.巨细胞病毒特异性的抗体类药物具有较强病毒中和能力,且可激活补体并介导调理作用,被证明为防治巨细胞病毒感染的有效被动免疫制剂.本文主要就巨细胞病毒感染的抗体类药物,即巨细胞病毒免疫球蛋白和巨细胞病毒特异的治疗性工程化抗体的研制、临床应用及目前存在问题进行综述.

  8. Increased carotid intima-media thickness associated with antibody responses to varicella-zoster virus and cytomegalovirus in HIV-infected patients.

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    Mar Masiá

    Full Text Available OBJECTIVE: We investigated the relationship of the Herpesviridiae with inflammation and subclinical atherosclerosis in HIV-infected patients. METHODS: Prospective study including virologically suppressed HIV-infected patients. IgG antibodies against herpesviruses, carotid intima-media thickness (cIMT, endothelial function through flow-mediated dilatation (FMD of the brachial artery, and blood atherosclerosis biomarkers (hsCRP, TNF-α, IL-6, MCP-1, MDA, sCD14, sCD163, VCAM-1, ICAM-1, D-dimer, and PAI-1 were measured. RESULTS: 136 patients with HIV viral load <200 copies/ml were included. 93.4% patients were infected with herpes simplex virus type-1, 55.9% with herpes simplex virus type-2, 97.1% with varicella-zoster virus, 65.4% with human herpesvirus-6, 91.2% with cytomegalovirus, and 99.3% with Epstein-Barr virus. Previous AIDS diagnosis was associated with higher cytomegalovirus IgG titers (23,000 vs 17,000 AU, P = 0.011 and higher varicella-zoster virus IgG titers (3.19 vs 2.88 AU, P = 0.047, and there was a positive correlation of the Framingham risk score with IgG levels against cytomegalovirus (Spearman's Rho 0.216, P = 0.016 and Herpes simplex virus-2 (Spearman's Rho 0.293, P = 0.001. IgG antibodies against cytomegalovirus correlated in adjusted analysis with the cIMT (P = 0.030. High seropositivity for varicella-zoster virus (OR 2.91, 95% CI 1.05-8.01, P = 0.039, and for cytomegalovirus (OR 3.79, 95% CI 1.20-11.97, P = 0.023 were predictors for the highest quartile of the cIMT in adjusted analyses. PAI-1 levels were independently associated with cytomegalovirus IgG titers (P = 0.041, IL-6 and ICAM-1 levels with varicella-zoster virus IgG (P = 0.046 and P = 0.035 respectively, and hsCRP levels with Herpes simplex virus-2 IgG (P = 0.035. CONCLUSION: In virologically suppressed HIV-infected patients, antibody responses against herpesviruses are associated with subclinical atherosclerosis, and with increased inflammation and coagulation

  9. Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection

    Science.gov (United States)

    Marzi, Andrea; Murphy, Aisling A.; Feldmann, Friederike; Parkins, Christopher J.; Haddock, Elaine; Hanley, Patrick W.; Emery, Matthew J.; Engelmann, Flora; Messaoudi, Ilhem; Feldmann, Heinz; Jarvis, Michael A.

    2016-01-01

    Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity. PMID:26876974

  10. Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection.

    Science.gov (United States)

    Marzi, Andrea; Murphy, Aisling A; Feldmann, Friederike; Parkins, Christopher J; Haddock, Elaine; Hanley, Patrick W; Emery, Matthew J; Engelmann, Flora; Messaoudi, Ilhem; Feldmann, Heinz; Jarvis, Michael A

    2016-02-15

    Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity.

  11. Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact.

    Science.gov (United States)

    Fornara, O; Bartek, J; Rahbar, A; Odeberg, J; Khan, Z; Peredo, I; Hamerlik, P; Bartek, J; Stragliotto, G; Landázuri, N; Söderberg-Nauclér, C

    2016-02-01

    Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co-expression of these two proteins predicted poor patient survival. Infection of GBM cells with HCMV led to upregulation of CD133 and other GSCS markers (Notch1, Sox2, Oct4, Nestin). HCMV infection also promoted the growth of GBM cells as neurospheres, a behavior typically displayed by GCSCs, and this phenotype was prevented by either chemical inhibition of the Notch1 pathway or by treatment with the anti-viral drug ganciclovir. GBM cells that maintained expression of HCMV-IE failed to differentiate into neuronal or astrocytic phenotypes. Our findings imply that HCMV infection induces phenotypic plasticity of GBM cells to promote GCSC features and may thereby increase the aggressiveness of this tumor. PMID:26138445

  12. Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection.

    Science.gov (United States)

    Goodier, Martin R; Rodriguez-Galan, Ana; Lusa, Chiara; Nielsen, Carolyn M; Darboe, Alansana; Moldoveanu, Ana L; White, Matthew J; Behrens, Ron; Riley, Eleanor M

    2016-07-01

    Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2-dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV(-)) individuals than in HCMV-seropositive (HCMV(+)) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV(+) and HCMV(-) subjects. In addition to these IL-2-dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57(-) NK cells and was most evident in HCMV(+) subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection. PMID:27233958

  13. Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection

    Science.gov (United States)

    Goodier, Martin R.; Rodriguez-Galan, Ana; Lusa, Chiara; Nielsen, Carolyn M.; Darboe, Alansana; Moldoveanu, Ana L.; White, Matthew J.; Behrens, Ron

    2016-01-01

    Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2–dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV−) individuals than in HCMV-seropositive (HCMV+) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV+ and HCMV− subjects. In addition to these IL-2–dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57− NK cells and was most evident in HCMV+ subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection. PMID:27233958

  14. Human Cytomegalovirus Infection in Women of Childbearing Age Throughout Fars Province - Iran: A Population-based Cohort Study

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    Arabpour, M.

    2007-01-01

    Full Text Available Human cytomegalovirus (hCMV has been described as an important etiological agent of intrauterine infection in women of childbearing age that causes congenital malformation. In the present study we examined 844 serum samples from women of child-bearing age for the presence of IgM and IgG antibodies against hCMV by Elisa technique. 764 out of 844 (93% of the cases were seropositive for hCMV-IgG and 45 (5.4% cases were seropositive for hCMV-IgM. An increase in the rate of IgG seroprevalance was associated with an increase in age and parity. The IgG seroprevalance rate was inversely proportional to increasing abortions. Intrestingly seasonal variation affected IgG seroprevalance. There was an increasing trend in IgM positivity rate with age in women less than 29 years. hCMV seroprevalence rate was higher in women from rural as compared to those of urban areas. Finally hCMV primary infections occured in 2.4 % of all pregnancis and it is estimated that up to 0.3% of all congenital disorders, through out Fars province, were due to hCMV. We suggest a role of child to mother hCMV transmission and sexual maturity as the most probable epidemiological factors of hCMV seroprevalence among women of child bearing age.

  15. Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on the health of infants born to HIV-infected mothers

    Science.gov (United States)

    Chang, Tiffany S.; Wiener, Jeffrey; Dollard, Sheila C.; Amin, Minal M.; Ellington, Sascha; Chasela, Charles; Kayira, Dumbani; Tegha, Gerald; Kamwendo, Deborah; Jamieson, Denise J.; van der Horst, Charlie; Kourtis, Athena P.

    2015-01-01

    Background Cytomegalovirus (CMV) infection can be acquired in utero or postnatally through horizontal transmission and breastfeeding. The effect of postnatal CMV infection on postnatal HIV transmission is unknown. Methods The Breastfeeding, Antiretrovirals and Nutrition study, conducted in Malawi, randomized 2369 mothers and their infants to three antiretroviral prophylaxis arms –mother (triple regimen), infant (nevirapine), or neither – for 28 weeks of breastfeeding, followed by weaning. Stored plasma and peripheral blood mononuclear cell specimens were available for 492 infants at 24 weeks and were tested with CMV PCR. Available samples from infants who were CMV PCR-positive at 24 weeks were also tested at birth (N = 242), and from infants PCR-negative at 24 weeks were tested at 48 weeks (N = 96). Cox proportional-hazards models were used to determine if CMV infection was associated with infant morbidity, mortality, or postnatal HIV acquisition. Results At 24 weeks of age, CMV DNA was detected in 345/492 infants (70.1%); the estimated congenital CMV infection rate was 2.3%, and the estimated rate of CMV infection at 48 weeks was 78.5%. CMV infection at 24 weeks was associated with subsequent HIV acquisition through breastfeeding or infant death between 24 and 48 weeks of age (hazard ratio 4.27, P = 0.05). Conclusion Most breastfed infants of HIV-infected mothers in this resource-limited setting are infected with CMV by 24 weeks of age. Early CMV infection may be a risk factor for subsequent infant HIV infection through breastfeeding, pointing to the need for comprehensive approaches in order to achieve elimination of breastfeeding transmission of HIV. PMID:25985405

  16. Cytomegalovirus infection does not impact on survival or time to first treatment in patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Parry, Helen Marie; Damery, Sarah; Hudson, Christopher; Maurer, Matthew J; Cerhan, James R; Pachnio, Annette; Begum, Jusnara; Slager, Susan L; Fegan, Christopher; Man, Stephen; Pepper, Christopher; Shanafelt, Tait D; Pratt, Guy; Moss, Paul A H

    2016-08-01

    Human cytomegalovirus (HCMV) is a widely prevalent herpes virus which establishes a state of chronic infection. The establishment of CMV-specific immunity controls viral reactivation and leads to the accumulation of very large numbers of virus-specific T cells which come to dominate the immune repertoire. There is concern that this may reduce the immune response to heterologous infections and HCMV infection has been associated with reduced survival in elderly people. Patients with chronic lymphocytic leukemia (B-CLL) suffer from a state of immune suppression but have a paradoxical increase in the magnitude of the CMV-specific T cell and humoral immune response. As such, there is now considerable interest in how CMV infection impacts on the clinical outcome of patients with B-CLL. Utilizing a large prospective cohort of patients with B-CLL (n = 347) we evaluated the relationship between HCMV seropositivity and patient outcome. HCMV seropositive patients had significantly worse overall survival than HCMV negative patients in univariate analysis (HR = 2.28, 95% CI: 1.34-3.88; P = 0.002). However, CMV seropositive patients were 4 years older than seronegative donors and this survival difference was lost in multivariate modeling adjusted for age and other validated prognostic markers (P = 0.34). No significant difference was found in multivariate modeling between HCMV positive and negative patients in relation to the time to first treatment (HR = 1.12, 95% CI: 0.68-1.84; P = 0.65). These findings in a second independent cohort of 236 B-CLL patients were validated. In conclusion no evidence that HCMV impacts on the clinical outcome of patients with B-CLL was found. Am. J. Hematol. 91:776-781, 2016. © 2016 Wiley Periodicals, Inc. PMID:27124884

  17. Cytomegalovirus Infection during Pregnancy and Its Impact on the Intrauterine Fetal Development – Case Report

    Directory of Open Access Journals (Sweden)

    Mariya Angelova Angelova

    2016-08-01

    CONCLUSIONS: In the described case the time interval between infection and ultrasonic manifestations is more than 17 weeks. The long interval between infection and occurrence of ultrasound markers can be a good prediction sign, as it may reflect less aggressive viral infection than present in cases where similar ultrasound findings were obtained shortly after infection of the mother.

  18. 烧伤患者巨细胞病毒复发感染对预后影响的临床研究%Clinical study on effect of recurrent cytomegalovirus infections on the prognosis of burn patients

    Institute of Scientific and Technical Information of China (English)

    谭静雷; 张帆; 王芳

    2015-01-01

    OBJECTIVE To investigate the effect of recurrent cytomegalovirus infections on the prognosis of burn patients as well as cytomegalovirus resistance to antiviral drugs ,so as to provide the basis for clinical treatment . METHODS A total of 132 cases were selected whose total burn area was ≥ 15% and cytomegalovirus (HCMV) IgG antibody was positive during Apr .2011 to Oct .2013 .According to whether HCMV‐DNA was positive ,the patients were divided into group A (positive) and group B (negative) .Two groups of patients were summarized by sepsis incidence and survival rate .The software SPSS13 .0 was used for statistical analysis of data .RESULTS The occurrence of sepsis was 57 .97% in group A and 22 .22% in group B ,indicating the sepsis incidence was higher in group A than in group B ,the difference was significant (P<0 .05) .The survival rate was 84 .06% in group A and 95 .25% in group B ,indicating that the survival rate was significantly lower in group A than in group B (P<0 .05) .CONCLUSION The sepsis incidence and mortality is high and the prognosis is poor in burn patients with recurrent cytomegalovirus infections .Therefore ,for burn patients ,it is suggested to actively prevent recurrence of cytomegalovirus infections and give sensitive anti‐viral agents once cytomegalovirus infection occurs .%目的:探讨烧伤患者巨细胞病毒复发感染对预后的影响,以及巨细胞病毒对抗病毒药物的耐药性,为临床治疗提供依据。方法选取2011年4月-2013年10月烧伤总面积≥15%且巨细胞病毒(HCM V )IgG抗体阳性患者132例,根据其HCMV‐DNA是否阳性将其分为A、B两组,其中A组为HCMV‐DNA阳性,B组为阴性;对两组患者脓毒血症发生率以及存活率进行统计,数据采用SPSS13.0进行统计分析。结果患者发生脓毒血症的发生率A组为57.97%、B组为22.22%,A组患者脓毒血症发生率明显高于B组,两组比较差异有统计学意义( P<0

  19. Natural history of cytomegalovirus infection in a series of patients diagnosed with moderate-severe ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Valeria Criscuoli; Maria Rosa Rizzuto; Luigi Montalbano; Elena Gallo; Mario Cottone

    2011-01-01

    AIM: To evaluate the natural history of human cytomegalovirus (HCMV) infection in a series of 28 ulcerative colitis patients in whom the search for HCMV was positive.METHODS: A series of 85 patients with moderate-severe ulcerative colitis flare-up were evaluated for a HCMV search by performing a haematoxylin and eosin stain,immunohistochemical assay and nested polymerase chain reaction on rectal biopsies. Among 85 screened patients (19 of whom were steroid resistant/dependant),28 were positive for HCMV; after remission the patients were followed up clinically and histologically.RESULTS: Among the 22 patients with complete followup,in 8 (36%) patients HCMV-DNA persisted in the intestinal specimens. Among the HCMV positive patients,4 (50%) experienced at least one moderate-severe flare-up of colitis without evidence of peripheral HCMV.Among the 14 HCMV negative patients, 3 with pouches developed pouchitis and 5 out of 11 (45%) experienced a colitis flare-up.CONCLUSION: Our preliminary results suggest that HCMV may remain in the colon after an acute colitis flareup despite remission; it seems that the virus is not responsible for the disease relapse.

  20. Xenotransplantation and porcine cytomegalovirus.

    Science.gov (United States)

    Denner, Joachim

    2015-01-01

    Porcine microorganisms may be transmitted to the human recipient when xenotransplantation with pig cells, tissues, and organs will be performed. Most of such microorganisms can be eliminated from the donor pig by specified or designated pathogen-free production of the animals. As human cytomegalovirus causes severe transplant rejection in allotransplantation, considerable concern is warranted on the potential pathogenicity of porcine cytomegalovirus (PCMV) in the setting of xenotransplantation. On the other hand, despite having a similar name, PCMV is different from HCMV. The impact of PCMV infection on pigs is known; however, the influence of PCMV on the human transplant recipient is unclear. However, first transplantations of pig organs infected with PCMV into non-human primates were associated with a significant reduction of the survival time of the transplants. Sensitive detection methods and strategies for elimination of PCMV from donor herds are required.

  1. Valganciclovir for the prophylaxis and treatment of cytomegalovirus infection in solid organ transplantation

    Directory of Open Access Journals (Sweden)

    Erin Wade Ticehurst

    2010-03-01

    Full Text Available Erin Wade Ticehurst1, Jennifer Trofe-Clark1,2, Emily Blumberg3, Roy D Bloom21Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA; 2Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; 3Infectious Diseases Division, University of Pennsylvania, Philadelphia, Pennsylvania, USAAbstract: Cytomegalovirus (CMV can be a problematic virus for solid organ transplant recipients affecting both morbidity and mortality. Valganciclovir (VGC is a commonly utilized antiviral agent for the prevention of this virus post-transplantation and recently it has been evaluated for the treatment of CMV. It is a pro-drug of ganciclovir (GCV and has increased bioavailability compared to GCV. It is unclear whether VGC is superior to intravenous or oral GCV in terms of efficacy and safety in the prevention of CMV particularly in the liver transplant population as there have been studies reporting inferiority while other studies have not. Despite this, VGC has been reported to be the most commonly utilized agent for CMV prophylaxis in the liver transplant population in the United States and Canada. This article reviews CMV and VGC in the context of solid organ transplant, describes and assesses selected studies that have been conducted using this agent in this patient population, and summarizes VGC’s advantages and disadvantages. Additional studies are needed to further define VGC’s role in the treatment of CMV in the solid organ transplantation population as there are an insufficient number of studies pertaining to CMV treatment and no studies have been performed to assess its role in the treatment of life-threatening CMV disease. VGC is non-inferior to GCV for CMV prevention in the solid organ transplant population with the exception of liver transplant recipients.Keywords: transplant, antiviral therapy, valganciclovir

  2. Congenital Cytomegalovirus Infection Manifesting as Neonatal Persistent Pulmonary Hypertension: Report of Two Cases

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    Elizabeth Walter-Nicolet

    2011-01-01

    Conclusion: Neonatal persistent pulmonary hypertension can be the consequence of congenital CMV infection. Intensive respiratory support and IV ganciclovir are indicated in case of life-threatening condition.

  3. Human cytomegalovirus IE1 protein elicits a type II interferon-like host cell response that depends on activated STAT1 but not interferon-γ.

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    Theresa Knoblach

    2011-04-01

    Full Text Available Human cytomegalovirus (hCMV is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1 protein, a major transcriptional activator and antagonist of type I interferon (IFN signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-γ and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1 and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis nor secretion of IFN-γ or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity.

  4. Progressive hearing loss following acquired cytomegalovirus infection in an immunocompromised child.

    Science.gov (United States)

    Kato, Ken; Otake, Hironao; Tagaya, Mitsuhiko; Takahashi, Yoshiyuki; Ito, Yoshinori; Hama, Asahito; Muramatsu, Hideki; Kojima, Seiji; Naganawa, Shinji; Nakashima, Tsutomu

    2013-01-01

    We report a rare case of progressive hearing loss after acquired CMV infection in a child with Langerhans cell histiocytosis (LCH). A 5-month-old female was diagnosed as having LCH. When she was 14 months old, she received an unrelated donor umbilical cord blood transfusion for the treatment of intractable LCH. CMV infection was confirmed after the blood transfusion. Because her own umbilical cord had no CMV, the CMV infection was not congenital. When she was 7 years old, mixed hearing loss was noted with bilateral otitis media with effusion. After that time, the sensorineural hearing loss progressed to bilateral profound hearing loss over 3 years. Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging with gadolinium contrast enhancement revealed a high intensity area in the inner ear that suggested bilateral labyrinthitis. This case demonstrates the possibility that, under the immunodeficiency, the acquired CMV infection causes progressive sensorineural hearing loss.

  5. Incidence and Risk of Cytomegalovirus Infection during Pregnancy in an Urban Area of Northern Italy

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    Massimo De Paschale

    2009-01-01

    Full Text Available The fetal consequences of CMV infection make it one of the most serious infections contracted during pregnancy, but the scientific community is divided over the proposed implementation of preventive screening for anti-CMV antibodies. The aim of this study was to assess the incidence and risk of infection during pregnancy in 2817 women who underwent anti-CMV IgG and IgM antibody screening during the period 2005–2007. The prevalence of anti-CMV IgG antibodies was 68.3% (95% CI: 66.6–70.0; the seroconversion rate in the 892 seronegative women was 0.32%; the results of IgG avidity testing revealed an cumulative incidence of 1.4% (95% CI: 0.97–1.83, density incidence of 0.8% (as cases/pregnant woman-trimester (95% CI: 0.47–1.13, and a risk of infection of 0.5% (95% CI: 0.24–0.76. The screening identified 13 cases of primary infection (84.6% of which occurred in the first trimester of pregnancy. The possibility to identify these cases and consequently to plan appropriate interventions, supports the use of screening during pregnancy, especially in the first trimester when the risk of infection is greater.

  6. Kinetics of specific immunoglobulins M, E, A, and G in congenital, primary, and secondary cytomegalovirus infection studied by antibody-capture enzyme-linked immunosorbent assay.

    OpenAIRE

    Nielsen, S L; Sørensen, I; Andersen, H K

    1988-01-01

    Antibody-capture enzyme-linked immunosorbent assay (ELISA) using enzyme-labeled cytomegalovirus (CMV) nuclear antigen is a reliable and easily performed test suitable for routine use. As the serologic response to CMV infection may, however, vary considerably among patients, we have studied the kinetics of CMV-specific immunoglobulin M (IgM), IgE, IgA, and IgG antibodies in 352 sera from 61 patients by using antibody-capture ELISA and complement fixation (CF) tests. In a CMV mononucleosis grou...

  7. Cytomegalovirus infection in patients with sepsis due to bloodstream infections: lower risk and better outcomes in new versus already hospitalised intensive care unit admissions.

    Science.gov (United States)

    R, Osawa; M, Wagener; Ns, Singh

    2016-09-01

    Few studies have examined cytomegalovirus (CMV) reactivation exclusively in immunocompetent patients with sepsis due to bloodstream infections. In a cohort of CMV-seropositive critically ill otherwise non-immunosuppressed patients with sepsis due to bloodstream infection, weekly testing for CMV viraemia was performed. Outcomes were assessed at 30 days or until death/discharge from the intensive care unit (ICU). CMV viraemia developed in 20% (20/100) of the patients. Age (P=0.044) and blood transfusions (P=0.022) were significantly associated with CMV viraemia. There was no difference in the primary endpoint (mortality and/or multi-organ failure) between patients with and without CMV viraemia (P=0.49). However, CMV viraemia was associated with significantly fewer ICU-free days (P=0.023) and fewer ventilator-free days (P=0.031). Patients hospitalised in the ICU for more than 48 hours prior to the onset of bloodstream infection were more likely to develop CMV viraemia (P=0.006), have high-grade viraemia (P=0.010), and fewer ICU-free days (P=0.018) and ventilator-free days (P=0.029) than those admitted within 48 hours of bloodstream infection. Thus, CMV reactivation was associated with fewer ICU- and ventilator-free days, however overall mortality was not affected. Patients already in the ICU at the onset of sepsis had higher risk of CMV reactivation and worse outcomes than new ICU-bound patients suggesting that a targeted approach for interventions for CMV could conceivably be directed towards those with a more protracted course of illness. PMID:27608339

  8. Cytomegalovirus Infection Reduces Telomere Length of the Circulating T Cell Pool

    NARCIS (Netherlands)

    P.J.E.J. van de Berg; S.J. Griffiths; S.L. Yong; R. Macaulay; F.J. Bemelman; S. Jackson; S.M. Henson; R.J.M. ten Berge; A.N. Akbar; R.A.W. van Lier

    2010-01-01

    Short telomeres of circulating leukocytes are a risk factor for age-related diseases, such as atherosclerosis, but the exact mechanisms generating variations in telomere length are unknown. We hypothesized that induction of differentiated T cells during chronic CMV infection would affect T cell telo

  9. Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium.

    Science.gov (United States)

    Pachnio, Annette; Ciaurriz, Miriam; Begum, Jusnara; Lal, Neeraj; Zuo, Jianmin; Beggs, Andrew; Moss, Paul

    2016-09-01

    Cytomegalovirus (CMV) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people. Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-peptide tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a range of HLA class II-peptide tetramers to investigate the phenotypic and transcriptional profile of CMV-specific CD4+ T cells within healthy donors. We show that such cells comprise an average of 0.45% of the CD4+ T cell pool and can reach up to 24% in some individuals (range 0.01-24%). CMV-specific CD4+ T cells display a highly differentiated effector memory phenotype and express a range of cytokines, dominated by dual TNF-α and IFN-γ expression, although substantial populations which express IL-4 were seen in some donors. Microarray analysis and phenotypic expression revealed a profile of unique features. These include the expression of CX3CR1, which would direct cells towards fractalkine on activated endothelium, and the β2-adrenergic receptor, which could permit rapid response to stress. CMV-specific CD4+ T cells display an intense cytotoxic profile with high level expression of granzyme B and perforin, a pattern which increases further during aging. In addition CMV-specific CD4+ T cells demonstrate strong cytotoxic activity against antigen-loaded target cells when isolated directly ex vivo. PD-1 expression is present on 47% of cells but both the intensity and distribution of the inhibitory receptor is reduced in older people. These findings reveal the marked accumulation and unique phenotype of CMV-specific CD4+ T cells and indicate how such T cells may contribute to the vascular complications associated with CMV in older people. PMID:27606804

  10. Cytomegalovirus Infection during Pregnancy and Its Impact on the Intrauterine Fetal Development – Case Report

    Science.gov (United States)

    Angelova, Mariya; Kovachev, Emil; Todorov, Nikolai

    2016-01-01

    AIM: The aim of this publication is to present a case of CMV infection during pregnancy, with clinical manifestations of the development of microcephaly and simultaneous dilatation of the 3rd and 4th brain ventricle at 23 weeks gestation. This article discusses the role of ultrasound screening in the second trimester of pregnancy. CASE PRESENTATION: We present the case of a 25-year-old woman with the initials S.K. in her second pregnancy that came to our antenatal Consulting Centre. The first screening for blood count, blood group, biochemistry and serology showed results within the reference range. The patient came for a second comprehensive biochemical screening at 17 – 18 weeks gestation. The results showed the low genetic risk of congenital anomalies. Fetal morphology of the fetus was normal. S.K. came again for consultation at 22 weeks gestation in connection with the admittance of her first 3-year-old child to the hospital because of pneumonia. Serological tests of the child had shown elevated CMV titer - specific IgM. Then we made new serological tests of the patient and the results have shown that the patient was most likely infected by CMV primarily in the first trimester of pregnancy. After consulting about the risk of transmission of CMV to the fetus, the woman chose monthly ultrasound scans and refused amniocentesis. At 36 weeks gestation, in addition to the microcephaly already established, enlargement of the IV brain ventricle at the expense of underdevelopment of the cerebellum was noticed. Also, 2nd to 3rd stage of placenta maturity and low quantity of amniotic fluid was established. A male fetus of weight 2,890 g and height 50 cm was delivered. The fetus was with skin petechiae and hepatosplenomegaly. Neurological examination showed no abnormalities. CONCLUSIONS: In the described case the time interval between infection and ultrasonic manifestations is more than 17 weeks. The long interval between infection and occurrence of ultrasound markers

  11. Hepatitis por citomegalovirus. Importancia del momento de contagio Cytomegalovirus induced hepatitis. Importance of when the infection is acquired

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    R. Torres Peral

    2013-01-01

    Full Text Available Introducción. El citomegalovirus (CMV es la causa más frecuente de infección congénita en nuestro medio, así como de morbimortalidad perinatal.  Caso clínico.Lactante de 55 días que ingresa por ictericia de una semana de evolución, sin acolia ni coluria. Sin procesos infecciosos intercurrentes. Como antecedentes, procede de un embarazo gemelar de 36 semanas con bajo peso al nacimiento. A la exploración destaca coloración pálido-ictérica de piel, con esplenomegalia de 3-5 cm, de consistencia media, sin hepatomegalia. En las pruebas complementarias se objetiva una hepatitis colestásica con serologías positivas para citomegalovirus (IgM. Tras descartar la atresia de vías biliares y confirmar la etiología infecciosa, mediante PCR en plasma y orina, se inicia tratamiento con Ganciclovir intravenoso. Se recupera sangre desecada de las pruebas metabólicas para identificar el origen congénito o adquirido de la infección. Ante la buena evolución de la paciente y la negatividad de la PCR en sangre desecada, se retira el tratamiento 6 semanas después del inicio. Como efecto secundario a la medicación, se objetiva leucopenia leve que responde adecuadamente al tratamiento. Conclusiones.Ante una infección por citomegalovirus, es fundamental identificar el momento de contagio, de cara a establecer el pronóstico a largo plazo. Se sabe que el mayor riesgo de secuelas se asocia con las infecciones congénitas, siendo las que afectan al neurodesarrollo las más frecuentes. A pesar de demostrar el origen infeccioso de la clínica de nuestra paciente, se debe descartar la atresia de vías biliares, dadas las asociaciones existentes entre esta entidad y las infecciones virales. Introduction. Cytomegalovirus (CMV is the most common cause of congenital infection in our media, being responsible of a high rate of perinatal morbility and mortality as well. Case report. A fifty-five day old child presented to the hospital with a jaundice noted

  12. Radiologic findings of an AIDS patient with gastrointestinal mixed infection of cytomegalovirus and Candida

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Isamu; Nakajima, Tetsuji.

    1988-08-01

    A radiologic examination was performed on a 50-year-old homosexual man with AIDS in his gastrointestinal tract. Main abnormalities were ulcerative lesions due to mixed infection of cytomegarovirus and Candida. Esophageal involvement was demonstrated as multiple granulations and ulcers ; gastric involvement, as two ulcers ; and intestinal involvement, as only rapid transit of barium. With the lapse of time, esophageal lesions almost disappeared ; while gastric ulcers remained the same and intestinal involvement was exacerbated. The ulcerations of terminal ileum and colon due to severe bleeding and perforation caused the death.

  13. Intestinal cryptosporidiosis. association with Pneumocystis carinii, cytomegalovirus and Candida sp. Infections

    Directory of Open Access Journals (Sweden)

    K. I. R. Coelho

    1987-10-01

    Full Text Available This is a case report of intestinal cryptosporidiosis diagnosed in histological specimen collected from autopsy. The patient was a child of 5 months admitted to the hospital with severe acute diarrhea associated with Pneumocystis carinii pneumonia, cytomegalic sialadenitis, oral and dermal candidiasis. The presence of multiple opportunistic infections in this case indicated immunodeficiency state. Cryptosporidium sp is a possible etiology of acute diarrhea in both immunodeficient and immunocompetent patients and has to be searched for at autopsy when diagnosis was not possible "in vivo".

  14. Radiologic findings of an AIDS patient with gastrointestinal mixed infection of cytomegalovirus and Candida

    International Nuclear Information System (INIS)

    A radiologic examination was performed on a 50-year-old homosexual man with AIDS in his gastrointestinal tract. Main abnormalities were ulcerative lesions due to mixed infection of cytomegarovirus and Candida. Esophageal involvement was demonstrated as multiple granulations and ulcers ; gastric involvement, as two ulcers ; and intestinal involvement, as only rapid transit of barium. With the lapse of time, esophageal lesions almost disappeared ; while gastric ulcers remained the same and intestinal involvement was exacerbated. The ulcerations of terminal ileum and colon due to severe bleeding and perforation caused the death. (author)

  15. Cytomegalovirus and inflammatory bowel disease.

    OpenAIRE

    Morton, R

    1985-01-01

    An 80 year old man was admitted to hospital with a 4 month history of diarrhoea with blood and mucus. The diarrhoea could not be controlled by a variety of drugs and he died 7 weeks later. Rectal biopsy showed both intranuclear and intracytoplasmic inclusional bodies consistent with cytomegalovirus infection.

  16. Cytomegalovirus and chronic allograft rejection in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Liang-Hui Gao; Shu-Sen Zheng

    2004-01-01

    Cytomegalovirus (CMV) remains one of the most frequent viral infections and the most common cause of death after liver transplantation (LT). Chronic allograft liver rejection remains the major obstacle to long-term allograft survival and CMV infection is one of the suggested risk factors for chronic allograft rejection. The precise relationship between cytomegalovirus and chronic rejection remains uncertain.This review addresses the morbidity of cytomegalovirus infection and the risk factors associated with it, the relationship between cytomegalovirus and chronic allograft liver rejection and the potential mechanisms of it.

  17. Antenatal interventions for preventing the transmission of cytomegalovirus (CMV) from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant.

    LENUS (Irish Health Repository)

    McCarthy, Fergus P

    2012-01-31

    BACKGROUND: Cytomegalovirus (CMV) is a herpesvirus and the most common cause of congenital infection in developed countries. Congenital CMV infection can have devastating consequences to the fetus. The high incidence and the serious morbidity associated with congenital CMV infection emphasise the need for effective interventions to prevent the antenatal transmission of CMV infection. OBJECTIVES: The aim of this review was to assess the benefits and harms of interventions used during pregnancy to prevent mother to fetus transmission of CMV infection. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group\\'s Trials Register (31 December 2010). SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi RCTs investigating antenatal interventions for preventing the transmission of CMV from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. MAIN RESULTS: We identified six studies from the search. None of these studies met the pre-defined criteria for inclusion in this review. AUTHORS\\' CONCLUSIONS: To date, no RCTs are available that examine antenatal interventions for preventing the transmission of CMV from the infected mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. Further research is needed to assess the efficacy of interventions aimed at preventing the transmission of CMV from the mother to fetus during pregnancy including a long-term follow-up of exposed infants and a cost effective analysis.

  18. Specific and Non-Specific Factors of Humoral Immunity as Markers for Pregnancy Loss in Women with Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Irina A. Andrievskaya

    2015-12-01

    Full Text Available The aim of this study was to estimate the changes in humoral immunity and their association with complications of pregnancy (spontaneous abortions, threatened miscarriage, premature birth depending on the gestational age and recurrence of cytomegalovirus infection (CMVI. A direct relationship between the frequency of detection of an anti-CMV IgG antibody titer of 1:1600 and the prevalence of acute respiratory disease during pregnancy has been identified. We found an imbalance in the production of the non-specific antibodies (an increase in the blood levels of total IgM and a decrease in IgA and IgG levels in the subgroup of women with relapsed CMVI at 6 to 8 weeks of gestation and spontaneous abortion, as well as in the subgroup of women with relapsed CMVI at 15 to 21 weeks of gestation and the risk of the late miscarriage, compared to those with relapsed CMVI at 9 to 14 weeks and 22 to 32 weeks of gestation. An increase in blood levels of total IgM and IgG and a decrease in IgA level was identified in the subgroup of women with relapsed CMVI at 9 to14 weeks of gestation and a threatened abortion, as well as in the subgroup of women with relapsed CMVI at 22 to 32 weeks of gestation and preterm birth. The obtained data of the imbalance in the primary and secondary immune response in CMV- seropositive pregnant women during relapsed CMVI indicate disturbances in the systemic and local intercellular interactions of immunocompetent cells, which lead to an imbalance in the production of antibodies involved in the elimination of viral agents and to the development of a systemic inflammatory response that complicates the course of pregnancy. CMVI relapse at 7 to 8 weeks of gestation is associated with reproductive losses; a risk for threatened miscarriage, threatened premature labor, and retrochorial hematoma increases significantly with CMVI relapse in the more remote gestational age.

  19. MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENES

    Directory of Open Access Journals (Sweden)

    T. M. Sokolova

    2007-01-01

    Full Text Available Abstract. Cytomegalovirus (CMV infection in diploid human fibroblasts (HF and levels of cell resistance to this virus were shown to be in direct correlation with high α-interferon (IFNα gene activity and induction of IFNγ gene transcription. Regulation of IFNα mRNA transcription was revealed to be positively associated with cellular DNA synthesis. At the same time, activities of IFNβ and IFNγ genes were at the constantly low level and were not induced in DNA-synthetic phase (S-phase of the cells. Levels of IFNα mRNA synthesis are quite different for G0- vs S-phase-synchronized HF110044 cell cultures: appropriate values for dividing cells (S-phase proved to be 100-fold higher than in resting state (G0. The mode of CMV infection in resting HF-cell could be considered either as acute, or a productive one. On the contrary, proliferating cells exhibited lagging viral syntheses and delayed cell death. Arrest of CMV replication may be, to some extent, comparable with latent infectious state, being associated with high production of IFNα. Both basal and induced levels of IFNα mRNA in CMV-resistant adult human skin fibroblast cells (HSF-1608 were 10-fold higher than in human embryo lung cell line (HELF-977, which is highly sensitive to CMV. Moreover, a short-time induction of IFNγ genes was observed in resistant cells, whereas no such effect was noticed in highly sensitive cells. CMV reproduction in sensitive cell lines (HELF-977 and HELF-110044 partially inhibits IFNα mRNA transcription at the later stages of infection (24 to 48 hours. Thus, cellular resistance and control of CMV infection in diploid fibroblasts are associated predominantly with high transcription of IFNα gene, and with temporal induction of IFNγ gene. We did not reveal any participation of IFNβ genes in protection of human diploid fibroblasts from CMV.

  20. Bone-marrow-derived mesenchymal stem cells as a target for cytomegalovirus infection: Implications for hematopoiesis, self-renewal and differentiation potential

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSCs) in bone marrow (BM) regulate the differentiation and proliferation of adjacent hematopoietic precursor cells and contribute to the regeneration of mesenchymal tissues, including bone, cartilage, fat and connective tissue. BM is an important site for the pathogenesis of human cytomegalovirus (HCMV) where the virus establishes latency in hematopoietic progenitors and can transmit after reactivation to neighboring cells. Here we demonstrate that BM-MSCs are permissive to productive HCMV infection, and that HCMV alters the function of MSCs: (i) by changing the repertoire of cell surface molecules in BM-MSCs, HCMV modifies the pattern of interaction between BM-MSCs and hematopoietic cells; (ii) HCMV infection of BM-MSCs undergoing adipogenic or osteogenic differentiation impaired the process of differentiation. Our results suggest that by altering BM-MSC biology, HCMV may contribute to the development of various diseases

  1. Evaluation of an in-house specific immunoglobulin G (IgG avidity ELISA for distinguishing recent primary from long-term human cytomegalovirus (HCMV infection

    Directory of Open Access Journals (Sweden)

    Souza Silmara de

    2003-01-01

    Full Text Available This article describes the standardization and evaluation of an in-house specific IgG avidity ELISA for distinguishing recent primary from long-term human cytomegalovirus (HCMV infection. The test was standardized with the commercial kit ETI-CYTOK G Plus (Sorin Biomedica, Italy using 8 M urea in phosphate-buffered saline to dissociate low-avidity antibodies after the antigen-antibody interaction. The performance of the in-house assay was compared to that of the commercial automated VIDAS CMV IgG avidity test (bioMérieux, France. Forty-nine sera, 24 from patients with a recent primary HCMV infection and 25 from patients with a long-term HCMV infection and a sustained persistence of specific IgM antibodies, were tested. Similar results were obtained with the two avidity methods. All 24 sera from patients with recently acquired infection had avidity indices compatible with acute HCMV infection by the VIDAS method, whereas with the in-house method, one serum sample had an equivocal result. In the 25 sera from patients with long-term infection, identical results were obtained with the two methods, with only one serum sample having an incompatible value. These findings suggest that our in-house avidity test could be a potentially useful tool for the immunodiagnosis of HCMV infection.

  2. Cytomegalovirus infection masquerading as an ulcerative colitis flare-up: case report and review of the literature.

    OpenAIRE

    Begos, D. G.; Rappaport, R; Jain, D.

    1996-01-01

    We report the case of a patient with a case of cytomegalovirus (CMV) colitis, which presented as a flare-up of her ulcerative colitis. Standard treatment for the flare-up, which included intravenous corticosteroids, bowel rest, topical salicylates and ultimately colectomy were not effective. The patient did not improve until therapy with intravenous ganciclovir was initiated. There have been 26 previous reports of CMV colitis complicating inflammatory bowel disease (IBD). The diagnosis is not...

  3. Central pontine myelinolysis secondary to cytomegalovirus hepatitis in a 10-month-old child

    Energy Technology Data Exchange (ETDEWEB)

    Tarhan, Cagla N.; Firat, Ali; Agildere, Muhtesem A. [Fevzi Cakmak Cad. 10. Sok. No:45, 06490 Bahcelievler, Ankara (Turkey); Otken, Arzu; Demirceken, Fulya [Sami Ulus Children' s Hospital, Department of Paediatrics, Ankara (Turkey)

    2003-01-01

    We present a 10-month-old child with central pontine myelinolysis (CPM) secondary to chronic active hepatitis due to cytomegalovirus (CMV) infection. A total of 35 paediatric cases of pontine and/or extrapontine myelinolysis are reported and, to our knowledge, CPM secondary to CMV hepatitis in an infant has not been previously reported. The MRI findings are highlighted. (orig.)

  4. Central pontine myelinolysis secondary to cytomegalovirus hepatitis in a 10-month-old child

    International Nuclear Information System (INIS)

    We present a 10-month-old child with central pontine myelinolysis (CPM) secondary to chronic active hepatitis due to cytomegalovirus (CMV) infection. A total of 35 paediatric cases of pontine and/or extrapontine myelinolysis are reported and, to our knowledge, CPM secondary to CMV hepatitis in an infant has not been previously reported. The MRI findings are highlighted. (orig.)

  5. Cytomegalovirus hepatitis and myopericarditis

    Institute of Scientific and Technical Information of China (English)

    Leire Zubiaurre; Eva Zapata; Luis Bujanda; María Castillo; Igor Oyarzabal; Maria A Gutiérrez-Stampa; Angel Cosme

    2007-01-01

    Cytomegalovirus (CMV) infection in inmunocompetent hosts generally is asymptomatic or may present as a mononucleosis syndrome but rarely can lead to severe organ complications. We report a case of simultaneous hepatic and pericardic CMV infection in a 36-year old immunocompetent man. He was admitted to coronary unit with fever, chest pain radiated to shoulders,changes on electrocardiogram with diffuse ST elevation and modest laboratory elevations in the MB fraction of creatine kinase (CK-MB) of 33.77 μg/L (0.1-6.73), serum cardiac troponin T of 0.904 ng/mL (0-0.4), creatine kinase of 454 U/L (20-195) and myoglobin of 480.4 μg/L (28-72). Routine laboratory test detected an elevation of aminotransferase level: alanine aminotransferase 1445 U/L, aspartate aminotransferase 601 U/L. We ruled out other causes of hepatitis with normal results except IgM CMV. The patient was diagnosed with myopericarditis and hepatitis caused by cytomegalovirus and started symptomatic treatment with salicylic acid. In few days the laboratory findings became normal and the patient was discharged.

  6. Human Cytomegalovirus UL97 Kinase Activity Is Required for the Hyperphosphorylation of Retinoblastoma Protein and Inhibits the Formation of Nuclear Aggresomes

    Energy Technology Data Exchange (ETDEWEB)

    Prichard, Mark N.; Sztul, Elizabeth; Daily, Shannon L.; Perry, Amie L.; Frederick, Samuel L.; Gill, Rachel B.; Hartline, Caroll B.; Streblow, Daniel N.; Varnum, Susan M.; Smith, Richard D.; Kern, Earl R.

    2008-05-01

    Cells infected with human cytomegalovirus in the absence of UL97 kinase activity produce large nuclear aggregates that sequester considerable quantities of viral proteins. A transient expression assay suggested that pp71 and IE1 were also involved in this process, and this suggestion was significant, since both proteins have been reported to interact with components of promyelocytic leukemia (PML) bodies (ND10) and also interact functionally with retinoblastoma pocket proteins (RB). PML bodies have been linked to the formation of nuclear aggresomes, and colocalization studies suggested that viral proteins were recruited to these structures and that UL97 kinase activity inhibited their formation. Proteins associated with PML bodies were examined by Western blot analysis, and pUL97 appeared to specifically affect the phosphorylation of RB in a kinasedependent manner. Three consensus RB binding motifs were identified in the UL97 kinase, and recombinant viruses were constructed in which each was mutated to assess a potential role in the phosphorylation of RB and the inhibition of nuclear aggresome formation. The mutation of either the conserved LxCxE RB binding moti for the lysine required for kinase activity impaired the ability of the virus to stabilize and phosphorylate RB. We concluded from these studies that both UL97 kinase activity and the LxCxE RB binding motif are required for the phosphorylation and stabilization of RB in infected cells and that this effect can be antagonized by the antiviral drug maribavir. These data also suggest a potential link between RB function and the formation of aggresomes.

  7. Detection of cytomegalovirus in urine of HIV-infected patients by DNA-DNA hybridization comparison with virus isolation, immunofluorescence and immunoperoxidase

    Directory of Open Access Journals (Sweden)

    Angel Valdivia

    1992-03-01

    Full Text Available Immunofluorescence and immunoperoxidase test directed against early viral antigens, and DNA-DNA hybridization were compared with viral isolation for their abilities to detect Cytomegalovirus (CVM in the urine of 89 HIV infected patients. From the 100 urine samples collected, 70 were found positive by at least one method. Considering viral isolation as the "gold standard" technique, immunofluorescence and immunoperoxidase had a sensitivity of 92.3% and88% respectively, with a specificity in both cases of 95%. DNA-DNA hybridization showed a sensitivity of 90% but with lower (60% specificity. All of the three assays were effective in detecting CVM from urine and the technical advantage of each is discussed.

  8. Outcome of surgery in post-cytomegalovirus retinal detachment: Experience before and in the era of highly active anti-retroviral therapy in Indian eyes

    Directory of Open Access Journals (Sweden)

    Ramandeep Singh

    2013-01-01

    Full Text Available Purpose: To evaluate the outcome of surgery for cytomegalovirus associated retinal detachment (CMVRD in human immunodeficiency virus (HIV-infected patients in pre-highly active antiretroviral therapy (HAART and HAART era in Indian eyes. Materials and Methods: Retrospective, we reviewed medical records of all consecutive HIV patients, who underwent surgical repair for CMVRD from July 1998 to June 2011. We divided patients into two groups, i.e. group 1, pre HAART era and group 2, HAART era. We compared two groups for various parameters like visual outcome, surgical success, additional procedures, follow-up, etc., Results: Twenty-eight eyes of 26 patients were included; 12 eyes of the 11 patients in group 1 and 16 eyes of the 15 patients in group 2. Significant visual acuity improvement was seen in both groups. Complete anatomic success was seen in 11 eyes in group 1 and 15 eyes in group 2. One additional procedure in group 1 and 29 additional procedures were done in group 2. A mean follow-up was 16 months in group 1 and 41 months in group 2. Conclusion: There was no difference in outcome in pre-HAART and HAART group, except for longer follow-up and additional surgical procedures in HAART group.

  9. Resistance to maribavir is associated with the exclusion of pUL27 from nucleoli during human cytomegalovirus infection

    OpenAIRE

    Hakki, Morgan; Drummond, Coyne; Houser, Benjamin; Marousek, Gail; Chou, Sunwen

    2011-01-01

    Select mutations in the human cytomegalovirus (HCMV) gene UL27 confer low-grade resistance to the HCMV UL97 kinase inhibitor maribavir (MBV). It has been reported that the 608-amino acid UL27 gene product (pUL27) normally localizes to cell nuclei and nucleoli, whereas its truncation at codon 415, as found in a MBV-resistant mutant, results in cytoplasmic localization. We now show that in the context of full-length pUL27, diverse single amino acid substitutions associated with MBV resistance r...

  10. Fetal infection from rubeovirus or cytomegalovirus: correlation among maternal serological profiles, invasive diagnostic procedures, and long-term follow-up.

    Science.gov (United States)

    Noia, G; Masini, L; De Santis, M; Scavo, M; Pomini, F; Grillo, R; Cattani, P; Ranno, O; Caruso, A; Mancuso, S

    1998-01-01

    Different variables influence the possibility that maternal viral infection may be transmitted to the fetus, although not all fetal infections result in fetal "illness" with consequent fetopathy. As concerns the fetus, prenatal diagnosis includes invasive techniques necessary for fetal tissue sampling. These techniques carry some risks. The fetal infectious risk, as determined by maternal clinico-serological profile and according to sonographic investigation, always should be weighed against the risks and benefits of invasive diagnostic procedures. The present study re-elaborates the criteria necessary for defining fetal risk as related to the maternal serological profile. In the 26 mothers with rubeola infection, the incidence of fetal mortality was 7.7%. Fetal prognosis worsens with the precocity of eruption. In these cases the esantema is the most reliable prognostic element as an indication to perform the invasive procedure. In the 15 patients with cytomegalovirus infection, no fetal or postnatal losses occurred. Morbidity occurred in 13.3% of cases, and the two ill fetuses were classified in the same risk group. In this group of patients, the maternal serological profile is a significant predictor of fetal morbidity. PMID:9502669

  11. Infección por Citomegalovarius con compromiso hepático en adultos inmunocompetentes Cytomegalovirus infection with hepatic involvement in immunocompetent adults

    Directory of Open Access Journals (Sweden)

    Claudia Vujacich

    2006-06-01

    presented fever and asthenia, mild to moderate increase of transaminases and serological findings compatible with recent cytomegalovirus infection. We excluded patients with a history of transfusions, drug abuse, immunodeficiencies, preexistent hepatic impairment or serological findings compatible with acute hepatitis A, B and C (HAV, HBV, HCV and Epstein Barr virus (EBV. The laboratory diagnosis of recent cytomegalovirus infection was made by especific IgM detection (ELISA or a significant increase of specific IgG. The most frequent symptoms were fever (85% and asthenia (83%, followed by cephalea (25%, splenomegaly (20%, adenomegalies (22%, pharyngitis (25%, myalgias (25% and hepatomegaly (19%. All the patients showed moderate increase of transaminases and lymphomonocytosis (73/73. In average, ALT was increased by 6 fold and AST by 3.5 fold. The clinical characteristics that differentiate CMV infection from Epstein-Barr infection are the lesser frequency of adenomegalies and pharyngitis in the former. The differential diagnosis of CMV infection with hepatic involvement from acute hepatitis A and B, is based on the absence of jaundice, the lower elevation of transaminases, the intense lymphomonocytosis and the presence of specific IgM against CMV that are characteristic of CMV infection. In conclusion, in previously healthy young adults with fever, intense asthenia, lymphomonocytosis and moderate increase in transaminases levels, cytomegalovirus infection should be investigated.

  12. Postmortem diagnosis of cytomegalovirus and accompanying other infection agents by real-time PCR in cases of sudden unexpected death in infancy (SUDI).

    Science.gov (United States)

    Yagmur, Gulhan; Ziyade, Nihan; Elgormus, Neval; Das, Taner; Sahin, M Feyzi; Yildirim, Muzaffer; Ozgun, Ayse; Akcay, Arzu; Karayel, Ferah; Koc, Sermet

    2016-02-01

    As an opportunistic pathogen with high mortality rates, Cytomegalovirus (CMV) may lead to fatal disseminated CMV infection of the premature and newborn; thus necessitating the demonstration of CMV-DNA with clinical history and/or histopathological findings of CMV infection and defining other bacterial and viral infection agents with real-time polymerase chain reaction (RT-PCR) in udden unexpected death in infancy (SUDI) cases as we aimed in this study. 314 (144 female, 170 male) SUDI cases were prospectively investigated from January 2013 to January 2015 in Istanbul Forensic Medicine Institution. The study includes 87 tissue samples of 39 cases for post-mortem histopathological examination of interstitial pneumonia, myocarditis, meningitis, encephalitis, hepatitis, colitis or tubulointerstitial nephritis and/or accompanying chronic sialadenitis. CMV-DNA was found positive in 35 (40.2%) salivary gland, 19 (21.8%) lung, 1 (1.1%) tonsil, and 1 (1.1%) brain tissues. CMV sialadenitis and/or CMV pneumonia associated with other viral and/or bacterial agents were detected in 23 (60%) of 39 infant cases. The demonstration of CMV-DNA would significantly clarify the cause of death and collection of epidemiological data in SUDI cases with clinical history and histopathological findings of CMV infection accompanying chronic CMV sialadenitis. Furthermore, CMV suppresses the immune system, and may predispose to other bacterial and/or viral infections in these cases. Post-mortem molecular investigations are useful in explaining cause of death in SUDI with a suspicion of infection in forensic autopsies.

  13. Properties of virion transactivator proteins encoded by primate cytomegaloviruses

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    Barry Peter A

    2009-05-01

    UL82 homologs stimulated the early release of ATRX from nuclear domain 10. Conclusion All of the UL82 homolog proteins analysed activated gene expression, but surprising differences in other aspects of their properties were revealed. The results provide new information on early events in infection with cytomegaloviruses.

  14. Incidence of human herpes virus-6 and human cytomegalovirus infections in donated bone marrow and umbilical cord blood hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Behzad-Behbahani A

    2008-01-01

    Full Text Available This study examined the incidence of human herpes virus-6 (HHV-6 and human cytomegalovirus (HCMV infections that are potentially transmitted to haematopoietic stem cells (HSC transplant recipients via bone marrow (BM or umbilical cord blood (UCB. Bone marrow progenitor cells were collected from 30 allogenic BM donors. UCB HSC were collected from 34 subjects. The extracted DNA was then processed using nested polymerase chain reaction (nPCR technique. HCMV and HHV-6 serological status were determined by enzyme immunoassay (EIA. Nested PCR identified HCMV in 22 (73% of 30 samples of BM progenitor cells but in only eight (23.5% of 34 samples of UBC HSC ( P = 0.001. HHV-6 DNA was detected in 11 (36.6% of 30 BM progenitor cells and in only one (2.9% of 34 UBC cells ( P = 0.002. Both HHV-6 and HCMV infections were determined in nine (26.5% of 34 bone marrow samples. The results indicate that, the risk of HCMV and HHV-6 via BM progenitor cells is higher than transmission by UCB cells ( P= 0.04.

  15. Enhanced expression of full-length human cytomegalovirus fusion protein in non-swelling baculovirus-infected cells with a minimal fed-batch strategy.

    Directory of Open Access Journals (Sweden)

    Marco Patrone

    Full Text Available Human cytomegalovirus congenital infection represents an unmet medical issue and attempts are ongoing to develop an effective vaccine. The virion fusion players of this enveloped virus are the natural targets to achieve this goal and to develop novel anti-viral therapies. The secreted ectodomain of the viral fusion factor glycoprotein B (gB has been exploited so far as an alternative to the cumbersome expression of the wild type trans-membrane protein. In the soluble form, gB showed encouraging but limited potential as antigen candidate calling for further efforts. Here, the exhaustive evaluation of the Baculovirus/insect cell expression system has been coupled to an orthogonal screening for expression additives to produce full-length gB. In detail, rapamycin was found to prolong gB intracellular accumulation while inhibiting the infection-induced cell swelling. Not obvious to predict, this inhibition did not affect Baculovirus growth, revealing that the virus-induced cell size increase is a dispensable side phenotype. In parallel, a feeding strategy for the limiting nutrient cysteine has been set up which improved gB stability. This multi-modal scheme allowed the production of full-length, mutation-free gB in the milligram scale. The recombinant full-length gB obtained was embedded into a stable mono-dispersed particle substantially larger than the protein trimer itself, according to the reported association of this protein with detergent-resistant lipid domains.

  16. Toxoplasmosis, Parvovirus, and Cytomegalovirus in Pregnancy.

    Science.gov (United States)

    Feldman, Deborah M; Keller, Rebecca; Borgida, Adam F

    2016-06-01

    There are several infections in adults that warrant special consideration in pregnant women given the potential fetal consequences. Among these are toxoplasmosis, parvovirus B19, and cytomegalovirus. These infections have an important impact on the developing fetus, depending on the timing of infection. This article reviews the modes of transmission as well as maternal and neonatal effects of each of these infections. In addition, the article outlines recommended testing, fetal surveillance, and treatment where indicated. PMID:27235921

  17. The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV Infected Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Melpomeni Tseliou

    2016-01-01

    Full Text Available Background/Aims: Rho GTPases are crucial regulators of the actin cytoskeleton, membrane trafficking and cell signaling and their importance in cell migration and invasion is well- established. The human cytomegalovirus (HCMV is a widespread pathogen responsible for generally asymptomatic and persistent infections in healthy people. Recent evidence indicates that HCMV gene products are expressed in over 90% of malignant type glioblastomas (GBM. In addition, the HCMV Immediate Early-1 protein (IE1 is expressed in >90% of tumors analyzed. Methods: RhoA, RhoB and RhoC were individually depleted in U373MG glioblastoma cells as well as U373MG cells stably expressing the HCMV IE1 protein (named U373MG-IE1 cells shRNA lentivirus vectors. Cell proliferation assays, migration as well as wound-healing assays were performed in uninfected and HCMV-infected cells. Results: The depletion of RhoA, RhoB and RhoC protein resulted in significant alterations in the morphology of the uninfected cells, which were further enhanced by the cytopathic effect caused by HCMV. Furthermore, in the absence or presence of HCMV, the knockdown of RhoB and RhoC proteins decreased the proliferation rate of the parental and the IE1-expressing glioblastoma cells, whereas the knockdown of RhoA protein in the HCMV infected cell lines restored their proliferation rate. In addition, wound healing assays in U373MG cells revealed that depletion of RhoA, RhoB and RhoC differentially reduced their migration rate, even in the presence or the absence of HCMV. Conclusion: Collectively, these data show for the first time a differential implication of Rho GTPases in morphology, proliferation rate and motility of human glioblastoma cells during HCMV infection, further supporting an oncomodulatory role of HCMV depending on the Rho isoforms' state.

  18. PUL21a-Cyclin A2 interaction is required to protect human cytomegalovirus-infected cells from the deleterious consequences of mitotic entry.

    Directory of Open Access Journals (Sweden)

    Martin Eifler

    2014-10-01

    Full Text Available Entry into mitosis is accompanied by dramatic changes in cellular architecture, metabolism and gene expression. Many viruses have evolved cell cycle arrest strategies to prevent mitotic entry, presumably to ensure sustained, uninterrupted viral replication. Here we show for human cytomegalovirus (HCMV what happens if the viral cell cycle arrest mechanism is disabled and cells engaged in viral replication enter into unscheduled mitosis. We made use of an HCMV mutant that, due to a defective Cyclin A2 binding motif in its UL21a gene product (pUL21a, has lost its ability to down-regulate Cyclin A2 and, therefore, to arrest cells at the G1/S transition. Cyclin A2 up-regulation in infected cells not only triggered the onset of cellular DNA synthesis, but also promoted the accumulation and nuclear translocation of Cyclin B1-CDK1, premature chromatin condensation and mitotic entry. The infected cells were able to enter metaphase as shown by nuclear lamina disassembly and, often irregular, metaphase spindle formation. However, anaphase onset was blocked by the still intact anaphase promoting complex/cyclosome (APC/C inhibitory function of pUL21a. Remarkably, the essential viral IE2, but not the related chromosome-associated IE1 protein, disappeared upon mitotic entry, suggesting an inherent instability of IE2 under mitotic conditions. Viral DNA synthesis was impaired in mitosis, as demonstrated by the abnormal morphology and strongly reduced BrdU incorporation rates of viral replication compartments. The prolonged metaphase arrest in infected cells coincided with precocious sister chromatid separation and progressive fragmentation of the chromosomal material. We conclude that the Cyclin A2-binding function of pUL21a contributes to the maintenance of a cell cycle state conducive for the completion of the HCMV replication cycle. Unscheduled mitotic entry during the course of the HCMV replication has fatal consequences, leading to abortive infection and

  19. An artemisinin-derived dimer has highly potent anti-cytomegalovirus (CMV and anti-cancer activities.

    Directory of Open Access Journals (Sweden)

    Ran He

    Full Text Available We recently reported that two artemisinin-derived dimers (dimer primary alcohol 606 and dimer sulfone 4-carbamate 832-4 are significantly more potent in inhibiting human cytomegalovirus (CMV replication than artemisinin-derived monomers. In our continued evaluation of the activities of artemisinins in CMV inhibition, twelve artemisinin-derived dimers and five artemisinin-derived monomers were used. Dimers as a group were found to be potent inhibitors of CMV replication. Comparison of CMV inhibition and the slope parameter of dimers and monomers suggest that dimers are distinct in their anti-CMV activities. A deoxy dimer (574, lacking the endoperoxide bridge, did not have any effect on CMV replication, suggesting a role for the endoperoxide bridge in CMV inhibition. Differences in anti-CMV activity were observed among three structural analogs of dimer sulfone 4-carbamate 832-4 indicating that the exact placement and oxidation state of the sulfur atom may contribute to its anti-CMV activity. Of all tested dimers, artemisinin-derived diphenyl phosphate dimer 838 proved to be the most potent inhibitor of CMV replication, with a selectivity index of approximately 1500, compared to our previously reported dimer sulfone 4-carbamate 832-4 with a selectivity index of about 900. Diphenyl phosphate dimer 838 was highly active against a Ganciclovir-resistant CMV strain and was also the most active dimer in inhibition of cancer cell growth. Thus, diphenyl phosphate dimer 838 may represent a lead for development of a highly potent and safe anti-CMV compound.

  20. 秦巴山区孕妇巨细胞病毒活动性感染与血清锌水平的关系%The relationship between cytomegalovirus actively infection and the level of serum zinc in pregnant women of the area Qinba with high incidence of mental retardation

    Institute of Scientific and Technical Information of China (English)

    李芬; 曹懿; 韩蓁; 王亚文; 李学成; 任永惠

    2005-01-01

    目的探讨秦巴山区孕妇巨细胞病毒(human cytomegalovirus,HCMV)活动性感染与血清锌含量的关系.方法采用ELISA和PCR相结合的方法检测秦巴山区HCMV活动性感染的妊娠妇女52例作为病例组,同期检测的52例未感染孕妇作为对照组,用原子吸收光谱法测定两组孕妇血清锌含量,随访妊娠结局并检测其分娩的新生儿尿液中的HCMV-DNA.结果①新生儿尿液HCMV-DNA阳性者共21例,宫内传播率40.38%(21/52).②HCMV活动性感染孕妇血清锌平均值为46.29±13.81μg/dl明显低于未感染孕妇组82.73±23.98μg/dl(P<0.05).结论该地区HCMV活动性感染孕妇体内明显缺锌,可能与该地区智力低下(MR)发病率高有一定关系.

  1. Diagnosis of cytomegalovirus infections by qualitative and quantitative PCR in HIV infected patients Diagnóstico de infecção por CMV em pacientes infectados pelo HIV utilizando PCR qualitativa e quantitativa

    Directory of Open Access Journals (Sweden)

    Aldo de Albuquerque CUNHA

    2002-01-01

    Full Text Available A high incidence of cytomegalovirus (CMV infections is observed in Brazil. These viruses are causatives of significant morbidity and mortality among patients with advanced human immunodeficiency virus (HIV infection. This work, shows the application of a PCR on determination of CMV load in the buffy coat and plasma. We analyzed the samples of 247 HIV infected patients in order to diagnose CMV infection and disease. We developed a semi-quantitative PCR that amplifies part of the glycoprotein B (gB gene of CMV. The semi-quantitative PCR was carried out only in positive clinical samples in a qualitative PCR confirmed by a nested-PCR. CD4 lymphocyte count, HIV viral load and CMV disease symptom were correlated with CMV load. CMV genome was detected in the buffy coat of 82 of 237 (34.6% patients, in 10 of these the CMV load was determined varying between 928 and 332 880 viral copies/mug DNA. None of these 237 patients developed any suggestive manifestation of CMV disease. For the other 10 HIV infected patients selected based on the suspicion of CMV disease, CMV genome was detected in only one case. This patient presented a high CMV load, 8 000 000 copies/mug DNA, and developed a disseminated form of CMV disease including hepatitis and retinitis. Our results were greatly influenced by the impact of the highly active antiretroviral therapy that reduced incidence of CMV viremia and occurrence of CMV disease in the HIV infected patients.Uma alta incidência de infecção pelo citomegalovirus (CMV é observada no Brasil. Este vírus é responsável por significante morbi-mortalidade entre pacientes infectados pelo vírus da imunodeficiência humana (HIV. Neste estudo, mostramos a aplicação de uma PCR quantitativa para determinar a carga de CMV nos leucócitos do sangue periférico e no plasma de 247 pacientes infectados pelo HIV. As amostras clínicas foram previamente testadas por uma PCR qualitativa e confirmadas por uma nested-PCR para posteriormente

  2. Inflammation, Infection, and Future Cardiovascular Risk

    Science.gov (United States)

    2016-03-15

    Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Myocardial Infarction; Venous Thromboembolism; Heart Diseases; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Herpesviridae Infections; Inflammation

  3. Are female daycare workers at greater risk of cytomegalovirus infection? A secondary data analysis of CMV seroprevalence between 2010 and 2013 in Hamburg, Germany

    Directory of Open Access Journals (Sweden)

    Stranzinger, Johanna

    2016-04-01

    Full Text Available Background: Close contact with asymptomatic children younger than three years is a risk factor for a primary cytomegalovirus (CMV infection. In pregnant women, such primary infection increases the risk of CMV-induced feto- or embryopathy. Daycare providers have therefore implemented working restrictions for pregnant daycare workers (DCWs in accordance with legislation and guidelines for maternity protection. However, little is known about the infection risk for DCWs. We therefore compared the prevalence of CMV antibodies of pregnant DCWs to that of female blood donors (BDs.Method: In a secondary data analysis, the prevalence of anti-CMV IgG among pregnant DCWs (N=509 in daycare centers (DCCs was compared to the prevalence of female first-time BDs (N=14,358 from the greater region of Hamburg, Germany. Data collection took place between 2010 and 2013. The influence of other risk factors such as age, pregnancies and place of residence was evaluated using logistic regression models. Results: The prevalence of CMV antibodies in pregnant DCWs was higher than in female BDs (54.6 vs 41.5%; OR 1.6; 95%CI 1.3–1.9. The subgroup of BDs who had given birth to at least one child and who lived in the city of Hamburg (N=2,591 had a prevalence of CMV antibodies similar to the prevalence in pregnant DCWs (53.9 vs 54.6%; OR 0.9; 95%CI 0.8–1.2. Age, pregnancy history and living in the center of Hamburg were risk factors for CMV infections.Conclusion: The comparison of pregnant DCWs to the best-matching subgroup of female first-time BDs with past pregnancies and living in the city of Hamburg does not indicate an elevated risk of CMV infection among DCWs. However, as two secondary data sets from convenience samples were used, a more detailed investigation of the risk factors other than place of residence, age and maternity was not possible. Therefore, the CMV infection risk in DCWs should be further studied by taking into consideration the potential preventive

  4. Cytomegalovirus appendicitis in an immunocompetent host.

    Science.gov (United States)

    Canterino, Joseph E; McCormack, Michael; Gurung, Ananta; Passarelli, James; Landry, Marie L; Golden, Marjorie

    2016-05-01

    Cytomegalovirus (CMV) is a common viral pathogen. Asymptomatic infection or a mononucleosis syndrome are the most common manifestations in otherwise healthy individuals. End-organ disease is rare in immunocompetent individuals. Here, we describe a case of CMV appendicitis in a patient without an immune-compromising condition. PMID:26942831

  5. Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant

    Science.gov (United States)

    2015-06-03

    Hematopoietic/Lymphoid Cancer; Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Cytomegalovirus Infection; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma

  6. The survey analysis of the cytomegalovirus infection for 350 newborns%350例新生儿巨细胞病毒感染现状调查与分析

    Institute of Scientific and Technical Information of China (English)

    陈廷瑞; 卢立党; 郭爱红; 李绍锦

    2013-01-01

    目的:探讨新生儿巨细胞病毒(CMV)感染的影响因素并提出预防措施.方法:对350例孕母脐带血巨细胞病毒抗体及新生儿尿巨细胞病毒DNA检测并收集相关信息进行统计学分析.结果:孕母脐带血抗体阳性的新生儿CMV-DNA感染率较高,达21.62% (P<0.01),并且IgM抗体阳性比IgG抗体阳性的更为显著(Fisher概率确切法P<0.05).结论:新生儿CMV-DNA感染存在明显的母婴垂直传播现象,近期感染的孕母传播率更高,应着重加强对孕母孕前的诊断治疗和落实孕期的预防措施.%Objective: To study the influential factors of the newborns human cytomegalovirus infective and put forward the preventive measures. Methods: To screen the cord blood cytomegalovirus antibodies of 350 pregnancies and the neonatal urine cytomegalovirus DNA, then the related information was collected and analyzed by the statistical methods. Results: The CMV - DNA infective rates (21. 62% ) of the newborns whose mothers had a positive cord blood antibody were higher, and the positive of IgM antibody was more marked than the single positive of IgG antibody ( P <0. 05) . Conclusion: The neonatal CMV - DNA infection has a obvious vertical transmission, there is a higher spread rate from the recent infective pregnancies. We should strengthen the pregnant diagnosis and treatment and carry out the pregnancy prevention measures.

  7. Treg/Th17平衡在巨细胞病毒感染发病机制中的作用%Role of Treg/Th17 balance in the pathogenesis of cytomegalovirus infection

    Institute of Scientific and Technical Information of China (English)

    谭艳芳; 于四景; 王婕; 李双杰

    2012-01-01

    目的:研究调节性T细胞(Treg/Th17)细胞失衡在巨细胞病毒感染(CMV)免疫调节机制中的作用.方法:将CMV感染患儿按诊断标准分为激活感染组与潜伏感染组,同时设立正常对照组,采用流式细胞术(FCM)分析各组外周血Treg、Th17的百分比,并计算Treg/Th17比值;同时采用ELISA和RT-PCR法检测Treg主要相关因子(IL-10、Foxp3)和Th17主要相关因子(TGF-β、IL-17、IL-6、IL-23及ROR-γt)表达水平.结果:与对照组比较,CMV感染后Treg细胞百分率降低,Th17细胞升高,致Treg/Th17比值下降(P<0.05);CMV感染后两组间比较,激活感染组Trg、Th17比值和Treg主要相关因子表达水平下降更明显,而Th17主要相关因子表达水平显著上调,差异均有统计学意义(P<0.05).结论:Treg/Th17平衡参与了CMV感染发病免疫机制,并可能与病毒潜伏-激活状态相关.%AEW: To investigate the role of Treg/Thl7 balance in the immune-regulated mechanism of cytomegalovirus (CMV) infection. METHODS: According to the diagnostic criteria of the CMV infection, the patients with CMV infection were divided into the activate infection group and the latent infection group, and the normal children were recruited as control group. The percents of Treg and Thl7 in peripheral blood were detected by flow cytometry to calculate Treg/Thl7 ratio. ELJSA and RT-PCR were performed to determine the levels of the related factors of Treg (IL-10, Foxp3) and Thl7 (TGF-β, IL-17, IL-6, IL-23, ROR-γt), respectively. RESULTS: Compared with the control group, the proportion of Treg in peripheral blood was reduced, Thl7 increased, so Treg/Thl7 ratio went down after CMV infection (P < 0.05). By comparison between two groups of CMV infection, Treg/Thl7 ratio and Treg related factors of the activate Infection group decreased significantly (P < 0.05), but Thl7 related factors were up-regulated significantly (P<0.05). CONCLUSION: Treg/Thl7 balance takes part in the immune-regulated mechanism

  8. Cytomegalovirus seropositivity is associated with herpes zoster

    OpenAIRE

    Ogunjimi, Benson; Hens, N; Pebody, R; H Jansens; H. Seale; Quinlivan, M.; Theeten, H.; Goossens, Herman; Breuer, Judy; Beutels, Philippe

    2015-01-01

    Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively r...

  9. [Mononucleosis caused by cytomegalovirus].

    Science.gov (United States)

    Lajo Plaza, A; del Castillo Martín, F; Martínez Zapico, R

    1990-01-01

    Sixteen cases of mononucleosis due to cytomegalovirus, are presented. The selection of patients was based on clinical criteria. Symptoms are compared with another series of patients affected with mononucleosis by Epstein-Barr virus. We have not found differences comparing the fever, cervical adenopathies and faringoamigdalitis. Differences were significant in hepatomegaly. We conclude that the clinical picture of cytomegalovirus mononucleosis is very similar to those of the Epstein-Barr mononucleosis.

  10. Immunomodulation by cytomegaloviruses: manipulative strategies beyond evasion.

    Science.gov (United States)

    Mocarski, Edward S

    2002-07-01

    Human cytomegalovirus (CMV) remains the major infectious cause of birth defects as well as an important opportunistic pathogen. Individuals infected with CMV mount a strong immune response that suppresses persistent viral replication and maintains life-long latency. Loss of immune control opens the way to virus reactivation and disease. The large number of immunomodulatory functions encoded by CMV increases the efficiency of infection, dissemination, reactivation and persistent infection in hosts with intact immune systems and could contribute to virulence in immunocompromised hosts. These functions modulate both the innate and adaptive arms of the immune response and appear to target cellular rather than humoral responses preferentially. CMV encodes a diverse arsenal of proteins focused on altering and/or mimicking: (1) classical and non-classical major histocompatibility complex (MHC) protein function; (2) leukocyte migration, activation and cytokine responses; and (3) host cell susceptibility to apoptosis. Evidence that the host evolves mechanisms to counteract virus immune modulation is also accumulating. Although immune evasion is certainly one clear goal of the virus, the pro-inflammatory impact of certain viral functions suggests that increased inflammation benefits viral dissemination. The ability of such viral functions to successfully 'face off' against the host immune system ensures the success of this pathogen in the human population and could provide key insights into disease mechanisms. PMID:12110212

  11. Production of good manufacturing practice-grade cytotoxic T lymphocytes specific for Epstein-Barr virus, cytomegalovirus and adenovirus to prevent or treat viral infections post-allogeneic hematopoietic stem cell transplant.

    Science.gov (United States)

    Sili, Uluhan; Leen, Ann M; Vera, Juan F; Gee, Adrian P; Huls, Helen; Heslop, Helen E; Bollard, Catherine M; Rooney, Cliona M

    2012-01-01

    Infections with a range of common community viruses remain a major cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation. T cells specific for cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenoviruses can safely prevent and infections with these three most common culprits, but the manufacture of individual T cell lines for each virus would be prohibitive in terms of time and cost. We have demonstrated that T cells specific for all three viruses can be manufactured in a single culture using monocytes and EBV-transformed B lymphoblastoid cell lines (LCLs), both transduced with an adenovirus vector expressing pp65 of CMV, as antigen-presenting cells. Trivirus-specific T cell lines produced from healthy stem cell donors could prevent and treat infections with all three viruses, not only in the designated recipient, but in unrelated, partially-HLA-matched third party recipients. We now provide the details and logistics of T cell manufacture.

  12. Placental trophoblasts resist infection by multiple human immunodeficiency virus (HIV) type 1 variants even with cytomegalovirus coinfection but support HIV replication after provirus transfection.

    OpenAIRE

    Kilani, R T; Chang, L J; Garcia-Lloret, M I; Hemmings, D; Winkler-Lowen, B; Guilbert, L J

    1997-01-01

    Whether cell-free human immunodeficiency virus type 1 (HIV-1) can productively infect placental trophoblasts (which in turn could transmit the virus into the fetal circulation) is controversial but essential to know for the evaluation of alternative routes (such as cell-mediated infection or trophoblast damage). We have addressed infection factors such as cell purity, source, culture methods, and activation states as well as virus variant and detection methods to conclusively determine the ou...

  13. Natural killer function following allogeneic bone marrow transplantation. Very early reemergence but strong dependence of cytomegalovirus infection

    DEFF Research Database (Denmark)

    Hokland, M; Jacobsen, N; Ellegaard, J;

    1988-01-01

    Natural killer (NK) cell function was followed sequentially after allogeneic bone marrow transplantation (BMT) using three approaches: (1) chromium-release assay with purified mononuclear effector cells, (2) chromium-release assay with whole blood effectors, and 3) enumeration of lymphocytes......) infections (primary or reactivated). In contrast, the presence of graft-versus-host (GVH) disease did not associate with consistent changes in the NK parameters measured here. After the first month of increase, NK declined reaching levels near those observed in their respective bone marrow donors at day 90...

  14. The Effects of Age and Latent Cytomegalovirus Infection on NK-Cell Phenotype and Exercise Responsiveness in Man

    Directory of Open Access Journals (Sweden)

    Austin B. Bigley

    2015-01-01

    Full Text Available The redeployment of NK-cells in response to an acute bout of exercise is thought to be an integral component of the “fight-or-flight” response, preparing the body for potential injury or infection. We showed previously that CMV seropositivity impairs the redeployment of NK-cells with exercise in the young. In the current study, we examined the effect of aging on the redeployment of NK-cells with exercise in the context of CMV. We show here that CMV blunts the exercise-induced redeployment of NK-cells in both younger (23–39 yrs and older (50–64 yrs subjects with older CMVneg subjects showing the largest postexercise mobilization and 1 h postexercise egress of NK-cells. The blunted exercise response in CMVpos individuals was associated with a decreased relative redeployment of the CD158a+ and CD57+ NK-cell subsets in younger and older individuals. In addition, we show that aging is associated with a CMV-independent increase in the proportion of NK-cells expressing the terminal differentiation marker CD57, while CMV is associated with an age-dependent decrease in the proportion of NK-cells expressing the inhibitory receptors KLRG1 (in the younger group and CD158a (in the older group. Collectively, these data suggest that CMV may decrease NK-cell mediated immunosurveillance after exercise in both younger and older individuals.

  15. Infección congénita por citomegalovirus en recién nacidos del estado de San Luis Potosí, México Congenital cytomegalovirus infection in newborn infants from the state of San Luis Potosí, Mexico

    Directory of Open Access Journals (Sweden)

    Daniel E Noyola

    2011-12-01

    Full Text Available OBJETIVO: Determinar la prevalencia de infección congénita por citomegalovirus en recién nacidos participantes en el programa de tamiz neonatal de los Servicios de Salud de San Luis Potosí. MATERIAL Y MÉTODOS: Se evaluó la presencia de citomegalovirus en muestras de sangre almacenadas en papel filtro. RESULTADOS. Se detectó la presencia de citomegalovirus en 10 (0.68% de 1 457 muestras estudiadas. No se encontraron diferencias en las características de los recién nacidos con infección congénita en comparación con aquéllos sin infección. CONCLUSIONES: Es necesario concientizar a los profesionales de la salud sobre la prevalencia e impacto de la infección congénita por citomegalovirus.OBJECTIVE: To determine the prevalence of congenital cytomegalovirus infection in newborn infants included in the neonatal screening program coordinated by the State Health Services in San Luis Potosí. MATERIAL AND METHODS: We evaluated the presence of cytomegalovirus in blood samples stored in filter paper. RESULTS: Cytomegalovirus was detected in 10 (0.68% of the 1 457 samples included in the study. There were no differences in the characteristics of infants with congenital infection compared to those without infection. CONCLUSIONS: It is necessary to increase awareness of health professionals regarding the prevalence and impact of congenital cytomegalovirus infection.

  16. A Murine Model with Murine Cytomegalovirus Infection Resulting in Colon Inflammation After Allogenetic Skin Transplantation%MCMV感染同种异型皮肤移植小鼠结肠炎模型的建立

    Institute of Scientific and Technical Information of China (English)

    张玮; 甘霖; 黎锐平; 陈敬贤; 王明丽

    2011-01-01

    To provide a reliable animal model for study of human CMV disease in gastrointestinal track, we tried to infect with murine cytomegalovirus (MCMV) in mice that were received allogenetic skin transplantation under immunosuppression. ① Skin transplantation was performed between 18 donor C57BL/6 mice and 72 recipient BALB/c mice. ② All recipient mice were then given Cyclosporine at 12mg/kg daily for 2 weeks by intraperitoneal injection. Mice were randomly divided into 3 groups. Two experimental groups were received MCMV-infected mouse embryonic fibroblasts (MEF) at 104 PFU and 105 PFU respectively,and the control group received MEF only. We observed any possibly pathophysiological behavior changes and recorded the changes in body weight. The mice were sacrificed at 5d, 9d, 14d, 21d post infection and colon tissue was collected for analysis. Results: Mice infected with MCMV at 105PFU group showed anorexia, lethargy and degression in locomotor activity. This group of mice showed significant decrease in body weight than that of other groups. Colon tissues were collected 14 days after infection. Histological examination revealed that the mucous layer became thinner in the proximal colon and increased number of lymphoid follicles in distal colon in infected animals. The changes in the mucosal structure was most prominent in the group 105PFU MCMV. Viral DNA was present in the colon by in situ hybridization for IEl gene, and viral gB transcript was positive by RT-PCR. One of the viral major proteins, pp65, was widely distributed in the colon by immunohistochemistry. These data demonstrated that MCMV established infection in colon of the mice after allogenetic skin transplantation. Electron microscopy showed that there were herpes virus particles in the colon tissue. Conclusion: Infection with MCMV in mouse after allogenetic skin transplantation by nasal cavity inoculation resulted in the pathological changes in colon tissue similar to that of inflammation in human colon

  17. Screening on the risk factors of congenital human cytomegalovirus infection in newborns%新生儿人巨细胞病毒先天性感染危险因素筛查

    Institute of Scientific and Technical Information of China (English)

    汪晓婷; 陈灵芝; 陈敬贤; 王明丽

    2012-01-01

    Objective To screen the congenital human cytomegalovirus (HCMV) infection in newborns. To detect whether there are relationships between the maternal age, HSV- I IgG antibodies, premature and expired births with the congenital human cytomegalovirus infection. Methods To collect the neonatal cord blood from the Maternity and Child Health Hospital from November 2010 to June 2011. Serum HCMV-IgG and HSV- I [gG were screened in 178 cord blood by enzyme-linked immunosorbant assay ( ELISA) , and among them, HCMV DNA were detected by nest-polymerase chain reaction ( nest-PCR). Results The positive rate of HCMV-IgG was 99.44% ( 177/178) : The rate of congenital HCMV infection was 32. 02% (57/178). The positive rate of HSV-1 IgG was 83. 71% (149/178) . Maternal age and HSV-1 IgG antibodies were not risk factors for HCMV congenital transmission. Conclusions Early diagnosis should be strengthened for premature and expired births children about HCMV congenital infection.%目的 通过检测新生儿脐带血中人巨细胞病毒( human cytomegalovirus,HCMV)IgG抗体和gB基因,了解新生儿HCMV感染情况,并结合临床资料分析产妇年龄、Ⅰ型单纯疱疹病毒(herpes simplex virus,HSV-Ⅰ)IgG抗体阳性、孕周与HCMV先天性感染的相关性.方法 收集2010年11月~2011年6月期间,某市妇幼保健院就诊的健康产妇所娩新生儿脐带血,共178例.采用ELISA法检测脐带血血清是否存在HCMVIgG和HSV-Ⅰ IgG抗体,巢式PCR检测HCMV gB基因.结果 产妇HCMVIgG阳性率为99.44% (177/178);产妇HSV-Ⅰ IgG阳性率为83.71% (149/178);新生儿脐血HCMVgB阳性率为32.02% (57/178);产妇年龄和HSV-Ⅰ IgG抗体阳性不是发生HCMV先天性传播的危险因素.结论 针对早产和过期产儿,应该加强其HCMV先天性感染的早期诊断.

  18. Discovery of Potent, Orally Bioavailable Inhibitors of Human Cytomegalovirus.

    Science.gov (United States)

    Fader, Lee; Brault, Martine; Desjardins, Jessica; Dansereau, Nathalie; Lamorte, Louie; Tremblay, Sonia; Bilodeau, François; Bordeleau, Josée; Duplessis, Martin; Gorys, Vida; Gillard, James; Gleason, James L; James, Clint; Joly, Marc-André; Kuhn, Cyrille; Llinas-Brunet, Montse; Luo, Laibin; Morency, Louis; Morin, Sébastien; Parisien, Mathieu; Poirier, Maude; Thibeault, Carl; Trinh, Thao; Sturino, Claudio; Srivastava, Sanjay; Yoakim, Christiane; Franti, Michael

    2016-05-12

    A high-throughput screen based on a viral replication assay was used to identify inhibitors of the human cytomegalovirus. Using this approach, hit compound 1 was identified as a 4 μM inhibitor of HCMV that was specific and selective over other herpes viruses. Time of addition studies indicated compound 1 exerted its antiviral effect early in the viral life cycle. Mechanism of action studies also revealed that this series inhibited infection of MRC-5 and ARPE19 cells by free virus and via direct cell-to-cell spread from infected to uninfected cells. Preliminary structure-activity relationships demonstrated that the potency of compound 1 could be improved to a low nanomolar level, but metabolic stability was a key optimization parameter for this series. A strategy focused on minimizing metabolic hydrolysis of the N1-amide led to an alternative scaffold in this series with improved metabolic stability and good pharmacokinetic parameters in rat. PMID:27190604

  19. Cytomegalovirus as an Insidious Pathogen Causing Duodenitis

    OpenAIRE

    Hagiya, Hideharu; Iwamuro, Masaya; Tanaka, Takehiro; Hanayama, Yoshihisa; Otsuka, Fumio

    2015-01-01

    A 60-year-old woman with rheumatoid arthritis treated with methotrexate for a decade complained of slight epigastric discomfort. A positive cytomegalovirus (CMV) antigenemia test indicated the probability of CMV-related gastrointestinal infection, for which esophagogastroduodenoscopy was performed. Endoscopic findings showed a non-specific duodenal mucosal lesion;however, pathological investigation revealed evidence of CMV duodenitis. There is scarce information on the clinical and pathologic...

  20. Maturation and Mip-1β Production of Cytomegalovirus-Specific T Cell Responses in Tanzanian Children, Adolescents and Adults: Impact by HIV and Mycobacterium tuberculosis Co-Infections.

    Directory of Open Access Journals (Sweden)

    Damien Portevin

    Full Text Available It is well accepted that aging and HIV infection are associated with quantitative and functional changes of CMV-specific T cell responses. We studied here the expression of Mip-1β and the T cell maturation marker CD27 within CMVpp65-specific CD4(+ and CD8(+ T cells in relation to age, HIV and active Tuberculosis (TB co-infection in a cohort of Tanzanian volunteers (≤ 16 years of age, n = 108 and ≥ 18 years, n = 79. Independent of HIV co-infection, IFNγ(+ CMVpp65-specific CD4(+ T cell frequencies increased with age. In adults, HIV co-infection further increased the frequencies of these cells. A high capacity for Mip-1β production together with a CD27(low phenotype was characteristic for these cells in children and adults. Interestingly, in addition to HIV co-infection active TB disease was linked to further down regulation of CD27 and increased capacity of Mip-1β production in CMVpp65-specific CD4+ T cells. These phenotypic and functional changes of CMVpp65-specific CD4 T cells observed during HIV infection and active TB could be associated with increased CMV reactivation rates.

  1. The Expression of Human Cytomegalovirus MicroRNA MiR-UL148D during Latent Infection in Primary Myeloid Cells Inhibits Activin A-triggered Secretion of IL-6.

    Science.gov (United States)

    Lau, Betty; Poole, Emma; Krishna, Benjamin; Sellart, Immaculada; Wills, Mark R; Murphy, Eain; Sinclair, John

    2016-08-05

    The successful establishment and maintenance of human cytomegalovirus (HCMV) latency is dependent on the expression of a subset of viral genes. Whilst the exact spectrum and functions of these genes are far from clear, inroads have been made for protein-coding genes. In contrast, little is known about the expression of non-coding RNAs. Here we show that HCMV encoded miRNAs are expressed de novo during latent infection of primary myeloid cells. Furthermore, we demonstrate that miR-UL148D, one of the most highly expressed viral miRNAs during latent infection, directly targets the cellular receptor ACVR1B of the activin signalling axis. Consistent with this, we observed upregulation of ACVR1B expression during latent infection with a miR-UL148D deletion virus (ΔmiR-UL148D). Importantly, we observed that monocytes latently infected with ΔmiR-UL148D are more responsive to activin A stimulation, as demonstrated by their increased secretion of IL-6. Collectively, our data indicates miR-UL148D inhibits ACVR1B expression in latently infected cells to limit proinflammatory cytokine secretion, perhaps as an immune evasion strategy or to postpone cytokine-induced reactivation until conditions are more favourable. This is the first demonstration of an HCMV miRNA function during latency in primary myeloid cells, implicating that small RNA species may contribute significantly to latent infection.

  2. Receptor expression and responsiveness of human peripheral blood mononuclear cells to a human cytomegalovirus encoded CC chemokine

    Directory of Open Access Journals (Sweden)

    Qi Zheng

    2015-08-01

    Full Text Available Human cytomegalovirus is a ubiquitous pathogen that infects the majority of the world's population. After long period of time co-evolving with human being, this pathogen has developed several strategies to evade host immune surveillance. One of the major trick is encoding homologous to those of the host organism or stealing host cellular genes that have significant functions in immune system. To date, we have found several viral immune analogous which include G protein coupled receptor, class I major histocompatibility complex and chemokine. Chemokine is a small group of molecules which is defined by the presence of four cysteines in highly conserved region. The four kinds of chemokines (C, CC, CXC, and CX3C are classified based on the arrangement of 1 or 2 N-terminal cysteine residues. UL128 protein is one of the analogous that encoded by human cytomegalovirus that has similar amino acid sequences to the human CC chemokine. It has been proved to be one of the essential particles that involved in human cytomegalovirus entry into epithelial/endothelial cells as well as macrophages. It is also the target of potent neutralizing antibodies in human cytomegalovirus-seropositive individuals. We had demonstrated the chemotactic trait of UL128 protein in our previous study. Recombinant UL128 in vitrohas the ability to attract monocytes to the infection region and enhances peripheral blood mononuclear cell proliferation by activating the MAPK/ERK signaling pathway. However, the way that this viral encoded chemokine interacting with peripheral blood mononuclear cells and the detailed mechanism that involving the virus entry into host cells keeps unknown. Here we performed in vitroinvestigation into the effects of UL128 protein on peripheral blood mononuclear cell's activation and receptor binding, which may help us further understand the immunomodulatory function of UL128 protein as well as human cytomegalovirus diffusion mechanism.

  3. Cytomegalovirus Immunoglobulin After Thoracic Transplantation

    Science.gov (United States)

    Grossi, Paolo; Mohacsi, Paul; Szabolcs, Zoltán; Potena, Luciano

    2016-01-01

    Abstract Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R−). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation. PMID:26900989

  4. Does cytomegalovirus predict a poor prognosis in Pneumocystis carinii pneumonia treated with corticosteroids? A note for caution

    DEFF Research Database (Denmark)

    Jensen, A M; Lundgren, Jens Dilling; Benfield, T;

    1995-01-01

    OBJECTIVE: To examine the importance of cytomegalovirus (CMV) in bronchoalveolar lavage (BAL) fluid of patients with HIV-associated Pneumocystis carinii pneumonia (PCP) treated with adjunctive corticosteroids (CS). DESIGN: Analysis of clinical data during a 5-year period. SETTING: Department of i...... of adjunctive CS in severe PCP, the role of CMV as a pulmonary copathogen may have changed. Active CMV infection may be an important cause of failing treatment of severe PCP in those treated with adjunctive CS....

  5. Cytomegalovirus Hepatitis During Pregnancy

    Directory of Open Access Journals (Sweden)

    Ying Chan

    1995-01-01

    Full Text Available Background: Although cytomegalovirus (CMV is an uncommon cause of viral hepatitis during pregnancy, a definitive diagnosis is important because of the potential for congenital CMV. In the case reported here, a diagnosis of hepatitis caused by CMV was made after the more common viral pathogens had been ruled out.

  6. HCMV 持续性感染对 BALB/c 小鼠中枢神经系统的影响%The effects of human cytomegalovirus persistent infection on the central nervous system of BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    张俊玲; 黄维; 刘倩; 王明丽

    2014-01-01

    Objective To investigate the effects of human cytomegalovirus ( HCMV) persistent in-fection on the central nervous system of BALB/c mice.Methods Thirty specific-pathogen-free mice of 6-8 weeks old were randomly divided into three groups including HCMV infected group , inactivated HCMV group and human embryo fibroblast ( HF) control group .Each mouse in the three groups was intraperitoneally inoc-ulated with 1.8 ×107 PFU of HCMV, 1.8 ×107 PFU inactivated HCMV and 1 ×105 HF cells, respectively. All mice were housed in microisolator cages for three months and their behavior and body weight were ob -served.Then three tests including autonomic activities test , Morris Water Maze and step-down passive avoid-ance task were performed on all mice to evaluate the changes of their behavior .Cerebral cortex tissues were collected from all mice to detect HCMV and to conduct polymerase chain reaction (PCR) analysis.Brain tis-sues were stained by HE method to evaluate the pathological damages .Transmission electron microscope was used to observe the ultrastructure of neuron cells and the existence of virus particles .Results (1) The body weight of mice showed no significant differences among the three groups ( P>0 .05 ) .( 2 ) The frequency of autonomic activities were decreases in HCMV infected group in comparison with other two groups , but there was no significant differences among the three groups (P>0.05).(3)The place navigation test demonstra-ted that the escape latency of mice from HCMV infected group as well as HF group showed significant differ -ence after training for different periods of time (P0.05).Compared with the mice in two control groups , the mice in HCMV infected group showed a lower frequency of crossing the quadrant where the platform had been located on pre -vious trials in the probe trial test (P<0.05).Moreover, the time of first crossings was also longer than that of mice from two control groups (P<0.05).(4)In the learning phase the mice from HCMV

  7. Evaluation of a standardised real-time PCR based DNA-detection method (Realstar®) in whole blood for the diagnosis of primary human cytomegalovirus (CMV) infections in immunocompetent patients.

    Science.gov (United States)

    Berth, M; Benoy, I; Christensen, N

    2016-02-01

    Cytomegalovirus (CMV) DNA detection in blood could, as a supplementary test to serology, improve the accuracy and speed of diagnosis of an acute CMV infection. In this study we evaluated the performance of a commercially available and standardised CMV PCR assay in whole blood for the diagnosis of a primary infection in immunocompetent adults. Moreover, the kinetics of viral DNA was evaluated in order to provide a time frame in which viral DNA could be detected during an acute primary infection. Whole blood samples were collected from 66 patients with an acute CMV infection, 65 patients with an acute Epstein-Barr virus infection, 27 patients with various other acute infections (parvovirus B19, HIV, Toxoplasma gondii), 20 patients with past CMV infections (>1 year) and 20 apparently healthy persons. For CMV DNA detection and quantification a commercially available real-time PCR was applied (RealStar®, altona Diagnostics). The clinical sensitivity of CMV PCR in whole blood for the diagnosis of a recent primary CMV infection was 93.9 % and the diagnostic specificity 99.2 %. In the majority of the patients CMV DNA was not detectable anymore approximately within 4 weeks after the first blood sample was taken. From these data we concluded that, together with a suggestive serological profile, a positive CMV PCR result in whole blood can be regarded as a diagnostic confirmation of a recent CMV infection on a single blood sample in an immunocompetent patient. However, a negative CMV PCR result does not exclude a recent CMV infection. PMID:26661089

  8. Ulcerative colitis after Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Mohammad Aminianfar

    2014-06-01

    Full Text Available A 21 years old man has been complained of bloody diarrhea, liquid stool containing blood, pus, and fecal matter and crampy abdominal pain from four monthes ago. Ulcerative colitis relies upon the patient's history, clinical symptoms, sigmoidoscopic appearance and histology of colonic biopsy specimens. Treatment of patient started with high dose dexamethasone and prednisolone, asacole, suppository, metronidazole. Patient’s condition not improved and patient admitted in hospital. High dose prednisolone, azathioprine, sulfasalazine and folic acid were given.

  9. Neurological Consequences of Cytomegalovirus Infection

    Science.gov (United States)

    ... may affect the brain (encephalitis), spinal cord (myelitis), eye (retinitis), or other organs such as the lungs (pneumonia) or intestinal gract (gastritis, enteritis, or colitis). In addition, transplant recipients may develop organ rejection or graft-versus- ...

  10. Study of seroprevalance of Toxoplasma gondii, Rubella virus and Cytomegalovirus (ToRC infections in antenatal women presented with bad obstetric history and comparative evaluation of Nanoplex ToRCH screen ELISA kit with VIDAS

    Directory of Open Access Journals (Sweden)

    Susmitha Simgamsetty

    2015-05-01

    Full Text Available Background: Infections caused by Toxoplasma gondii, Rubella virus and Cytomegalovirus are major causes of Bad Obstetric History (BOH. Cause of BOH may be genetic, hormonal, abnormal maternal immune response, and maternal infection. Women affected with any of these diseases during pregnancy are at high risk for miscarriage, stillbirth, or for a child with serious birth defects and/or illness and also a hazard to attending staff nurses. Methods: A total 96 serum samples were collected from antenatal women with BOH attending the out-patient services of department of gynaecology at NRI general hospital, Chinakakani, Guntur district, Andhra Pradesh. Serum samples were obtained and were subjected to screening for Immunoglobulin M (IgM and Immunoglobulin G (IgG antibodies of Toxopalsma gondii, Rubella Virus and CMV infections by VIDAS (bioMerieux, France and Nanoplex ToRCH Screen kit [Lilac Medicare (P Ltd, Maharastra, India]. Results: Majority of cases with BOH were found in females aged 18-23 years (25, 52.08% followed by 24-29 years (18, 37.5%. Congenital anomalies and other complications were found to be more in age group 18-23 years followed by 24-29 years. The disease prevalence as studied with respect to IgM antibodies was found to be 31.25% for Cytomegalovirus Infections, 23.96% for Toxoplasma gondii, 21.88% for Rubella virus infections. The overall agreement in the Sensitivity, Specificity, Positive Predictive Value (PPV and Negative Predictive Value (NPV between VIDAS and Nanoplex ToRCH Screen kit for the detection of specific IgM and IgG antibodies in our study was excellent with sensitivity ranging from 90.91%-96.00% and specificity ranging from 89.47%-95.59% for the detection of IgM and IgG antibodies. The discrepancies were relatively less with 8.3% for CMV IgM, 6.2% for CMV IgG, 5.20% for Rubella IgM, 6.25% for Rubella IgG, 6.25% for Toxo IgM and 5.20% for Toxo IgG. Conclusion: Nanoplex ToRCH Screen Kit is a cheap, cost effective

  11. Screening, prevention, and treatment of congenital cytomegalovirus.

    Science.gov (United States)

    Johnson, Julie; Anderson, Brenna

    2014-12-01

    Congenital cytomegalovirus (CMV) is a leading cause of permanent disability in children. The main source of maternal infection is from contact with young children. Primary maternal infection is diagnosed with demonstration of seroconversion or a positive CMV IgM in combination with a low-avidity CMV IgG. Fetal infection may be diagnosed with amniotic fluid polymerase chain reaction and culture. CMV-specific hyperimmune globulin has shown promise as a possible means to prevent congenital infection; large randomized trials are ongoing. To date, the only effective means of prevention is through reducing exposure to the virus. Rates of maternal infection may be reduced through education regarding sources of infection and improved hygiene.

  12. Human cytomegalovirus-encoded miR-US4-1 promotes cell apoptosis and benefits discharge of infectious virus particles via down-regulation of glutaminyl-tRNA synthetase, QARS in HCMV-infected HELF cells

    Indian Academy of Sciences (India)

    Yaozhong Shao; Ying Qi; Yujing Huang; Zhongyang Liu; Yanping Ma; Xin Guo; Shujuan Jiang; Zhengrong Sun; Qiang Ruan

    2016-06-01

    Human cytomegalovirus (HCMV) can cause congenital diseases and opportunistic infections in immunocompromised individuals. Its functional proteins and microRNAs (miRNAs) facilitate efficient viral propagation by altering host cell behaviour. Identification of functional target genes of miRNAs is an important step in studies on HCMV pathogenesis. In this study, Glutaminyl-tRNA Synthetase (QARS), which could regulate signal transduction pathways for cellular apoptosis, was identified as a direct target of hcmv-miR-US4-1. Apoptosis assay revealed that as silence of QARS by ectopic expression of hcmv-miR-US4-1 and specific small interference RNA of QARS can promote cell apoptosis in HCMV-infected HELF cells. Moreover, viral growth curve assays showed that hcmv-miR-US4-1 benefits the discharge of infectious virus particles. However, silence of hcmv-miR-US4-1 by its specific inhibitor overturned these effects. These results imply that hcmv-miR-US4-1 might have the same effects during HCMV nature infection. In general, hcmv-miR-US4-1 may involve in promoting cell apoptosis and benefiting discharge of infectious virus particles via down-regulation of QARS in HCMV-infected HELF cells.

  13. The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain.

    Science.gov (United States)

    Steingruber, Mirjam; Socher, Eileen; Hutterer, Corina; Webel, Rike; Bergbrede, Tim; Lenac, Tihana; Sticht, Heinrich; Marschall, Manfred

    2015-08-11

    Replication of human cytomegalovirus (HCMV) is characterized by a tight virus-host cell interaction. Cyclin-dependent protein kinases (CDKs) are functionally integrated into viral gene expression and protein modification. The HCMV-encoded protein kinase pUL97 acts as a CDK ortholog showing structural and functional similarities. Recently, we reported an interaction between pUL97 kinase with a subset of host cyclins, in particular with cyclin T1. Here, we describe an interaction of pUL97 at an even higher affinity with cyclin B1. As a striking feature, the interaction between pUL97 and cyclin B1 proved to be strictly dependent on pUL97 activity, as interaction could be abrogated by treatment with pUL97 inhibitors or by inserting mutations into the conserved kinase domain or the nonconserved C-terminus of pUL97, both producing loss of activity. Thus, we postulate that the mechanism of pUL97-cyclin B1 interaction is determined by an active pUL97 kinase domain.

  14. Organ damage and genotypes of infantile cytomegalovirus infection%婴幼儿巨细胞病毒感染器官损害与基因型

    Institute of Scientific and Technical Information of China (English)

    李梨平; 覃亚斌; 祝兴元; 朱纯华; 周峥珍; 范丽明; 李小曼

    2013-01-01

    Objective To investigate the association between serum antibodies or glycoprotein B (gB) genotype of human cytomegalovirus (HCMV) with liver damage or birth delect. Methods From January 2009 to December 2010, 337 hospitalized inlants whose serum HCMV IgG antibody was positive and HCMV DNA in urine exceeded 500 copies/mL were included in the study. HCMV antibodies (IgG, IgM) of inlants and mothers were detected by capture enzyme-linked immunosorbent assay; HCMV DNA in infants were detected by real-time polymerase chain reaction; HCMV from clinical specimens were cultured in human embryonic lung fibroblasts; HCMV gB was geno-typed by nested PCR-restriction fragment length polymorphism Results Of 337 infants infected with HCMV, serum HCMV antibodies of 124 were both IgM( + ) and IgG( + ), liver damage rate and birth defect rate were higher in infants whose mothers'HCMV IgG were negative than that were positive(86. 42% vs 65. 12% for liver damage.40. 74% vs 34. 88% lor birth delect, P<0. 01) ; Serum HCMV antibodies were IgM( - ) and IgG( + ) in 213 infants, liver damage rate in infants whose mothers'serum antibodies were lgG( + ) was not significantly different compared with that were IgG( - ) (53. 85% vs 66. 89%, P>0. 05) , but birth defect rate in IgG( - ) group was higher than IgG ( + ) group (28. 38% vs 23. 08%, P<0. 05). Isolation rate ol HCMV Irom urine was 50. 00% (31/ 62) in inlants whose HCMV IgG were positive and urine HCMV DNA≥104 copies/mL. g'B genotype of 8 randomly selected HCMV strains(7 were from infants with liver or brain damage) were all gBl, compared with AD169 or TOWNE strain, DNA sequence homology was 94. 8% and 97. 0% respectively, homology of DNA sequence among 8 strains was 98. 5% ,and amino sequence was 99. 4%. Conclusion The liver damage and birth defect are lower in infants whose mothers' HCMV IgG were positive than that were negative. Urine HCMV DNA ≥104 copies/mL in infants can be a marker for HCMV infection. gBl may be the main

  15. Antiviral treatment in patients with cytomegalovirus positive ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Kadir; Ozturk

    2014-01-01

    Cytomegalovirus(CMV) is a common virus in patients with ulcerative colitis receiving immunosuppressive drugs. Many studies suggested that CMV infection is an exacerbating factor in patients with ulcerative colitis. The role of CMV in exacerbations of ulcerative colitis has been discussed. One of studies starting this discussion is an article entitled "CMV positive ulcerative colitis: A single center experience and literature review" by Kopylov et al. However, we think that there are some points that should be emphasized about the study. Especially, the small number of patients in the study has led to meaningless results. Large controlled prospective trials are needed to clarify the benefit of antiviral therapy for active ulcerative colitis patients.

  16. Cytomegalovirus and ulcerative colitis: Place of antiviral therapy.

    Science.gov (United States)

    Pillet, Sylvie; Pozzetto, Bruno; Roblin, Xavier

    2016-02-14

    The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis (UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools (numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flare-ups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease. PMID:26877608

  17. The Cell Biology of Cytomegalovirus: Implications for Transplantation.

    Science.gov (United States)

    Kaminski, H; Fishman, J A

    2016-08-01

    Interpretation of clinical data regarding the impact of cytomegalovirus (CMV) infection on allograft function is complicated by the diversity of viral strains and substantial variability of cellular receptors and viral gene expression in different tissues. Variation also exists in nonspecific (monocytes and dendritic cells) and specific (NK cells, antibodies) responses that augment T cell antiviral activities. Innate immune signaling pathways and expanded pools of memory NK cells and γδ T cells also serve to amplify host responses to infection. The clinical impact of specific memory T cell anti-CMV responses that cross-react with graft antigens and alloantigens is uncertain but appears to contribute to graft injury and to the abrogation of allograft tolerance. These responses are modified by diverse immunosuppressive regimens and by underlying host immune deficits. The impact of CMV infection on the transplant recipient reflects cellular changes and corresponding host responses, the convergence of which has been termed the "indirect effects" of CMV infection. Future studies will clarify interactions between CMV infection and allograft injury and will guide interventions that may enhance clinical outcomes in transplantation.

  18. Reconstitution of Human Cytomegalovirus-Specific CD4+ T Cells is Critical for Control of Virus Reactivation in Hematopoietic Stem Cell Transplant Recipients but Does Not Prevent Organ Infection.

    Science.gov (United States)

    Gabanti, Elisa; Lilleri, Daniele; Ripamonti, Francesco; Bruno, Francesca; Zelini, Paola; Furione, Milena; Colombo, Anna A; Alessandrino, Emilio P; Gerna, Giuseppe

    2015-12-01

    The relative contribution of human cytomegalovirus (HMCV)-specific CD4(+) and CD8(+) T cells to the control of HCMV infection in hematopoietic stem cell transplant (HSCT) recipients is still controversial. HCMV reactivation and HCMV-specific CD4(+) and CD8(+) T cell reconstitution were monitored for 1 year in 63 HCMV-seropositive patients receiving HSCT. HCMV reactivation was detected in all but 2 patients. In 20 of 63 (31.7%) patients (group 1) HCMV infection resolved spontaneously, whereas 32 of 63 (50.8%) patients (group 2) controlled the infection after a single short-course of pre-emptive therapy and the remaining 9 (14.3%) patients (group 3) suffered from relapsing episodes of HCMV infection, requiring multiple courses of antiviral therapy. The kinetics and magnitude of HCMV-specific CD8(+) T cell reconstitution were comparable among the 3 groups, but HCMV-specific CD4(+) T cells were lower in number in patients requiring antiviral treatment. HCMV-seronegative donors, as well as unrelated donors (receiving antithymocyte globulin) and acute graft-versus-host disease (GVHD) were associated with both delayed HCMV-specific CD4(+) T cell reconstitution and severity of infection. Conversely, these risk factors had no impact on HCMV-specific CD8(+) T cells. Eight patients with previous GVHD suffered from HCMV gastrointestinal disease, although in the presence of HCMV-specific CD4(+) and CD8(+) systemic immunity and undetectable HCMV DNA in blood. Reconstitution of systemic HCMV-specific CD4(+) T cell immunity is required for control of HCMV reactivation in adult HSCT recipients, but it may not be sufficient to prevent late-onset organ localization in patients with GVHD. HCMV-specific CD8(+) T cells contribute to control of HCMV infection, but only after HCMV-specific CD4(+) T cell reconstitution.

  19. 围生期巨细胞病毒感染监测与预后评估%Progress or screening and prognosis evaluation of cytomegalovirus infection in perinatal period

    Institute of Scientific and Technical Information of China (English)

    王丽

    2012-01-01

    Cytomegalovirus (CMV),a DNA herpusvirusesw,is the most common virus leading to intrauterine infetcion.It is transmitted from mother to fetus through placenta,and the neonates who suffering from congenital symptomatic infections may have sensorineural hearing loss,hepatosplenomegaly,microcephaly,chorioretinitis etc.Studies have suggested that the characters of infections on pregnant women,such as the time of infection,the serological results and virus load in amniotic fluid are associated with the outcome of offsprings.This paper is to review the risk of CMV infections on women at childbearing age,screening of CMV infections on pregnant women and the prenatal diagonosis of fetal CMV infection.%巨细胞病毒属于疱疹病毒,可通过胎盘传播给胎儿,是宫内感染最常见的病原体.巨细胞病毒感染可导致新生儿症状性感染,主要表现为感觉神经性耳聋、肝脾肿大、小头畸形、脉络膜视网膜炎等.研究表明妊娠妇女巨细胞病毒感染特征,如感染的时间、血清学结果、羊水中病毒载量等与子代结局关系密切.该文就育龄期妇女感染巨细胞病毒的高危因素、妊娠妇女感染筛查以及胎儿宫内感染诊断及预后评价的进展作一综述.

  20. Childhood environments and cytomegalovirus serostatus and reactivation in adults

    NARCIS (Netherlands)

    D. Janicki-Deverts; S. Cohen; W.J. Doyle; A.L. Marsland; J. Bosch

    2014-01-01

    Childhood adversity, defined in terms of material hardship or physical or emotional maltreatment has been associated with risk for infection with cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation in children and adults. The present study examined whether different dimen

  1. Complement activation in experimental human malaria infection.

    NARCIS (Netherlands)

    Roestenberg, M.; McCall, M.B.B.; Mollnes, T.E.; Deuren, M. van; Sprong, T.; Klasen, I.S.; Hermsen, C.C.; Sauerwein, R.W.; Ven, A.J.A.M. van der

    2007-01-01

    The objective of this study was to investigate complement activation in uncomplicated, early phases of human malaria. Fifteen healthy volunteers were experimentally infected with Plasmodium falciparum malaria. Parasitemia and complement activation products were assessed. During blood stage parasitem

  2. Changes of Th1/Th2 cytokines in cytomegalovirus infected infant%Th1/Th2细胞因子在儿童巨细胞病毒感染中的变化

    Institute of Scientific and Technical Information of China (English)

    何强; 幺远; 胡艳

    2013-01-01

    Cytomegalovirus (CMV) is one of the herpesviruses. Infant may develop a serious disease with a weakened immune system due to the virus. Cytokines reflect the immune function changes. This article described the changes of Thl/ Th2 cytokines in CMV infected infants, and provided suggestions for future research and clinical treatment of CMV infection.%巨细胞病毒(CMV)属于β疱疹病毒亚科,儿童普遍易感,并可引起部分感染患儿发育异常及脏器损害.CMV感染常引起一系列免疫反应,导致机体免疫功能异常.细胞因子参与了CMV感染的发生发展过程.文章描述并讨论在儿童CMV感染中Th1/Th2细胞因子的变化,为儿童CMV的研究及临床治疗提供思路.

  3. Modulation of HLA Expression in Human Cytomegalovirus Immune Evasion

    Institute of Scientific and Technical Information of China (English)

    Aifen Lin; Huihui Xu; Weihua Yan

    2007-01-01

    Human cytomegalovirus (hCMV) has evolved multiple mechanisms to escape the host immune recognition and innate or adaptive immune responses. Among them, hCMV has developed strategies to modulate the expression and/or function of human leukocyte antigens (HLAs), including by encoding series of infection stage-dependent hCMV proteins to detain and destroy the expression of HLA molecules on the surface of infected cells. This disturbs the antigen presentation and processing, by encoding MHC class Ⅰ homologues or selective up-regulation of particular HLA class Ⅰ molecules binding to NK cell inhibitory receptors, and by encoding specific ligand antagonists to interfere with NK cell activating receptors. Here we discussed the molecular mechanisms utilized by the hCMV to alter the formation, transportation and expression of HLA antigens on the infected cell surface. The knowledge about hCMV modulating HLA expression could benefit us to further understand the pathogenesis of viral diseases and may eventually develop novel effective immunotherapies to counteract viral infections and viral associated diseases.

  4. Human cytomegalovirus and Epstein-Barr virus infection impact on {sup 18}F-FDG PET/CT SUVmax, CT volumetric and KRAS-based parameters of patients with locally advanced rectal cancer treated with neoadjuvant therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sole, Claudio V. [Instituto de Radiomedicina, Department of Radiation Oncology, Santiago (Chile); School of Medicine Complutense University, Madrid (Spain); Calvo, Felipe A. [Hospital General Universitario Gregorio Maranon, Department of Oncology, Madrid (Spain); School of Medicine Complutense University, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Institute for Sanitary Research, Madrid (Spain); Ferrer, Carlos [Hospital Provincial de Castellon, Institute of Oncology, Castellon de la Plana (Spain); School of Medicine Cardenal Herrera-CEU University, Castellon de la Plana (Spain); Alvarez, Emilio [School of Medicine Complutense University, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Department of Pathology, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Institute for Sanitary Research, Madrid (Spain); Carreras, Jose L. [School of Medicine Complutense University, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Department of Radiology and Medical Physics, Madrid (Spain); Ochoa, Enrique [Hospital Provincial de Castellon, Institute of Oncology, Castellon de la Plana (Spain)

    2014-10-01

    It has long been debated whether human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are associated with rectal cancer. The gene products of HCMV and EBV contribute to cell-cycle progression, mutagenesis, angiogenesis and immune evasion. The aim of this prospective study was to analyse the association between infection of a tumour by HCMV and EBV and clinical, histological, metabolic ({sup 18}F-FDG uptake), volumetric (from CT) and molecular (KRAS status) features and long-term outcomes in a homogeneously treated group of patients with locally advanced rectal cancer. HCMV and EBV were detected in pretreatment biopsies using polymerase chain reaction (PCR). The Cox proportional hazards regression model was used to explore associations between viral infection and disease-free survival (DFS) and overall survival (OS). We analysed 37 patients with a median follow-up of 74 months (range 5-173 months). Locoregional control, OS and DFS at 5 years were 93 %, 74 % and 71 %, respectively. Patients with HCMV/EBV coinfection had a significantly higher maximum standardized uptake value than patients without viral coinfection (p = 0.02). Significant differences were also observed in staging and percentage relative reduction in tumour volume between patients with and without HCMV infection (p < 0.01) and EBV infection (p < 0.01). KRAS wildtype status was significantly more frequently observed in patients with EBV infection (p <0.01) and HCMV/EBV co-infection (p = 0.04). No significant differences were observed in OS or DFS between patients with and without EBV infection (p = 0.88 and 0.73), HCMV infection (p = 0.84 and 0.79), and EBV/CMV coinfection (p = 0.24 and 0.39). This pilot study showed that viral infections were associated with metabolic staging differences, and differences in the evolution of metabolic and volumetric parameters and KRAS mutations. Further findings of specific features will help determine the best candidates for metabolic and volumetric staging and

  5. Murine cytomegalovirus immediate-early 1 gene expression correlates with increased GVHD after allogeneic hematopoietic cell transplantation in recipients reactivating from latent infection.

    Directory of Open Access Journals (Sweden)

    Senthilnathan Palaniyandi

    Full Text Available The success of allogeneic (allo hematopoietic cell transplantation (HCT is limited by its treatment related complications, mostly graft versus host disease (GVHD and fungal and viral infections. CMV reactivation after HCT has been associated with increased morbidity and mortality, and a causal relation between GVHD, immunosuppressive therapy and vice versa has been postulated. Using a low GVHD severity murine HCT model, we assessed the role of MCMV reactivation and GVHD development. BALB/c mice were infected with either murine CMV (MCMV or mock and monitored for 25 weeks to establish latency, followed by sublethal irradiation conditioning and infusion of bone marrow plus splenocytes from either syngeneic (syn BALB/c or allo B10.D2 donors. Engraftment of allo donor cells was confirmed by PCR for D2Mit265 gene product size. Day+100 mortality and overall GVHD severity in allo MCMV pre-infected recipients was higher than in allo mock controls. Pathologic changes of lung and liver GVHD in immediate-early gene 1 (IE1 positive recipients were significantly increased compared to mock controls, and were only slightly increased in IE1 negative. No significant gut injury was seen in any group. Aggravated lung injury in IE1 positive recipients correlated with higher BAL cell counts both for total cells and for CD4+ T cells when compared with mock controls, and also with protein expression of lung IFN-gamma and liver TNF. No evidence for CMV specific morphologic changes was seen on histopathology in any organ of IE1 positive recipients, suggesting that CMV reactivation is related to increased GVHD severity but does not require active CMV disease, strengthening the concept of a reciprocal relationship between CMV and GVHD.

  6. SEROEPIDEMIOLOGY OF TOXOPLASMA, RUBELLA, CYTOMEGALOVIRUS AND HERPES SIMPLEX VIRUS -2 IN WOMEN WITH BAD OBSTETRIC HISTORY. PART I: TOXOPLASMA AND RUBELLA INFECTIONS

    Directory of Open Access Journals (Sweden)

    Abdulghani Mohamed Alsamarai

    2013-10-01

    Full Text Available Bad obstetric history (BOH is associated with social and psychological impacts on society worldwide. The causes of BOH may be genetic, hormonal, abnormal maternal immune response, and maternal infection. In women with bad obstetric history (BOH, Toxoplasma (T IgG high rate has been reported for Nepal (55.2%, while high (42.5% and lowest (6.97% active toxoplasma infections has been reported for India. In Arab countries, IgG and IgM higher and lowest seroprevalence rates were for Iraq. The higher susceptibility rates for Rubella in Arab countries excluding Iraq were reported in Morocco (83.4%, Sudan (34.7%, Qatar (25.1%, and Tunisia (20.3%. The lowest susceptibility was reported for Saudi Arabia (6.7%. In Iraq, studies indicate a high susceptibility rates in Thi Qar (98.05%, Kirkuk (91%, Baghdad (79%, and Waset (45.7%. The lowest susceptibility rates were reported for Diyala (0% in women with previous abortion, and 3.9% in pregnant women without history of BOH.

  7. ANTIVIRAL EFFECTS OF PLASMA AND MILK-PROTEINS - LACTOFERRIN SHOWS POTENT ACTIVITY AGAINST BOTH HUMAN-IMMUNODEFICIENCY-VIRUS AND HUMAN CYTOMEGALOVIRUS REPLICATION IN-VITRO

    NARCIS (Netherlands)

    HARMSEN, MC; SWART, PJ; DEBETHUNE, MP; PAUWELS, R; DECLERCQ, E; THE, TH; MEIJER, DKF

    1995-01-01

    Native and chemically derivatized proteins purified from serum and milk were assayed in vitro to assess their inhibiting capacity on the cytopathic effect of human immunodeficiency virus (HIV)-1 and human cytomegalovirus (HCMV) on MT4 cells and fibroblasts, respectively. Only native and conformation

  8. Cytomegalovirus as an Insidious Pathogen Causing Duodenitis.

    Science.gov (United States)

    Hagiya, Hideharu; Iwamuro, Masaya; Tanaka, Takehiro; Hanayama, Yoshihisa; Otsuka, Fumio

    2015-01-01

    A 60-year-old woman with rheumatoid arthritis treated with methotrexate for a decade complained of slight epigastric discomfort. A positive cytomegalovirus (CMV) antigenemia test indicated the probability of CMV-related gastrointestinal infection, for which esophagogastroduodenoscopy was performed. Endoscopic findings showed a non-specific duodenal mucosal lesion;however, pathological investigation revealed evidence of CMV duodenitis. There is scarce information on the clinical and pathological features of CMV-related duodenitis, likely due to its low prevalence. CMV infection in the upper gastrointestinal tract should be considered as a differential diagnosis in high-risk individuals, particularly those with symptoms relating to the digestive system. Biopsy examinations are preferable for the definitive diagnosis of CMV gastrointestinal infection, even without specific endoscopic features. PMID:26490030

  9. Rapid detection of cytomegalovirus in bronchoalveolar lavage fluid and serum samples by polymerase chain reaction: correlation of virus isolation and clinical outcome for patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Hansen, K K; Vestbo, Jørgen; Benfield, T;

    1997-01-01

    Bronchoalveolar lavage (BAL) fluids and serum samples from 153 patients with pulmonary symptoms who were infected with human immunodeficiency virus (HIV) and underwent BAL were examined for the presence of cytomegalovirus (CMV) by conventional culture and by polymerase chain reaction (PCR......) for detection of CMV DNA. PCR detected CMV more frequently than did cultures of BAL fluid (PCR of BAL fluid, 53%; PCR of serum, 40%; and culture, 30%). In a multivariate model, development of extrapulmonary CMV disease was predicted by the finding of CMV in BAL fluid by culture (relative risk [RR], 8.......0; confidence interval [CI], 3.8-16.8) or the finding of CMV DNA in serum (RR, 7.4; CI, 3.2-17.3) or BAL fluid (RR, 8.0; CI, 3.1-20.7) by PCR. Mortality was found to be similar for patients who did or did not have CMV detected by either culture or PCR. Detection of CMV DNA by PCR was a more rapid and sensitive...

  10. The tiers and dimensions of evasion of the type I interferon response by human cytomegalovirus.

    Science.gov (United States)

    Amsler, Lisi; Verweij, Marieke C; DeFilippis, Victor R

    2013-12-13

    Human cytomegalovirus (HCMV) is a member of the β-herpesvirus family that invariably occupies hosts for life despite a consistent multi-pronged antiviral immune response that targets the infection. This persistence is enabled by the large viral genome that encodes factors conferring a wide assortment of sophisticated, often redundant phenotypes that disable or otherwise manipulate impactful immune effector processes. The type I interferon system represents a first line of host defense against infecting viruses. The physiological reactions induced by secreted interferon act to effectively block replication of a broad spectrum of virus types, including HCMV. As such, the virus must exhibit counteractive mechanisms to these responses that involve their inhibition, tolerance, or re-purposing. The goal of this review is to describe the impact of the type I interferon system on HCMV replication and to showcase the number and diversity of strategies employed by the virus that allow infection of hosts in the presence of interferon-dependent activity.

  11. Cytomegalovirus Colitis in a Burn Patient.

    Science.gov (United States)

    Gibbs, Jeff T; Zieger, Madeline; Sood, Rajiv

    2016-01-01

    The prevalence of cytomegalovirus in the burn population is high. However, its role in the clinical management of burn patients is still being defined. This report documents a 41-year-old man who developed cytomegalovirus (CMV) colitis after being admitted with a 72% burn. Before the administration of ganciclovir, the authors had difficulty controlling his quantitative wound cultures with serial debridements, topical agents, and systemic antibiotics for known pathogens, which led to graft loss. After the ganciclovir was given, his quantitative wound cultures improved without changing the authors' topical agents or systemic antibiotics and had improved graft take. Whether CMV infection alone contributed to an increased morbidity in this patient or the combination of bacteria/fungal infection with CMV led to a synergistic effect is still not clearly understood. CMV may have contributed to a dysfunction in his cell mediated immunity, which, in turn, lowered the bacterial and fungal load necessary to cause graft loss. Patients who continue to do poorly despite adequate treatment for known pathogens may need to be screened for CMV and treated. PMID:26056763

  12. Prolonged activation of virus-specific CD8+T cells after acute B19 infection.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: Human parvovirus B19 (B19 is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously. METHODS AND FINDINGS: The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA-peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%-0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low. CONCLUSION: This is the first example to our knowledge of an "acute" human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation--analogous to that for cytomegalovirus infection--is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development.

  13. Cytomegalovirus Colitis and Subsequent New Diagnosis of Inflammatory Bowel Disease in an Immunocompetent Host: A Case Study and Literature Review

    Science.gov (United States)

    Khan, Tipu V.; Toms, Carla

    2016-01-01

    Patient: Male, 40 Final Diagnosis: CMV colitis Symptoms: Abdominal pain • diarrhea • jaundice Medication: — Clinical Procedure: Flexible sigmoidoscopy • colonoscopy Specialty: Family Medicine Objective: Rare co-existance of disease or pathology Background: Infection with gastrointestinal cytomegalovirus in an immunocompetent host is a rather rare occurrence in the literature. There are a few reports of gastrointestinal infection in the immunocompetent who are then subsequently given a new diagnosis of inflammatory bowel disease. It is speculated that the initial cytomegalovirus colitis infection triggers the onset of inflammatory bowel disease. Case Report: Herein we report a case of cytomegalovirus colitis and new diagnosis of inflammatory bowel disease identified in a 40-year-old immunocompetent adult man who presented with gastrointestinal symptoms and disseminated cytomegalovirus infection requiring anti-viral therapy, which successfully treated the episode of cytomegalovirus infection. He then went on to have persistent symptomatic inflammatory bowel disease confirmed by pathology. Conclusions: In this paper we will review the literature and explore the rare case of cytomegalovirus colitis in the immunocompetent host and discuss the pathology, physiology, diagnosis, and treatment of cytomegalovirus colitis. PMID:27460032

  14. 肾移植术后巨细胞感染对肾功能的影响%Effect of cytomegalovirus infection on long-term renal function after kidney transplantation

    Institute of Scientific and Technical Information of China (English)

    李丹

    2011-01-01

    OBJECTIVE To probe into the effect of long-term renal function of cytomegalovirus infection after kidney transplantation.METHODS A total of 86 cases of kidney transplantation patients after 6 months according to the provisions of the inspection, the antigenemia index was divided into four groups.Of the four groups after 6 months in patients with Cr and Ccr clearance rate, after 3 years, Ccr decreased rate of renal dysfunction on the incidence of renal transplant patients with TGF-β1mRNA and TGF-β1 protein expression were compared.RESULTS After renal transplantation in patients 6 months after the serum creatinine and ereatinine did not change significantly, there were not significant differences (P> 0.05).Engage in activities and long-term infection in renal transplant patients after 3 years the rate of decline in Ccr was only (4.39±3.67)ml/min, renal dysfunction rate was 42.86%, compared with the other groups were significantly lower; TGF allograft -βlmRNA relative content was 1.29±0.27, TGF-β1 protein expression was (12.69±2.17) ×106 which was significantly increased,there were also significant differences (P<0.05).CONCLUSION Active monitoring of CMV infection in the patients after renal transplantation is necessary, which can not only be used as a basis for treatment of patients but also effectively improve the long-term effects in patients with transplanted kidney.It is conducive to improv the quality of life in patients with very important clinical significance.%目的 探讨肾移植术后巨细胞感染对远期肾功能的影响.方法 选择2005年3月-2007年3月医院收治的同种异体肾移植术患者86例,依据术后<6个月所规定的检查中,抗原血症指数分为4组;对4组患者6个月后血肌酐(Cr)和肌酐清除率(Ccr)、术后<3年Ccr年下降速度及肾功能不全发生率、患者移植肾内TGF-β1mRNA和TGF-β1蛋白的表达情况进行比较分析.结果 患者肾移植术后6个月后血肌酐和肌酐变

  15. Integrin Activation and Viral Infection

    Institute of Scientific and Technical Information of China (English)

    Shan-dian GAO; Jun-zheng DU; Jian-hua ZHOU; Hui-yun CHANG; Qing-ge XIE

    2008-01-01

    Integrins are members of a ubiquitous membrane receptor family which includes 18 different α subunits and 8 β subunits forming more than 20 α/β heterodimers. Integrins play key functions in vascular endothelial cell and tumour cell adhesion, lymphocyte trafficking, tumor growth and viral infection. Current understanding of the molecular basis of integrins as viral receptors has been achieved through many decades of study into the biology of transmembrane glycoproteins and their interactions with several viruses. This review provides a summary of the current knowledge on the molecular bases of interactions between viruses and integrins, which are of potential practical significance. Inhibition of virus-integrin interactions at the points of virus attachment or entry will provide a novel approach for the therapeutic treatment of viral diseases.

  16. Activity of antiretroviral drugs in human infections by opportunistic agents

    Directory of Open Access Journals (Sweden)

    Izabel Galhardo Demarchi

    2012-03-01

    Full Text Available Highly active antiretroviral therapy (HAART is used in patients infected with HIV. This treatment has been shown to significantly decrease opportunist infections such as those caused by viruses, fungi and particularly, protozoa. The use of HAART in HIV-positive persons is associated with immune reconstitution as well as decreased prevalence of oral candidiasis and candidal carriage. Antiretroviral therapy benefits patients who are co-infected by the human immunodeficiency virus (HIV, human herpes virus 8 (HHV-8, Epstein-Barr virus, hepatitis B virus (HBV, parvovirus B19 and cytomegalovirus (CMV. HAART has also led to a significant reduction in the incidence, and the modification of characteristics, of bacteremia by etiological agents such as Staphylococcus aureus, coagulase negative staphylococcus, non-typhoid species of Salmonella, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. HAART can modify the natural history of cryptosporidiosis and microsporidiosis, and restore mucosal immunity, leading to the eradication of Cryptosporidium parvum. A similar restoration of immune response occurs in infections by Toxoplasma gondii. The decline in the incidence of visceral leishmaniasis/HIV co-infection can be observed after the introduction of protease inhibitor therapy. Current findings are highly relevant for clinical medicine and may serve to reduce the number of prescribed drugs thereby improving the quality of life of patients with opportunistic diseases.A terapia HAART (terapia antirretroviral altamente ativa é usada em pacientes infectados pelo vírus da imunodeficiência humana (HIV e demonstrou diminuição significativa de infecções oportunistas, tais como as causadas por vírus, fungos, protozoários e bactérias. O uso da HAART está associado com a reconstituição imunológica e diminuição na prevalência de candidíase oral. A terapia antirretroviral beneficia pacientes co-infectados pelo HIV, v

  17. Activity of andrographolide against chikungunya virus infection

    OpenAIRE

    Phitchayapak Wintachai; Parveen Kaur; Regina Ching Hua Lee; Suwipa Ramphan; Atichat Kuadkitkan; Nitwara Wikan; Sukathida Ubol; Sittiruk Roytrakul; Justin Jang Hann Chu; Smith, Duncan R.

    2015-01-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This stud...

  18. Analysis of haematological change in 56 infant cases infected with cytomegalovirus%巨细胞病毒感染患儿56例的血液学改变和临床分析

    Institute of Scientific and Technical Information of China (English)

    温晓梅

    2011-01-01

    目的 探讨巨细胞病毒感染对嬰幼儿血液系统的损害.方法 以ELISA法检测患儿血液CMV-IgM,对CMV-IgM阳性患儿并发血液系统损害的患儿进行回顾性分析.结果 在发生血液学改变的56例患儿中,轻度贫血42例,中度贫血14例,网织红细胞升高的27例(48%),血小板减少的23例(41%),白细胞升高的(>10×109/L)13例(23%),白细胞降低的(<4×109/L)12例(21%),外周血出现异型淋巴细胞的5例(9%).结论 血液系统损害是巨细胞病毒感染的症状之一,使用更昔洛韦抗病毒治疗,血液系统损害也随之好转.%Aim To analyzed the haematological change in 56 infant cases with cytomegalovirus (CMV) infection. Methods The CMV-IgM antibody in 56 infant cases infected CMV were detected with ELISA and the haematological change in 56 infant cases infected with CMV were analysed,retrospectively. Results Mild anemia occurred to 42 cases and moderate anemia occurred to 14 cases. Reticulated corpuscles was increased in 27 cases (48%),Platelet in 23 cases (41%)decreased,while white blood cell count in13 cases(23%) increased and reduced in 12 cases(21%). in addition,atypical lymphocytes in the peripheral blood were observed in 5 cases. Conclusions The damage ito the haematological system is one of the symptoms of CMV infection and the damage in the haematological system can be improved after antiviral treatment.

  19. Latent and Active Tuberculosis Infection Increase Immune Activation in Individuals Co-Infected with HIV

    Directory of Open Access Journals (Sweden)

    Zuri A. Sullivan

    2015-04-01

    Significance: Latent tuberculosis, which affects an estimated 1/3 of the world's population, has long been thought to be a relatively benign, quiescent state of M. tuberculosis infection. While HIV co-infection is known to exacerbate M. tuberculosis infection and increase the risk of developing active TB, little is known about the potential effect of latent TB infection on HIV disease. This study shows that HIV-infected individuals with both active and latent TB have elevated levels of inflammation and immune activation, biomarkers of HIV disease progression and elevated risk of mortality. These results suggest that, in the context of HIV, latent TB infection may be associated with increased risk of progression to AIDS and mortality.

  20. Cytomegalovirus-associated splenic infarcts in a female patient with Factor V Leiden mutation: a case report

    Science.gov (United States)

    Atzmony, Lihi; Saar, Nili; Chundadze, Tamar; Arbel, Yaron; Justo, Dan; Mashav, Noa

    2008-01-01

    Introduction Cytomegalovirus-associated thrombosis has rarely been reported in the medical literature, and if so, mainly in immunocompromized patients. Case presentation We report the case of a 36-year-old Caucasian woman with acute cytomegalovirus infection presenting with spontaneous splenic infarcts. Trans-esophageal echocardiography did not show any vegetations or mural thrombi. The patient was also found to be heterozygous for the Factor V Leiden mutation. Anticoagulation treatment was considered but ruled out since cytomegalovirus was the obvious trigger for thrombosis in this patient. To the best of our knowledge, this is only the third report to date of cytomegalovirus-associated splenic infarcts. Conclusion This case report serves as additional evidence for the role of cytomegalovirus in thrombosis. PMID:19087249

  1. Cytomegalovirus-associated splenic infarcts in a female patient with Factor V Leiden mutation: a case report

    Directory of Open Access Journals (Sweden)

    Atzmony Lihi

    2008-12-01

    Full Text Available Abstract Introduction Cytomegalovirus-associated thrombosis has rarely been reported in the medical literature, and if so, mainly in immunocompromized patients. Case presentation We report the case of a 36-year-old Caucasian woman with acute cytomegalovirus infection presenting with spontaneous splenic infarcts. Trans-esophageal echocardiography did not show any vegetations or mural thrombi. The patient was also found to be heterozygous for the Factor V Leiden mutation. Anticoagulation treatment was considered but ruled out since cytomegalovirus was the obvious trigger for thrombosis in this patient. To the best of our knowledge, this is only the third report to date of cytomegalovirus-associated splenic infarcts. Conclusion This case report serves as additional evidence for the role of cytomegalovirus in thrombosis.

  2. Antiviral treatment in patients with cytomegalovirus positive ulcerative colitis

    OpenAIRE

    Kadir OZTURK

    2014-01-01

    Cytomegalovirus (CMV) is a common virus in patients with ulcerative colitis receiving immunosuppressive drugs. Many studies suggested that CMV infection is an exacerbating factor in patients with ulcerative colitis. The role of CMV in exacerbations of ulcerative colitis has been discussed. One of studies starting this discussion is an article entitled “CMV positive ulcerative colitis: A single center experience and literature review” by Kopylov et al. However, we think that there are some poi...

  3. Is human cytomegalovirus associated with breast cancer progression?

    OpenAIRE

    Utrera-Barillas, Dolores; Valdez-Salazar, Hilda-Alicia; Gómez-Rangel, David; Alvarado-Cabrero, Isabel; Aguilera, Penélope; Gómez-Delgado, Alejandro; Ruiz-Tachiquin, Martha-Eugenia

    2013-01-01

    Background It has been hypothesized that human cytomegalovirus (HCMV) may be associated with breast cancer progression. However, the role of HCMV infection in breast cancer remains controversial. We aimed to assess whether HCMV genes (UL122 and UL83) could be detected in breast carcinomas and reinvestigated their possible association with breast cancer progression. DNA from paraffin-embedded tissues was analyzed by real-time PCR. We investigated 20 fibroadenomas and 27 primary breast carcinom...

  4. Cytomegalovirus and other herpesviruses infections in heart and bone marrow transplant recipients Infecções causadas por citomegalovírus e outros vírus do grupo herpes em transplantados cardíacos e de medula óssea

    OpenAIRE

    Adriana Weinberg; Lucy S. Vilas Boas; Olavo Feher; Tania M. V. Strabelli; Maria Cristina D. S. Fink; Frederico L. Dulley; Uip, David E.; Giovani Bellotti; Dalton A. F. Chamone; Vicente Amato Neto; Pannuti, Cláudio S.

    1990-01-01

    From January 1988 to January 1989 all the heart transplant and bone marrow recipients at the Instituto do Coração of the Hospital das Clínicas of the University of São Paulo Medical School were studied for the incidence and morbidity associated with herpesviruses infections after transplantation. Five bone marrow and 5 heart transplant recipients were followed for a mean of 4.2 months post-transplantation. All the patients were seropositive for cytomegalovirus (CMV) before admission and 80% e...

  5. Caprylic acid in the effective treatment of intractable medical problems of frequent urination, incontinence, chronic upper respiratory infection, root canalled tooth infection, ALS, etc., caused by asbestos & mixed infections of Candida albicans, Helicobacter pylori & cytomegalovirus with or without other microorganisms & mercury.

    Science.gov (United States)

    Omura, Yoshiaki; O'Young, Brian; Jones, Marilyn; Pallos, Andrew; Duvvi, Harsha; Shimotsuura, Yasuhiro

    2011-01-01

    There are many causes of frequent urination. Whenever water or fluids are consumed, the patient has to urinate within 10 or 20 min. Often urinary bladder examinations & blood tests show no significant abnormalities, & treatment by anti-bacterial or anti-viral agents does not improve the symptoms significantly. In intractable frequent urination with difficulty holding urine, as well as other intractable medical problems such as frequent coughing, white pus in gingiva, infection of the apex of a root canalled tooth, slow-healing wounds, & ALS, the authors often found coexisting mixed infections of Candida albicans (C.A.), Helicobacter pylori (H.P.), & Cytomegalovirus (CMV) with or without additional bacterial (Chlamydia trachomatis, etc.) or viral infections & increased Asbestos, with or without Hg deposits. We often found various degrees of mixed infections with C.A., H.P., & CMV in the external sphincters of the urethra & in the Trigone of the urinary bladder which consists of (1) a horizontal, band-like area between the 2 ureter openings & (2) the funnel shaped part of the Trigone at the lower half of the urinary bladder. In the coexistence of significant amounts of C.A., H.P. & CMV, the infection cannot be reduced by otherwise effective medicines for H.P. & CMV. However, one optimal dose of Diflucan, or Caprylic acid taken orally or externally applied, rapidly reduced the symptoms significantly. We found the best treatment is to give a combination of an optimal dose of Caprylic acid orally in the form of "CaprilyCare" or "Caprylic Acid," with a capsule of Omega-3 Fish Oil as an anti-viral agent, Amoxicillin, Substance Z & a Cilantro tablet. We found that an optimal dose of Caprylic acid increases normal cell telomere (NCT) to a desirable 750 ng BDORT units while Diflucan increases NCT by only 25 ng BDORT units, & with Omega-3 fish oil, leads to a mutual cancellation of both drugs. Thus, Caprylic acid is superior to & less expensive than Diflucan, & has potential

  6. 巨细胞病毒感染所致脑性瘫痪的临床特征%Analysis of the clinical characteristics of cerebral palsy caused by human cytomegalovirus infection

    Institute of Scientific and Technical Information of China (English)

    陈星; 陈见南; 杨路; 陈春花; 邱纪方

    2015-01-01

    Objective To Analyze the clinical characteristics of cerebral palsy caused by human cytomegalovirus (CMV) infection.Methods Fifty-one cases of CMV infection were studied by analyzeing related clinical symptoms of cerebral palsy,finding its characteristics,and analyzing its causes by comparing with control group of 50 patients with cerebral palsy caused by other etiologies.Results The clinical symptoms of cerebral palsy caused by CMV infection were similar to those of cerebral palsy caused by other etiologies,however,the clinical symptoms of cerebral palsy caused by other reasons were more severe; 37.25% of cases with cerebral palsy caused by CMV infection showed damage to liver function.Developmental quotient determination of cerebral palsy caused by CMV infection was 90.20% which was moderate to severe,whereas that of 52.6% of cases with cerbral palsy caused by other causes were moderate to severe.There was a significant difference between the two groups with respect to their developmental quotient.The motor function in 88.23% of patients with cerebral palsy caused by human CMV infection was class Ⅱ-Ⅲ,which was mainly in mild to moderate damage.Conclusions The motor function of cerebral palsy caused by CMV was mostly in the slight to moderat damage,however the mental development obviously was mostly in moderate to severe defects,which showed that the mental damage was much greater than the motor function damage.In patients with cerebral palsy caused by other causes,the degree of motor function damage was higher than the degree of intelligence damage.Besides,the children with cerebral palsy caused by CMV infection were easy to suffer multiple organ injury such as liver damage.%目的 对临床证实由巨细胞病毒(CMV)感染所致的脑性瘫痪的患儿进行临床特点分析.方法 对51例明确由CMV感染的脑性瘫痪进行相关临床症状分析,找出其特性,并分析其发生的原因.结果 在CMV感染所致的脑性瘫痪的临床

  7. [Associated infections in acute bronchopulmonary infections in children].

    Science.gov (United States)

    Lykova, E A; Vorob'ev, A A; Bokovoĭ, A G; Karazhas, N V; Evseeva, L F

    2003-01-01

    A total of 189 children with bacterial complications of the acute respiratory viral infection (ARVI)--primarily with pneumonia and bronchitis--were dynamically examined for typical and atypical pneumotropic causative agents of the infection process (Mycoplasma pneumoniae, Chlamydia spp., Streptococcus pneumoniae, Haemophilus influenzae, Pneumocystis carini, and Citomegalovirus). A high frequency rate of the associative infection involving mycoplasmas and pneumocysts was registered (45-50%); it was lower in the cases involving Chlamydias, hemophilic bacteria, pneumococcus, and cytomegalovirus--up to 25-30%. No sharp difference was found between the indices of an infection degree and those of an active clinical infectious process involving the same pneumotropic agent: the biggest difference was observed in Chlamydia infections (9.4%) and the lowest one--in mycoplasma infections (3%). A dynamic comparison of different classes of immunoglobulins revealed that, in acute bronchitis and pneumonias, the Chlamydia and cytomegalovirus infections are, primarily, of the persistent nature; the hemophilic and pneumocystic infections are of a mixed nature; and the pneumococcus one is of the acute nature. The Mycoplasma infection, which is more often encountered in pre-school children, is of the primary type with a trend towards a prolonged clinical course. All pneumonias had a typical clinical course; the clinical picture was compared in 128 patients with the etiological factor (including a description of characteristic symptoms). PMID:12861708

  8. Can chemoprophylaxis against opportunistic infections be discontinued after an increase in CD4 cells induced by highly active antiretroviral therapy?

    DEFF Research Database (Denmark)

    Kirk, O; Lundgren, Jens Dilling; Pedersen, C;

    1999-01-01

    /100 PY follow-up (95% confidence interval, 0.0-3.2). No cases of cerebral toxoplasmosis, cytomegalovirus chorioretinitis, or disseminated Mycobacterium avium infection were observed. Follow-up time for these was, however, limited. CONCLUSION: PCP-chemoprophylaxis can be safely discontinued after HAART...

  9. Comparison of serology, antigenemia assay and the polymerase chain reaction for monitoring active cytomegalovirus infections in hematopoietic stem cell transplantation patients Estudo comparativo entre sorologia, antigenemia e reação em cadeia da polimerase para o monitoramento da infecção por citomegalovírus em pacientes receptores de transplantes de células progenitoras hematopoéticas

    Directory of Open Access Journals (Sweden)

    Sandra Helena Alves Bonon

    2006-10-01

    Full Text Available Forty-six allogeneic hematopoietic stem cell transplantation (HSCT patients were monitored for the presence of CMV antibodies, CMV-DNA and CMV antigens after transplantation. Immunoenzymatic serological tests were used to detect IgM and the increase in CMV IgG antibodies (increase IgG, a nested polymerase chain reaction (N-PCR was used to detect CMV-DNA, and an antigenemia assay (AGM was used to detect CMV antigens. The presence of CMV-IgM and/or CMV-increase IgG antibodies was detected in 12/46 (26.1% patients, with a median time between HSCT and the detection of positive serology of 81.5 days. A positive AGM was detected in 24/46 (52.2% patients, with a median time between HSCT and antigen detection of 62 days. Two or more consecutive positive N-PCR results were detected in 32/46 (69.5% patients, with a median time between HSCT and the first positive PCR of 50.5 days. These results confirmed that AGM and mainly PCR are superior to serology for the early diagnosis of CMV infection. Six patients had CMV-IgM and/or CMV-increase IgG with a negative AGM (five cases or N-PCR assay (one case. In five of these cases the serological markers were detected during the first 100 days after HSCT, the period of highest risk. These findings support the idea that serology may be useful for monitoring CMV infections in HSCT patients, especially when PCR is unavailable.Quarenta e seis pacientes receptores de transplantes de células progenitoras hematopoéticas (TCPH foram monitorados em relação à infecção ativa por citomegalovírus (CMV. Testes sorológicos imunoenzimáticos foram utilizados para a detecção de anticorpos IgM e elevação significativa das concentrações de anticorpos IgG (aumento IgG, nested-PCR (N-PCR foi utilizada para a detecção de CMV-DNA e antigenemia (AGM para a detecção de antígenos virais. A presença de CMV-IgM e/ou CMV-aumento IgG foi detectada em 12/46 (26,1% pacientes, sendo o tempo mediano entre o transplante e a detec

  10. Activity of andrographolide against chikungunya virus infection.

    Science.gov (United States)

    Wintachai, Phitchayapak; Kaur, Parveen; Lee, Regina Ching Hua; Ramphan, Suwipa; Kuadkitkan, Atichat; Wikan, Nitwara; Ubol, Sukathida; Roytrakul, Sittiruk; Chu, Justin Jang Hann; Smith, Duncan R

    2015-01-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent. PMID:26384169

  11. Effects of Various Prophylactic Solutions on Postoperative Cytomegalovirus Infection in Liver Transplant Recipients%不同预防方案对肝移植受者术后巨细胞病毒感染率的影响

    Institute of Scientific and Technical Information of China (English)

    王葆青; 张洁; 张含之; 周俭; 何礼贤

    2013-01-01

    Objective:To investigate the status of postoperative cytomegalovirus (CMV) infection among the liver transplant recipients and to evaluate the effects of prophylactic solutions on CMV infection after liver transplantation in China.Methods:All the clinical and follow-up data was retrospectively investigated in 309 liver transplantation patients from January 2004 to March 2007 in Liver Transplantation Center,Zhongshan Hospital,Fudan university.Results:In the preoperative CMV-seropositive recipients,the CMV infection rates in the three prophylactic groups (PG group) who have been treated with intravenous ganciclovir (GCV),acyclovir (ACV),GCV + ACV were 10.5 %,15.9% and 7.9 %,respectively.The incidences of the CMV disease were 10.5%,8.3% and 3.2%,which showed significant differences compared to those in the non-prophylactic group (NPG group,42.3% and 15.4%,P<0.01).One-year overall survival rates of the three PG groups were 86.8%,78.0% and 88.9%,respectively.There was statistical difference in one-year survival rate between GCV+ ACV group and the NPG group (P<0.05).Conclusions:In the preoperative CMV-seropositive recipients,all the three different prophylactic methods [GCV 2.5 mg/(kg · d) ; ACV (0.2 g); and GCV 2.5 mg/(kg · d) + ACV 0.2 mg/(kg · d),3 times perday] can lower the incidence of CMV infection and CMV disease.Moreover,GCV + ACV prophylactic treatment can significantly increase one-year survival rate of liver transplantation patients.%目的:了解肝移植受者术后巨细胞病毒(cytomegalovirus,CMV)感染情况,探讨预防方案对肝移植受者术后CMV感染的预防作用.方法:回顾分析复旦大学附属中山医院肝移植中心2004年1月-2007年3月309例肝移植患者术后1年内的临床资料.结果:术前受体CMV-IgG阳性的肝移植患者中,3个预防组(PG组)分别采用更昔洛韦(ganciclovir,GCV)、阿昔洛韦(acyclovir,ACV)和GCV+ ACV预防后,CMV隐性感染发生率分别为10.5%、15.9

  12. Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.

    Science.gov (United States)

    Pérez, J L

    1997-09-01

    Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.

  13. Activated iNKT cells promote memory CD8+ T cell differentiation during viral infection.

    Directory of Open Access Journals (Sweden)

    Emma C Reilly

    Full Text Available α-Galactosylceramide (α-GalCer is the prototypical lipid ligand for invariant NKT cells. Recent studies have proposed that α-GalCer is an effective adjuvant in vaccination against a range of immune challenges, however its mechanism of action has not been completely elucidated. A variety of delivery methods have been examined including pulsing dendritic cells with α-GalCer to optimize the potential of α-GalCer. These methods are currently being used in a variety of clinical trials in patients with advanced cancer but cannot be used in the context of vaccine development against pathogens due to their complexity. Using a simple delivery method, we evaluated α-GalCer adjuvant properties, using the mouse model for cytomegalovirus (MCMV. We measured several key parameters of the immune response to MCMV, including inflammation, effector, and central memory CD8(+ T cell responses. We found that α-GalCer injection at the time of the infection decreases viral titers, alters the kinetics of the inflammatory response, and promotes both increased frequencies and numbers of virus-specific memory CD8(+ T cells. Overall, our data suggest that iNKT cell activation by α-GalCer promotes the development of long-term protective immunity through increased fitness of central memory CD8(+ T cells, as a consequence of reduced inflammation.

  14. Cytomegalovirus ileitis in an immunocompetent elderly adult

    Institute of Scientific and Technical Information of China (English)

    Kum Hei Ryu; Sun Young Yi

    2006-01-01

    Cytomegalovirus enteritis is most usually associated with patients positive for human immunodeficiency virus or immunosuppressed transplant patients. The gastrointestinal tract may be affected anywhere from the esophagus to the colon, but the small bowel involvement is rare. We report a case of cytomegalovirus ileitis in an immunocompetent adult, which was confirmed by histopathologic findings through colonoscopic biopsy.

  15. The relationship between expressions of C-type lectin receptors on natural killer cells and infant human cytomegalovirus infection%婴儿巨细胞病毒感染与自然杀伤细胞C型凝集素受体的表达

    Institute of Scientific and Technical Information of China (English)

    郭红梅; 李玫; 林谦; 张兰芳

    2010-01-01

    目的 探讨自然杀伤(NK)细胞C型凝集素受体表达与婴儿人巨细胞病毒(HCMV)感染的关系.方法 2006年1月至2008年6月HCMV感染患儿79例和母乳性黄疸对照患儿39例.根据外周血中性粒细胞pp65抗原血症结果,分为活动性HCMV感染组48例和非活动性HCMV感染组31例,并对活动性HCMV感染组的48例婴儿进行更昔洛韦治疗2周.应用流式细胞术检测外周血NK细胞C型凝集素受体NKG2A、NKG2C、NKG2D表达.三组数据比较采用Kruskal-Wallis独立样本非参数检验,两组之间比较采用Mann-Whiteney配对样本非参数检验.结果 NK细胞抑制性受体NKG2A表达在活动性HCMV感染组、非活动性HCMV感染组和对照组之间差异无统计学意义(x2=3.95,P>0.05);NK细胞活化性受体NKG2C、NKG2D表达在活动性HCMV感染组、非活动性HCMV感染组和对照组之间差异有统计学意义(x2=24.91,P<0.01;x2=47.80,P<0.01).NK细胞活化性受体NKG2C、NKG2D表达在HCMV感染组较对照组明显升高(Z=-4.72,P<0.01;Z=-5.15,P<0.01).NK细胞活化性受体NKG2D表达在活动性HCMV感染组较非活动性HCMV感染组明显升高(Z=-5.08,P<0.01).更昔洛韦治疗后NK细胞活化性受体NKG2D表达降低(Z=-1.34,P=0.07).结论 在调节NK细胞功能和婴儿抗HCMV免疫方面,NKG2C和NKG2D表达可能起重要作用.%Objective To explore the relationship between expressions of C-type lectin receptors on natural killer(NK) cells and infant human cytomegalovirus (HCMV) infection. Methods Seventynine cases of HCMV infection infants and 39 cases of HCMV non-infection control infants admitted during January 2006 to June 2008 were recruited in this study. According to HCMV pp65 antigenemia levels in the peripheral blood, 79 cases of HCMV infection infants were divided into two groups: 48cases of active HCMV infection and 31 cases of inactive HCMV infection. The 48 cases of infants with active HCMV infection were treated with ganciclovir for 2 weeks. The

  16. Cytomegalovirus and other herpesviruses infections in heart and bone marrow transplant recipients Infecções causadas por citomegalovírus e outros vírus do grupo herpes em transplantados cardíacos e de medula óssea

    Directory of Open Access Journals (Sweden)

    Adriana Weinberg

    1990-10-01

    Full Text Available From January 1988 to January 1989 all the heart transplant and bone marrow recipients at the Instituto do Coração of the Hospital das Clínicas of the University of São Paulo Medical School were studied for the incidence and morbidity associated with herpesviruses infections after transplantation. Five bone marrow and 5 heart transplant recipients were followed for a mean of 4.2 months post-transplantation. All the patients were seropositive for cytomegalovirus (CMV before admission and 80% experienced one or more recurrences during the observation period. Of the 12 episodes of CMV infection, that were identified in this study, 83% were accompanied by clinical or laboratory abnormalities. However, there was only one case of severe disease. The overall incidence of infection for herpes simplex (HSV was 50%. Although most of HSV reactivations were oral or genital, one case of HSV hepatitis occurred. One of the 6 episodes of HSV infections that were treated with acyclovir showed an unsatisfactory response and was successfully managed with ganciclovir. All the individuals had anti-varicella zoster virus antibodies, but none of them developed infection. The study emphasizes the importance of active diagnostic surveillance of herpesvirus infections in transplant patients. Both CMV and HSV reactivations showed high incidence and important morbidity and thus, deserve prophylactic therapy.De janeiro de 1988 a janeiro de 1989 todos os pacientes submetidos a transplante de coração ou de medula óssea no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foram estudados quanto à incidência e morbidade das infecções pós-transplante causadas por vírus do grupo herpes. Cinco recipientes de medula óssea e 5 transplantados cardíacos foram observados por um período médio de 4.2 meses após o transplante. Todos os pacientes tinham sorologia positiva para citomegalovírus (CMV antes do transplante

  17. 先天性HCMV感染胎鼠大脑皮层ET-1 mRNA的研究%Study on endothelin-1 mRNA of cerebral cortex of fetal mouse following congenital human cytomegalovirus infection

    Institute of Scientific and Technical Information of China (English)

    袁中玉; 王明丽; 陈贵海; 李京培

    2001-01-01

    目的 对先天性人巨细胞病毒(HCMV)感染的胎鼠大脑皮层内皮素-1(ET-1)mRNA进行测定,以探讨先天性HCMV感染致脑损害的机制。方法 在建立先天性HCMV中枢神经系统(CNS)感染胎鼠模型的基础上,用逆转录-聚合酶链式反应(RT-PCR)测定受不同病毒剂量感染的胎鼠大脑皮层ET-1mRNA,并用地高辛标记的ET-1寡核苷酸探针对大脑皮层细胞印片进行原位杂交以检测相应mRNA转录量及胞内定位。结果 在大脑皮层组织的上清液中HCMV分离阳性;病理学研究证实受染胎鼠大脑皮层表现为侵袭性脑膜脑炎性改变,并在神经细胞内发现特异性核内嗜碱性包涵体。RT-PCR和原位杂交研究发现,受染胎鼠大脑皮层内ET-1mRNA转录量增加,以1.0ml和0.5ml组为显著,而0.25ml组与正常对照组比较无明显差别。结论 HCMV可经胎盘垂直传播至胎鼠脑组织。先天性HCMV感染可刺激受染胎鼠CNSET-1mRNA的转录,且与母鼠所接种的病毒量存在一定的量效关系。这些结果提示,ET-1在先天性HCMV感染脑损害过程中,早期可导致组织缺血性改变,而晚期则与受损大脑皮层的功能恢复有关。这对了解先天性HCMV感染致CNS损伤的机理将提供有价值的参考依据,同时也为临床防治和优生优育提供一种有价值的手段。%Objective To explore mechanisms of brain damage followingcongenitally infected human cytomegalovirus, the transcription of endothelin-1 (ET-1) mRNA of fetal mouse cerebral cortex (HCMV) were analyzed. Methods On the basis of developing congenital HCMV infective fetal model, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine ET-1 mRNA of fetal mouse cerebral cortex infected by different inoculum size meanwhile the intracellular location of mRNA's was conducted with in situ hybridization by digoxigenin labelled ET-1 mRNA oligonucleotide probe. Virus isolation and sections coated

  18. Cytomegalovirus replicon-based regulation of gene expression in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Hermine Mohr

    Full Text Available There is increasing evidence for a connection between DNA replication and the expression of adjacent genes. Therefore, this study addressed the question of whether a herpesvirus origin of replication can be used to activate or increase the expression of adjacent genes. Cell lines carrying an episomal vector, in which reporter genes are linked to the murine cytomegalovirus (MCMV origin of lytic replication (oriLyt, were constructed. Reporter gene expression was silenced by a histone-deacetylase-dependent mechanism, but was resolved upon lytic infection with MCMV. Replication of the episome was observed subsequent to infection, leading to the induction of gene expression by more than 1000-fold. oriLyt-based regulation thus provided a unique opportunity for virus-induced conditional gene expression without the need for an additional induction mechanism. This principle was exploited to show effective late trans-complementation of the toxic viral protein M50 and the glycoprotein gO of MCMV. Moreover, the application of this principle for intracellular immunization against herpesvirus infection was demonstrated. The results of the present study show that viral infection specifically activated the expression of a dominant-negative transgene, which inhibited viral growth. This conditional system was operative in explant cultures of transgenic mice, but not in vivo. Several applications are discussed.

  19. Comparative magnitude and kinetics of human cytomegalovirus-specific CD4(+) and CD8(+) T-cell responses in pregnant women with primary versus remote infection and in transmitting versus non-transmitting mothers: Its utility for dating primary infection in pregnancy.

    Science.gov (United States)

    Fornara, Chiara; Furione, Milena; Arossa, Alessia; Gerna, Giuseppe; Lilleri, Daniele

    2016-07-01

    To discriminate between primary (PI) and remote (RI) human cytomegalovirus (HCMV) infection, several immunological parameters were monitored for a 2-year period in 53 pregnant women with PI, and 33 pregnant women experiencing HCMV PI at least 5 years prior. Cytokine (IFN-γ and IL-2) production by and phenotype (effector/memory CD45RA(+) ) of HCMV-specific CD4(+) and CD8(+) T-cells as well as the lymphoproliferative responses (LPR) were evaluated, with special reference to the comparison between a group of women transmitting (T) and a group of non-transmitting (NT) the infection to fetus. While HCMV-specific CD4(+) T-cells reached at 90 days post-infection (p.i.) values comparable to RI, CD8(+) T-cells reached at 60 days p.i. levels significantly higher and persisting throughout the entire follow-up. Instead, IL-2 production and lymphoproliferative responses were lower in PI than RI for the entire follow-up period. Effector memory CD45RA(+) CD4(+) and CD8(+) HCMV-specific T-cells increased until 90 days p.i., reaching and maintaining levels higher than RI. The comparison between T and NT women showed that, at 30 days p.i., in NT women there was a significantly higher IL-2 production by HCMV-specific CD4(+) T-cells, and at 60 days p.i. a significantly higher frequency of both specific CD4(+) and CD8(+) CD45RA(+) T-cells. HCMV T-cell response appears to correlate with virus transmission to fetus and some parameters (CD4(+) lymphoproliferation, and frequency of HCMV-specific CD8(+) IL2(+) T-cells) may help in dating PI during pregnancy. J. Med. Virol. 88:1238-1246, 2016. © 2015 Wiley Periodicals, Inc. PMID:26680747

  20. Role of Peritoneal Macrophages in Cytomegalovirus-induced Acceleration of Autoimmune Diabetes in BB-rats

    Directory of Open Access Journals (Sweden)

    Jan-Luuk Hillebrands

    2003-01-01

    Full Text Available Background: As one of the natural perturbants, infection with cytomegalovirus (CMV is believed to play a role in the development of Type I diabetes. Using the DP-BB rat model for autoimmune diabetes, we here report about possible mechanisms responsible for R(atCMV-induced accelerated onset of diabetes.

  1. A case of invasive cytomegalovirus duodenitis in an immunosuppressed patient 15 months after renal transplantation.

    Science.gov (United States)

    Kazanji, N; Davila, F; Manickam, P; Wang, Y; Bossory, L

    2015-06-01

    Cytomegalovirus (CMV) remains one of the most important infections in kidney transplantation. Only a handful of images have been reported in the literature thus far. We present classic pathologic and gross images of CMV duodenitis in an immunosuppressed patient more than one year post-renal transplantation. PMID:25582982

  2. Child Care Provider Awareness and Prevention of Cytomegalovirus and Other Infectious Diseases

    Science.gov (United States)

    Thackeray, Rosemary; Magnusson, Brianna M.

    2016-01-01

    Background: Child care facilities are prime locations for the transmission of infectious and communicable diseases. Children and child care providers are at high risk for cytomegalovirus (CMV) infection which causes severe birth defects and developmental delays. Objective: The goals of study were: (1) to determine the level of cytomegalovirus…

  3. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis.

    Science.gov (United States)

    Tan, Susanna K; Burgener, Elizabeth B; Waggoner, Jesse J; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F; Pinsky, Benjamin A

    2016-01-01

    Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P comprehensive definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis. PMID:26885542

  4. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis.

    Science.gov (United States)

    Tan, Susanna K; Burgener, Elizabeth B; Waggoner, Jesse J; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F; Pinsky, Benjamin A

    2016-01-01

    Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

  5. 婴幼儿巨细胞病毒感染138例临床及治疗观察%Clinical characteristics and therapy of cytomegalovirus infection in 138 infant cases

    Institute of Scientific and Technical Information of China (English)

    徐玉敏; 朱雪萍; 肖志辉; 丁晓春; 冯星

    2013-01-01

    目的:探讨婴幼儿巨细胞病毒( CMV)感染的临床特点及治疗。方法:对在我院确诊、住院治疗的138例CMV感染患儿的临床资料进行回顾性分析。结果:138例患儿(男80例,女58例)血清CMV-IgM阳性和(或)血、尿CMV-DNA-PCR阳性,入院年龄9 d~3岁。临床表现为肺炎99例,伴有肺功能改变18例;婴儿肝炎62例,其中肝硬化1例,肝豆状核变性1例,高胆红素血症30例(2例合并核黄疸,3例胆道闭锁,1例胆总管囊肿,3例肝糖原累积症);溶血性贫血10例,特发性血小板减少症6例;脑发育异常15例,其中脑积水1例、脑结节硬化2例、运动落后3例、智力低下3例、癫痫2例;脑干听觉诱发电位异常16例(双侧听力受损10例、青光眼1例);先天性心脏病8例,多发畸形3例,迁延性肠炎5例,营养不良7例,喉软骨发育不良3例,选择性IgA缺乏症1例,遗传代谢性疾病1例,同时合并多重感染11例,合并呼吸衰竭、休克2例。治疗后好转114例,放弃治疗19例,死亡5例。结论:婴幼儿CMV感染临床表现多样化,以肺炎最多见;其次是肝胆系统受累。中枢神经系统受损可导致脑发育异常、听神经受损、运动落后等,少数病例可伴发其他畸形甚至多发畸形。绝大部分CMV感染病例预后良好,少数病例预后差甚至死亡。%Objective:To investigate the clinical characteristics and therapy of cytomegalovirus ( CMV) infection in infants.Methods:Clinical characteristics and outcome were retrospectively analyzied of in 138 infants infected CMV diagnosed in our hospital.Results:One hundred thirty-eight cases(male 80, female 58) were diagnosed by the positive of serum CMV-IgM and or blood/urine CMV-DNA-PCR.The admission age was 9 d to 3-year-old. Ninety-nine patients were diagnosed as pneumonia , 18 showed lung function detects .Sixty-two cases were diagnosed as infant hepatitis , 1

  6. Active Epstein-Barr virus infection after allogeneic stem cell transplantation : re-infection or reactivation?

    NARCIS (Netherlands)

    Meijer, E; Spijkers, S; Moschatsis, S; Boland, GJ; Thijsen, SFT; van Loon, AM; Verdonck, LF

    2005-01-01

    Recipients of allogeneic stem cell transplants (SCT) often show active Epstein-Barr virus (EBV) infection, which may progress to EBV-associated lymphoproliferative disorders. It is not known whether these EBV infections are true reactivations of the endogenous EBV strain or re-infections with an exo

  7. Progresses in diagnosis and treatment of intrauterine infection with cytomegalovirus and human parvovirus B19%巨细胞病毒和人细小病毒B19宫内感染的诊治进展

    Institute of Scientific and Technical Information of China (English)

    吴婉芳

    2003-01-01

    @@ 近20年来,国内外学者对TORCH感染做了大量工作,取得了很大的成绩.但也还有许多尚未解决的问题.现仅就巨细胞病毒(cytomegalovirus, CMV)和人细小病毒B19(human parvovirus B19,HPV B19)宫内感染的某些方面,提出以下意见供同道参考.

  8. Effect of desferrioxamine (DFO) and calcium trinatrium diethylenetriaminepentaacetic acid (DTPA) on rat cytomegalovirus replication in vitro and in vivo.

    Science.gov (United States)

    Kloover, J S; Scholz, M; Cinatl, J; Lautenschlager, I; Grauls, G E; Bruggeman, C A

    1999-11-01

    Cytomegalovirus (CMV) infection is a major problem in the immunosuppressed patient. It is thought that besides direct CMV induced cell lysis, immunological damage is part of CMV pathogenesis. New antiviral drugs, which combine immunomodulating and antiviral qualities, could be beneficial. Recently, it has been described that desferrioxamine (DFO) and calcium trinatrium diethylenetriaminepentaacetic acid (DTPA) exhibit both properties. In this report the antiviral effects of both compounds against rat CMV (RCMV) are described in vitro and in vivo using a generalised and local infection model. In vitro, both compounds exhibited a significant antiviral effect, DTPA being more potent than DFO. However, in the generalised infection model no effect was seen on mortality, morbidity or presence of virus in internal organs. In rats infected subcutaneously in the hind paw, no effect was seen locally on paw thickness, presence of viral antigens and inflammatory response. In addition, these rats suffered from a generalised infection of low magnitude at 15 days post infection, although both DFO and DTPA were able to lower the level of viral replication. In conclusion, our data indicate that despite in vitro activity, in vivo usage of DFO or DTPA for acute CMV infection is not warranted.

  9. STUDIES OF LYMPHOCYTE SUBSETS IN PATIENTS WITH A MIXED INFECTION CAUSED BY THE VIRUSES FROM HERPESVIRIDAE FAMILY

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    T. I. Dolgikh

    2010-01-01

    Full Text Available Present work deals with specific immunologic changes that are typical to various types of mixed infection caused by viruses from Herpesviridae family during their activation phase. These changes include increased amounts of CD3+/CD25+ lymphocytes and CD3+/CD4+ cells, decreased levels of CD3+/CD95+ cells, increased contents of natural killer cells, altered interrelations between the immune system parameters. Involvement of cytomegalovirus or Epstein-Barr virus (EBV in the mixed infection is associated with some special changes of the lymphocyte subsets. I.e., a co-infection with herpes virus simplex (HSV type 1/2 and cytomegalovirus is characterized by increased amounts of activated T-lymphocytes and T-helper cells, whereas mixed HSV/EBV infection is accompanied by sharp reduction in CD3+/CD95+ lymphocytes.

  10. Cytomegalovirus implicated in a case of progressive outer retinal necrosis (PORN).

    Science.gov (United States)

    Sfeir, Maroun

    2015-08-01

    Progressive outer retinal necrosis, also known as PORN, has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with acquired immune deficiency syndrome (AIDS). Although the etiologic organism has been reported to be Varicella-zoster virus, cytomegalovirus (CMV) can be an etiologic agent. Our case illustrates the occurrence of two opportunistic infections: PORN associated with CMV and Mycobacterium avium intracellulare duodenitis in a patient with uncontrolled HIV infection.

  11. Cytomegalovirus implicated in a case of progressive outer retinal necrosis (PORN).

    Science.gov (United States)

    Sfeir, Maroun

    2015-08-01

    Progressive outer retinal necrosis, also known as PORN, has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with acquired immune deficiency syndrome (AIDS). Although the etiologic organism has been reported to be Varicella-zoster virus, cytomegalovirus (CMV) can be an etiologic agent. Our case illustrates the occurrence of two opportunistic infections: PORN associated with CMV and Mycobacterium avium intracellulare duodenitis in a patient with uncontrolled HIV infection. PMID:26209386

  12. Cytomegalovirus-induced embryopathology: mouse submandibular salivary gland epithelial-mesenchymal ontogeny as a model

    Directory of Open Access Journals (Sweden)

    Huang Jing

    2006-09-01

    Full Text Available Abstract Background Human studies suggest, and mouse models clearly demonstrate, that cytomegalovirus (CMV is dysmorphic to early organ and tissue development. CMV has a particular tropism for embryonic salivary gland and other head mesenchyme. CMV has evolved to co-opt cell signaling networks so to optimize replication and survival, to the detriment of infected tissues. It has been postulated that mesenchymal infection is the critical step in disrupting organogenesis. If so, organogenesis dependent on epithelial-mesenchymal interactions would be particularly vulnerable. In this study, we chose to model the vulnerability by investigating the cell and molecular pathogenesis of CMV infected mouse embryonic submandibular salivary glands (SMGs. Results We infected E15 SMG explants with mouse CMV (mCMV. Active infection for up to 12 days in vitro results in a remarkable cell and molecular pathology characterized by atypical ductal epithelial hyperplasia, apparent epitheliomesenchymal transformation, oncocytic-like stromal metaplasia, β-catenin nuclear localization, and upregulation of Nfkb2, Relb, Il6, Stat3, and Cox2. Rescue with an antiviral nucleoside analogue indicates that mCMV replication is necessary to initiate and maintain SMG dysmorphogenesis. Conclusion mCMV infection of embryonic mouse explants results in dysplasia, metaplasia, and, possibly, anaplasia. The molecular pathogenesis appears to center around the activation of canonical and, perhaps more importantly, noncanonical NFκB. Further, COX-2 and IL-6 are important downstream effectors of embryopathology. At the cellular level, there appears to be a consequential interplay between the transformed SMG cells and the surrounding extracellular matrix, resulting in the nuclear translocation of β-catenin. From these studies, a tentative framework has emerged within which additional studies may be planned and performed.

  13. Human cytomegalovirus UL144 open reading frame: sequence variability in Guangzhou congenital infected children%广州地区HCMV临床病毒株UL144 ORF的序列变异研究

    Institute of Scientific and Technical Information of China (English)

    王波; 李月琴; 叶宁; 胡兢晶; 何震宇; 田传军; 张纯青; 叶铁真; 周天鸿

    2008-01-01

    目的 研究广州地区先天性感染的人巨细胞病毒(HCMV)临床低传代分离病毒株UL144基因序列的多态性,探讨UL144基因在HCMV致病中的作用.方法 对3株经多重PCR鉴定HCMV DNA为阳性的临床低传代分离株进行HCMV UL144基因全序列PCR扩增,PCR产物克隆到pMD18-T载体上再测序,将其序列与GenBank中公布的其它10株临床分离株UL144基因一起进行分析.结果 本实验克隆并测序了HCMV临床低传代D3、D2和D52病毒株的UL144基因,提交GenBank,已被GenBank收录,序列号分别为DQ180368、DQ180382和DQ180355.HCMV临床低传代D3、D2和D52病毒株的UL144基因均全长531 bp.通过blast分析,从GenBank中找到了10株HCMV病毒株的UL144与D3、D2和D52的UL144基因具有较高的同源性,经过序列的比对,发现UL144基因DNA序列比较保守,只在4处有变异,且变异均为碱基替换,无插入或缺失,编码蛋白由176个氨基酸残基组成,氨基酸序列也比较保守,各分离株中变异率为1.1%;HCMV UL144编码蛋白翻译后修饰位点在所有分离株中均高度保守;所有分离株UL144蛋白的等电点均为8.97.结论 广州地区临床低传代分离株HCMV UL144基因DNA及其编码产物的氨基酸序列是比较保守的,但仍存在一定的多态性.提示UL144基因在先天性感染中可能具有重要作用.%Objective To investigate the polymorphism of human cytomegalovirus (HCMV) UL144 gene of the low passage clinical isolates in Guangzhou and explore the role of UL144 gene in HCMV pathogenicity. Methods The clinical isolates of HCMV were obtained from the urine sample collected from those infants with intra-uterus HCMV infection in Guangzhou. The virus genome DNA was extracted. According to the genome sequence of Toledo, primers for UL144 gene were designed and used to amplify the complete open reading frames (ORF) of the UL144 gene in our 3 different clinical isolates. These ORFs of the UL144 gene were cloned into pMD18-T vector

  14. 温州市区育龄妇女孕前巨细胞病毒感染现状调查%Investigation of human cytomegalovirus infection among women before pregnancy in Wenzhou region

    Institute of Scientific and Technical Information of China (English)

    吕静娟; 胡文胜; 余坚; 郑晓群

    2011-01-01

    目的 了解温州地区育龄妇女孕前人巨细胞病毒(HCMV)感染的状况.方法 收集2008年10月至2010年6日参加温州市龙湾区免费孕前优生筛查的妇女血标本2869份,采用酶联免疫吸附试验(ELISA)检测血清HCMV IgG/IgM抗体;HCMV IgM抗体阳性标本,采用实时荧光定量聚合酶链反应(FQ-PCR)检测血HCMV DNA载量;HCMV IgG/IgM抗体双阳性标本,采用尿素变性结合ELISA技术检测IgG抗体亲和力指教(AI).结果 2869份孕前妇女血清中HC-MV IgG抗体阳性检出率为97.77%(2805/2869),HCMV IgM抗体阳性检出率为0.77%(22/2 869),IgG/IgM抗体均阳性检出率占0.17%(5/2 869);22份HCMV IgM阳性标本中,血HCMV DNA阳性检出率为68.18%(15/22);5份HCMVIgG/IgM双阳性标本中,检出低亲和力IgG抗体1份,中等亲和力IgG抗体2份,高亲和力IgG抗体2份.结论 温州市区育龄妇女孕前HCMV IgC抗体阳性率高;时HCMV IgM抗体阳性孕前妇女应进行多指标检测以判断HCMV感染的状态,为减少出生缺陷、做好优生优育服务提供依据.%Objective: To investigate the infection state of human cytomegalovirus among women before pregnancy in Wenzhou region. Methods: Blood samples of 2869 free pre - pregnancy eugenic screening women in Lonwan District of Wenzhou City from Oct.2008 to Jun. 2010 were detected by enzyme- linked immunosorbent assay (ELISA) for HCMV IgG/IgM antibodies; HCMV DNA load was detected by real -time fluorescence quantitative polymerase chain reaction (FQ -PCR) in HCMV IgM antibody positive samples; IgG antibody avidity index (AI) was detected by urea degeneration combining ELISA in specimens which were positive of both HCMV IgG and IgM antibodies. Results: In 2 869 specimens of pre - pregnancy women, serum HCMV IgG antibodies positive rate was 97.77% (2 805/2 869), HCMV IgM antibodies positive rate was 0. 77% (22/2 869); IgG/IgM antibodies positive rate accounted for 0. 17% (5/2 869); in 22 HCMV IgM positive samples, blood HCMV DNA

  15. Aerobic bacteria, Chlamydia trachomatis, Pneumocystis carinii and Cytomegalovirus as agents of severe peneumonia in small infants Bactérias aeróbias, Chlamydia trachomatis, Pneumocystis carinii e Cytomegalovirus: agentes causadores de pneumonia grave em pequenos lactentes

    Directory of Open Access Journals (Sweden)

    Bernardo Ejzenberg

    1996-02-01

    Full Text Available The authors studied 58 infants hospitalized for pneumonia in a semi-intensive care unit. Age ranged from 1 complete to 6 incomplete months. The infants were sent from another hospital in 20 cases and from home in a further 38. Pulmonary involvement, which was alveolar in 46 cases and interstitial in 12, was bilateral in 31 children. The investigation was carried out prospectively on the etiological agents associated with respiratory infection to look for evidence of aerobic bacteria (blood cultures, Chlamydia trachomatis and Cytomegalovirus (serology, and Pneumocystis carinii (direct microscopy of tracheal aspirated material. The following infectious agents were diagnosed in 21 children (36.2%: Aerobic bacteria (8, Chlamydia trachomatis (5, Pneumocystis carinii (3, Cytomegalovirus (3, Cytomegalovirus and Chlamydia trachomatis (1, Aerobic bacteria and Cytomegalovirus (1. Seven cases of infection by Chlamydia trachomatis and/or Cytomegalovirus were diagnosed out of the 12 cases with pulmonary interstitial involvement.Os autores estudaram prospectivamente 58 lactentes internados por pneumonia em unidade semi-intensiva. A idade foi limitada entre 1 mês completo e 6 meses incompletos. A procedência das crianças foi de outro hospital em 20 casos e domiciliar em 38. O acometimento pulmonar era alveolar em 46 casos, intersticial em 12 e bilateral em 31 crianças. Foram pesquisados agentes etiológicos associados à infecção respiratória dos lactentes jovens: Bactérias aeróbias (Hemoculturas, Chlamydia trachomatis e Cytomegalovirus (sorologia, e Pneumocystis carinii (microscopia direta do aspirado traqueal. Foram diagnosticadas infecções em 21 crianças (36,2%: Bactérias aeróbias (8, Chlamydia trachomatis (5, Cytomegalovirus (3, Pneumocystis carinii (3, Cytomegalovirus e Chlamydia trachomatis (1, Bactéria aeróbia e Cytomegalovirus (1. Foram diagnosticadas 7 infecções por Chlamydia trachomatis e/ou Cytomegalovirus entre as 12 crianças com

  16. Reduction of phospholipase D activity during coxsackievirus infection.

    NARCIS (Netherlands)

    Duijsings, D.; Wessels, E.; Emst-de Vries, S.E. van; Melchers, W.J.G.; Willems, P.H.G.M.; Kuppeveld, F.J.M. van

    2007-01-01

    During enterovirus infection, host cell membranes are rigorously rearranged and modified. One ubiquitously expressed lipid-modifying enzyme that might contribute to these alterations is phospholipase D (PLD). Here, we investigated PLD activity in coxsackievirus-infected cells. We show that PLD activ

  17. Human cytomegalovirus and transplantation: drug development and regulatory issues.

    Science.gov (United States)

    McIntosh, Megan; Hauschild, Benjamin; Miller, Veronica

    2016-01-01

    Cytomegalovirus (CMV) infection is highly prevalent worldwide and can cause serious disease among immunocompromised individuals, including persons with HIV and transplant recipients on immunosuppressive therapies. It can also result in congenital cytomegalovirus when women are infected during pregnancy. Treatment and prevention of CMV in solid organ and haematopoietic stem cell transplant recipients is accomplished in one of three ways: (1) prophylactic therapy to prevent CMV viraemia; (2) pre-emptive therapy for those with low levels of replicating virus; and (3) treatment for established disease. Despite the high prevalence of CMV, there are few available approved drug therapies, and those that are available are hampered by toxicity and less-than-optimal efficacy. New therapies are being developed and tested; however, inconsistency in standardisation of virus levels and questions about potential endpoints in clinical trials present regulatory hurdles that must be addressed. This review covers the current state of CMV therapy, drugs currently under investigation, and clinical trial issues and questions that are in need of resolution. PMID:27482453

  18. Cytomegalovirus seropositivity is associated with herpes zoster.

    Science.gov (United States)

    Ogunjimi, Benson; Hens, Niel; Pebody, Richard; Jansens, Hilde; Seale, Holly; Quinlivan, Mark; Theeten, Heidi; Goossens, Herman; Breuer, Judy; Beutels, Philippe

    2015-01-01

    Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively recruited ambulatory adult HZ patients in the UK (N = 223) in order to compare the results with those from UK population samples (N = 1545) by means of a logistic regression (controlling for age and gender). Furthermore, we compared the UK population CMV seroprevalence with those from population samples from other countries (from Belgium (N1 = 1741, N2 = 576), USA (N = 5572) and Australia (N = 2080)). Furthermore, CMV IgG titers could be compared between UK HZ patients and Belgium N2 population samples because the same experimental set-up for analysis was used. We found UK ambulatory HZ patients to have a higher CMV seroprevalence than UK population samples (OR 1.56 [1.11 2.19]). CMV IgG seropositivity was a significant risk factor for HZ in the UK (OR 3.06 [1.32 7.04]. Furthermore, high CMV IgG titers (exceeding the upper threshold) were less abundant in CMV-seropositive Belgian N2 population samples than in CMV-seropositive UK HZ patients (OR 0.51 [0.31 0.82]. We found CMV-seroprevalence to increase faster with age in the UK than in other countries (P < 0.05). We conclude that CMV IgG seropositivity is associated with HZ. This finding could add to the growing list of risk factors for HZ. PMID:25905443

  19. Human cytomegaloviruses expressing yellow fluorescent fusion proteins--characterization and use in antiviral screening.

    Directory of Open Access Journals (Sweden)

    Sarah Straschewski

    Full Text Available Recombinant viruses labelled with fluorescent proteins are useful tools in molecular virology with multiple applications (e.g., studies on intracellular trafficking, protein localization, or gene activity. We generated by homologous recombination three recombinant cytomegaloviruses carrying the enhanced yellow fluorescent protein (EYFP fused with the viral proteins IE-2, ppUL32 (pp150, and ppUL83 (pp65. In growth kinetics, the three viruses behaved all like wild type, even at low multiplicity of infection (MOI. The expression of all three fusion proteins was detected, and their respective localizations were the same as for the unmodified proteins in wild-type virus-infected cells. We established the in vivo measurement of fluorescence intensity and used the recombinant viruses to measure inhibition of viral replication by neutralizing antibodies or antiviral substances. The use of these viruses in a pilot screen based on fluorescence intensity and high-content analysis identified cellular kinase inhibitors that block viral replication. In summary, these viruses with individually EYFP-tagged proteins will be useful to study antiviral substances and the dynamics of viral infection in cell culture.

  20. Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

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    Haidar A. Shamran

    2015-01-01

    Full Text Available Human Cytomegalovirus (HCMV is an endemic herpes virus that reemerges in cancer patients enhancing oncogenic potential. HCMV infection is associated with certain types of cancer morbidity such as glioblastomas. HCMV, like all other herpes viruses, has the ability to remain latent within the body of the host and can contribute in chronic inflammation. To determine the role of HCMV in glioma pathogenesis, paraffin-embedded blocks from glioma patients (n=50 and from benign meningioma patients (n=30 were obtained and evaluated by immunohistochemistry and polymerase chain reaction for the evidence of HCMV antigen expression and the presence of viral DNA. We detected HCMV antigen and DNA for IEI-72, pp65, and late antigen in 33/36, 28/36, and 26/36 in glioblastoma multiforme patients whereas 12/14, 10/14, and 9/14 in anaplastic astrocytoma patients, respectively. Furthermore, 84% of glioma patients were positive for immunoglobulin G (IgG compared to 72.5% among control samples (P=0.04. These data indicate the presence of the HCMV virus in a high percentage of glioma samples demonstrating distinct histopathological grades and support previous reports showing the presence of HCMV infection in glioma tissue. These studies demonstrate that detection of low-levels of latent viral infections may play an active role in glioma development and pathogenesis.

  1. PREVALENCE OF CYTOMEGALOVIRUS IN CHILDREN WHO RECEIVE BONE MARROW TRANSPLANTATION BY MEANS OF REAL-TIME POLYMERASE CHAIN REACTION

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    López-Montanero Edith Elizabeth

    2015-01-01

    Full Text Available Introduction: The citomegalovirus (CMV is an important virus worldwide. The early and mass-produced detection of the viral load for CMV helps to treat in an early way the infection and to avoid the disease in immunodeficient patients that in several cases could be lethal. Objective: To determine the prevalence of CMV in immunodeficient children who received bone marrow transplantation by means of real-time polymerase chain reaction. Methods: Retrospective, descriptive and cross-sectional study. The viral load was determined in plasma samples recollected since 2009 to 2012 in children who received bone marrow transplantation in the Hospital de la Sociedad de Lucha contra el Cáncer (SOLCA in Guayaquil, Ecuador. Results: 38 samples were analyzed. The average age was 7.2 years, and 57.9% (n=22 were men and 42.1% (n=16 women, with a male-female relationship 1:4. Of the analyzed samples, five patients presented positive results in the mentioned technique, who were the 80% of the female gender. And the population with the higher number of cases with positive results were Los Ríos, Guayas and Esmeraldas. The patients who were transplanted due to acute lymphoblastic leukemia and lymphoma with leukemization to acute lymphoblastic leukemia had positive results for active infection by CMV, 80% and 20%, respectively. Conclusion: The prevalence of CMV in children who received bone marrow transplantation by means of real-time polymerase chain reaction was of 13%, higher in the female gender. Rev.cienc.biomed. 2015;6(1:53-59 KEYWORDS Cytomegalovirus; Cytomegalovirus Infections; Transplant Recipients; Polymerase Chain Reaction.

  2. Activity of antiretroviral drugs in human infections by opportunistic agents

    OpenAIRE

    Izabel Galhardo Demarchi; Daniela Maira Cardozo; Sandra Mara Alessi Aristides; Ricardo Alberto Moliterno; Thaís Gomes Verzignassi Silveira; Rosilene Fressatti Cardoso; Dennis Armando Bertolini; Terezinha Inez Estivalet Svidzinski; Jorge Juarez Vieira Teixeira; Maria Valdrinez Campana Lonardoni

    2012-01-01

    Highly active antiretroviral therapy (HAART) is used in patients infected with HIV. This treatment has been shown to significantly decrease opportunist infections such as those caused by viruses, fungi and particularly, protozoa. The use of HAART in HIV-positive persons is associated with immune reconstitution as well as decreased prevalence of oral candidiasis and candidal carriage. Antiretroviral therapy benefits patients who are co-infected by the human immunodeficiency virus (HIV), human ...

  3. The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

    Directory of Open Access Journals (Sweden)

    Michael Nevels

    2009-11-01

    Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

  4. Down-regulation of human cytomegalovirus UL138, a novel latency-associated determinant, by hcmv-miR-UL36

    Indian Academy of Sciences (India)

    Yujing Huang; Ying Qi; Yanping Ma; Rong He; Yaohua Ji; Zhengrong Sun; Qiang Ruan

    2013-09-01

    MicroRNAs (miRNAs) are small RNAs, 19–23 nucleotides in length, which regulate a variety of cellular processes. Human cytomegalovirus (HCMV) encodes only one intronic miRNA: human cytomegalovirus microRNA UL36 (hcmv-miR-UL36). In this study, we found that over-expression of hcmv-miR-UL36 resulted in a more than threefold increase in HCMV DNA synthesis at 24 h post infection. Fifteen putative targets of hcmv-miR-UL36 were identified using hybrid PCR, one being the HCMV UL138 gene that has previously been identified as a novel latency-associated determinant of HCMV infection. Down-regulation of UL138 expression by hcmv-miR-UL36 was validated using luciferase reporter assays and Western blot analysis in HEK293 cells. In the presence of hcmv-miR-UL36, we observed a 74.6% decrease in luciferase activity and a 46.2% decrease in HCMV UL138 protein expression. Our results indicate that hcmv-miR-UL36 may be a viral miRNA contributing to HCMV replication.

  5. Human cytomegalovirus inhibits a DNA damage response by mislocalizing checkpoint proteins

    Science.gov (United States)

    Gaspar, Miguel; Shenk, Thomas

    2006-02-01

    The DNA damage checkpoint pathway responds to DNA damage and induces a cell cycle arrest to allow time for DNA repair. Several viruses are known to activate or modulate this cellular response. Here we show that the ataxia-telangiectasia mutated checkpoint pathway, which responds to double-strand breaks in DNA, is activated in response to human cytomegalovirus DNA replication. However, this activation does not propagate through the pathway; it is blocked at the level of the effector kinase, checkpoint kinase 2 (Chk2). Late after infection, several checkpoint proteins, including ataxia-telangiectasia mutated and Chk2, are mislocalized to a cytoplasmic virus assembly zone, where they are colocalized with virion structural proteins. This colocalization was confirmed by immunoprecipitation of virion proteins with an antibody that recognizes Chk2. Virus replication was resistant to ionizing radiation, which causes double-strand breaks in DNA. We propose that human CMV DNA replication activates the checkpoint response to DNA double-strand breaks, and the virus responds by altering the localization of checkpoint proteins to the cytoplasm and thereby inhibiting the signaling pathway. ionizing radiation | ataxia-telangiectasia mutated pathway

  6. Cytomegalovirus retinitis after central retinal vein occlusion in a patient on systemic immunosuppression: does venooclusive disease predispose to cytomegalovirus retinitis in patients already at risk?

    Directory of Open Access Journals (Sweden)

    Welling JD

    2012-04-01

    Full Text Available John D Welling, Ahmad B Tarabishy, John ChristoforidisDepartment of Ophthalmology, Havener Eye Institute, Ohio State University, Columbus, OH, USAAbstract: Cytomegalovirus (CMV retinitis remains the most common opportunistic ocular infection in immunocompromised patients. Patients with immunocompromising diseases, such as acquired immunodeficiency syndrome, inherited immunodeficiency states, malignancies, and those on systemic immunosuppressive therapy, are known to be at risk. Recently, it has been suggested that patients undergoing intravitreal injection of immunosuppressive agents may also be predisposed. One previous case report speculated that there may be an additional risk for CMV retinitis in acquired immunodeficiency syndrome patients with venoocclusive disease. This case study presents a case of CMV retinitis following central retinal vein occlusion in a patient on systemic immunosuppressants.Keywords: cytomegalovirus retinitis, central retinal vein occlusion, immunosuppression, solid organ transplant, venous stasis, risk factor

  7. Elimination of ie1 significantly attenuates murine cytomegalovirus virulence but does not alter replicative capacity in cell culture.

    NARCIS (Netherlands)

    P. Ghazal; A.E. Visser; M. Gustems; R. Garcia; E.M. Borst; K. Sullivan; M. Messerle; A. Angulo

    2005-01-01

    The major immediate-early (MIE) genes of cytomegaloviruses (CMV) are broadly thought to be decisive regulators of lytic replication and reactivation from latency. To directly assess the role of the MIE protein IE1 during the infection of murine CMV (MCMV), we constructed an MCMV with exon 4 of the i

  8. Ileitis econdary to cytomegalovirus in a Healthy patient: report of a case and review of the literature

    International Nuclear Information System (INIS)

    We report a case of primary cytomegalovirus (CMV) infection with intestinal and hepatic involvement in a young, previously healthy patient who presented none of the associated risk factors. The radiological findings are analyzed and the literature is reviewed. (Author) 11 refs

  9. Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway.

    Science.gov (United States)

    Gardner, Thomas J; Tortorella, Domenico

    2016-09-01

    The prototypic herpesvirus human cytomegalovirus (CMV) exhibits the extraordinary ability to establish latency and maintain a chronic infection throughout the life of its human host. This is even more remarkable considering the robust adaptive immune response elicited by infection and reactivation from latency. In addition to the ability of CMV to exist in a quiescent latent state, its persistence is enabled by a large repertoire of viral proteins that subvert immune defense mechanisms, such as NK cell activation and major histocompatibility complex antigen presentation, within the cell. However, dissemination outside the cell presents a unique existential challenge to the CMV virion, which is studded with antigenic glycoprotein complexes targeted by a potent neutralizing antibody response. The CMV virion envelope proteins, which are critical mediators of cell attachment and entry, possess various characteristics that can mitigate the humoral immune response and prevent viral clearance. Here we review the CMV glycoprotein complexes crucial for cell attachment and entry and propose inherent properties of these proteins involved in evading the CMV humoral immune response. These include viral glycoprotein polymorphism, epitope competition, Fc receptor-mediated endocytosis, glycan shielding, and cell-to-cell spread. The consequences of CMV virion glycoprotein-mediated immune evasion have a major impact on persistence of the virus in the population, and a comprehensive understanding of these evasion strategies will assist in designing effective CMV biologics and vaccines to limit CMV-associated disease. PMID:27307580

  10. Pseudorabies virus infection alters neuronal activity and connectivity in vitro.

    Directory of Open Access Journals (Sweden)

    Kelly M McCarthy

    2009-10-01

    Full Text Available Alpha-herpesviruses, including human herpes simplex virus 1 & 2, varicella zoster virus and the swine pseudorabies virus (PRV, infect the peripheral nervous system of their hosts. Symptoms of infection often include itching, numbness, or pain indicative of altered neurological function. To determine if there is an in vitro electrophysiological correlate to these characteristic in vivo symptoms, we infected cultured rat sympathetic neurons with well-characterized strains of PRV known to produce virulent or attenuated symptoms in animals. Whole-cell patch clamp recordings were made at various times after infection. By 8 hours of infection with virulent PRV, action potential (AP firing rates increased substantially and were accompanied by hyperpolarized resting membrane potentials and spikelet-like events. Coincident with the increase in AP firing rate, adjacent neurons exhibited coupled firing events, first with AP-spikelets and later with near identical resting membrane potentials and AP firing. Small fusion pores between adjacent cell bodies formed early after infection as demonstrated by transfer of the low molecular weight dye, Lucifer Yellow. Later, larger pores formed as demonstrated by transfer of high molecular weight Texas red-dextran conjugates between infected cells. Further evidence for viral-induced fusion pores was obtained by infecting neurons with a viral mutant defective for glycoprotein B, a component of the viral membrane fusion complex. These infected neurons were essentially identical to mock infected neurons: no increased AP firing, no spikelet-like events, and no electrical or dye transfer. Infection with PRV Bartha, an attenuated circuit-tracing strain delayed, but did not eliminate the increased neuronal activity and coupling events. We suggest that formation of fusion pores between infected neurons results in electrical coupling and elevated firing rates, and that these processes may contribute to the altered neural

  11. Cysteine protease activation and apoptosis in Murine norovirus infection

    Directory of Open Access Journals (Sweden)

    Ettayebi Khalil

    2009-09-01

    Full Text Available Abstract Background Noroviruses are the leading cause of viral gastroenteritis. Because a suitable in vitro culture system for the human virus has yet to be developed, many basic details of the infection process are unknown. Murine norovirus (MNV serves as a model system for the study of norovirus infection. Recently it was shown that infection of RAW 264.7 cells involved a novel apoptotic pathway involving survivin. Results Using a different set of approaches, the up-regulation of caspases, DNA condensation/fragmentation, and membrane blebbing, all of which are markers of apoptosis, were confirmed. Live cell imaging and activity-based protein profiling showed that activation of caspase-like proteases occurred within two hours of infection, followed by morphological changes to the cells. MNV infection in the presence of caspase inhibitors proceeded via a distinct pathway of rapid cellular necrosis and reduced viral production. Affinity purification of activity-based protein profiling targets and identification by peptide mass fingerprinting showed that the cysteine protease cathepsin B was activated early in infection, establishing this protein as an upstream activator of the intrinsic apoptotic pathway. Conclusion This work adds cathepsin B to the noncanonical programmed cell death induced by MNV, and provides data suggesting that the virus may induce apoptosis to expand the window of time for viral replication. This work also highlights the significant power of activity-based protein profiling in the study of viral pathogenesis.

  12. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis

    OpenAIRE

    Tan, Susanna K.; Burgener, Elizabeth B.; Waggoner, Jesse J.; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F.; Pinsky, Benjamin A.

    2016-01-01

    Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2...

  13. Role of human cytomegalovirus in the proliferation and invasion of extravillous cytotrophoblasts isolated from early placentae

    OpenAIRE

    Liu, Tao; Zheng, Xiaofei; Li, Qin; Chen, Juanjuan; Yin, Zongzhi; Xiao, Juan; Zhang, Dandan; Li, Wei; Qiao, Yuan; Chen, Suhua

    2015-01-01

    Aim: We investigated the role of human cytomegalovirus (HCMV) and its mechanism in extravillous cytotrophoblast (EVT) proliferation and invasion in vitro. Methods: Differential enzymatic digestion combined with gradient centrifugation, was used to isolate primary EVT from human chorionic villi collected from early placentae of healthy pregnant women. HCMV infection was determined by immunofluorescence staining of HCMVpp65 antigen expression. An MTT assay was used to examine the role of HCMV i...

  14. Case Report: Cytomegalovirus Primoinfection May Be Associated with Severe Outcome in Burns

    OpenAIRE

    Augris, C.; Benyamina, M.; Rozenberg, F; Gaucher, S.; Wassermann, D.; Vinsonneau, C.

    2007-01-01

    We report two cases of severe cytomegalovirus (CMV) primoinfection in seriously burned patients. The infection may have contributed to both patients' fatal outcome. This underlines the importance of research in viral aetiology, especially with regard to CMV, when immunodeficient patients - as burn patients are - develop unexplained fever. We propose a monitoring and a prevention strategy for CMV in the most severely burned patients. The prevention strategy involves the use of skin allografts ...

  15. Cytomegalovirus-associated superior mesenteric vein thrombosis treated with systemic and in-situ thrombolysis

    OpenAIRE

    Van Moerkercke, Wouter; Pauwelyn, Karen; Brugman, Eddy Maurice Paul; Verhamme, Marc

    2009-01-01

    A 56-year-old patient, first diagnosed with an acute cytomegalovirus infection, presented with progressive abdominal pain because of a superior mesenteric vein thrombosis for which he was treated with systemic thrombolysis and heparin in continuous infusion. As this therapy did not have the intended success after 5 days, an interventional radiological procedure was performed with local thrombolysis in the superior mesenteric artery resulting in recanalisation of the vein. Oral anticoagulation...

  16. Phenotype of villous stromal cells in placentas with cytomegalovirus, syphilis, and nonspecific villitis.

    OpenAIRE

    Greco, M A; Wieczorek, R.; Sachdev, R.; Kaplan, C.; Nuovo, G. J.; Demopoulos, R. I.

    1992-01-01

    Villous stromal cells (VSC) play an important role in fetomaternal placental immune function. We studied the phenotype of VSC in infection by cytomegalovirus (CMV) and syphilis as well as nonspecific villitis and compared the findings with gestational age-matched controls. Monoclonal antibodies directed against total leukocytes, T cells, B cells, macrophages, dendritic cells, granulocytes and HLA-DR as well as polyclonal antibodies against S-100, alpha-1 antichymotrypsin, and lysozyme were us...

  17. Cytomegalovirus m154 hinders CD48 cell-surface expression and promotes viral escape from host natural killer cell control.

    Directory of Open Access Journals (Sweden)

    Angela Zarama

    2014-03-01

    Full Text Available Receptors of the signalling lymphocyte-activation molecules (SLAM family are involved in the functional regulation of a variety of immune cells upon engagement through homotypic or heterotypic interactions amongst them. Here we show that murine cytomegalovirus (MCMV dampens the surface expression of several SLAM receptors during the course of the infection of macrophages. By screening a panel of MCMV deletion mutants, we identified m154 as an immunoevasin that effectively reduces the cell-surface expression of the SLAM family member CD48, a high-affinity ligand for natural killer (NK and cytotoxic T cell receptor CD244. m154 is a mucin-like protein, expressed with early kinetics, which can be found at the cell surface of the infected cell. During infection, m154 leads to proteolytic degradation of CD48. This viral protein interferes with the NK cell cytotoxicity triggered by MCMV-infected macrophages. In addition, we demonstrate that an MCMV mutant virus lacking m154 expression results in an attenuated phenotype in vivo, which can be substantially restored after NK cell depletion in mice. This is the first description of a viral gene capable of downregulating CD48. Our novel findings define m154 as an important player in MCMV innate immune regulation.

  18. Controlling Cytomegalovirus: Helping the Immune System Take the Lead

    Directory of Open Access Journals (Sweden)

    Patrick J. Hanley

    2014-05-01

    Full Text Available Cytomegalovirus, of the Herpesviridae family, has evolved alongside humans for thousands of years with an intricate balance of latency, immune evasion, and transmission. While upwards of 70% of humans have evidence of CMV infection, the majority of healthy people show little to no clinical symptoms of primary infection and CMV disease is rarely observed during persistent infection in immunocompetent hosts. Despite the fact that the majority of infected individuals are asymptomatic, immunologically, CMV hijacks the immune system by infecting and remaining latent in antigen-presenting cells that occasionally reactivate subclinically and present antigen to T cells, eventually causing the inflation of CMV-specific T cells until they can compromise up to 10% of the entire T cell repertoire. Because of this impact on the immune system, as well as its importance in fields such as stem cell and organ transplant, the relationship between CMV and the immune response has been studied in depth. Here we provide a review of many of these studies and insights into how CMV-specific T cells are currently being used therapeutically.

  19. Analysis of human cytomegalovirus using the polymerase chain reaction.

    Science.gov (United States)

    Mendelson, M

    2000-01-01

    As with numerous other branches of science, the study of human cytomegalovirus (HCMV) infection has been revolutionized by the polymerase chain reaction (PCR) method first devised by Mullis and Faloona (1). PCR allows the in vitro amplification of HCMV DNA sequences by the simultaneous primer extension of complementary DNA strands. Similarly, reverse transcription-PCR (RT-PCR) allows the study of targeted gene expression, by reverse transcription of RNA to complementary DNA (cDNA), followed by amplification of target DNA using predetermined primers. The PCR method is used in the clinical diagnosis of HCMV infection, particularly in the setting of transplantation medicine and in those patients infected with the human immunodeficiency virus (HIV). In addition, the advent of PCR and RT-PCR has transformed our understanding of the pathogenesis of HCMV infection, central to which is the definition of the sites of latency, the degree and type of gene expression within the latently infected cell, and the factors influencing both the maintenance of latency and reactivation of the virus during immunosuppression.

  20. Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators

    Science.gov (United States)

    Kim, Young-Eui; Lee, Myoung Kyu; Kwon, Ki Mun; Kim, Keun Il; Stamminger, Thomas; Ahn, Jin-Hyun

    2016-01-01

    Interferon-stimulated gene 15 (ISG15) encodes an ubiquitin-like protein that covalently conjugates protein. Protein modification by ISG15 (ISGylation) is known to inhibit the replication of many viruses. However, studies on the viral targets and viral strategies to regulate ISGylation-mediated antiviral responses are limited. In this study, we show that human cytomegalovirus (HCMV) replication is inhibited by ISGylation, but the virus has evolved multiple countermeasures. HCMV-induced ISG15 expression was mitigated by IE1, a viral inhibitor of interferon signaling, however, ISGylation was still strongly upregulated during virus infection. RNA interference of UBE1L (E1), UbcH8 (E2), Herc5 (E3), and UBP43 (ISG15 protease) revealed that ISGylation inhibits HCMV growth by downregulating viral gene expression and virion release in a manner that is more prominent at low multiplicity of infection. A viral regulator pUL26 was found to interact with ISG15, UBE1L, and Herc5, and be ISGylated. ISGylation of pUL26 regulated its stability and inhibited its activities to suppress NF-κB signaling and complement the growth of UL26-null mutant virus. Moreover, pUL26 reciprocally suppressed virus-induced ISGylation independent of its own ISGylation. Consistently, ISGylation was more pronounced in infections with the UL26-deleted mutant virus, whose growth was more sensitive to IFNβ treatment than that of the wild-type virus. Therefore, pUL26 is a viral ISG15 target that also counteracts ISGylation. Our results demonstrate that ISGylation inhibits HCMV growth at multiple steps and that HCMV has evolved countermeasures to suppress ISG15 transcription and protein ISGylation, highlighting the importance of the interplay between virus and ISGylation in productive viral infection. PMID:27564865

  1. Human cytomegalovirus-induced NKG2C(hi) CD57(hi) natural killer cells are effectors dependent on humoral antiviral immunity.

    Science.gov (United States)

    Wu, Zeguang; Sinzger, Christian; Frascaroli, Giada; Reichel, Johanna; Bayer, Carina; Wang, Li; Schirmbeck, Reinhold; Mertens, Thomas

    2013-07-01

    Recent studies indicate that expansion of NKG2C-positive natural killer (NK) cells is associated with human cytomegalovirus (HCMV); however, their activity in response to HCMV-infected cells remains unclear. We show that NKG2C(hi) CD57(hi) NK cells gated on CD3(neg) CD56(dim) cells can be phenotypically identified as HCMV-induced NK cells that can be activated by HCMV-infected cells. Using HCMV-infected autologous macrophages as targets, we were able to show that these NKG2C(hi) CD57(hi) NK cells are highly responsive to HCMV-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. We further demonstrate that NKG2C(hi) CD57(hi) NK cells are intrinsically responsive to signaling through CD16 cross-linking. Our findings show that the activity of pathogen-induced innate immune cells can be enhanced by adaptive humoral immunity. Understanding the activity of NKG2C(hi) CD57(hi) NK cells against HCMV-infected cells will be of relevance for the further development of adoptive immunotherapy.

  2. Immune parameters differentiating active from latent tuberculosis infection in humans.

    Science.gov (United States)

    Lee, Ji Yeon; Jung, Young Won; Jeong, Ina; Joh, Joon-Sung; Sim, Soo Yeon; Choi, Boram; Jee, Hyeon-Gun; Lim, Dong-Gyun

    2015-12-01

    Tuberculosis remains a highly prevalent infectious disease worldwide. Identification of the immune parameters that differentiate active disease from latent infection will facilitate the development of efficient control measures as well as new diagnostic modalities for tuberculosis. Here, we investigated the cytokine production profiles of monocytes and CD4(+) T lymphocytes upon encountering mycobacterial antigens. In addition, cytokines and lipid mediators with immune-modulating activities were examined in plasma samples ex vivo. Comparison of these parameters in active tuberculosis patients and healthy subjects with latent infection revealed that, active tuberculosis was associated with diminished Th1-type cytokine secretion from CD4(+) T cells and less augmented inflammatory cytokine secretion from monocytes induced by IFN-γ than that in latent tuberculosis infection. In addition, a higher plasma concentration of lipoxin A4 and lower ratio of prostaglandin E2 to lipoxin A4 were observed in active cases than in latent infections. These findings have implications for preparing new therapeutic strategies and for differential diagnosis of the two types of tuberculosis infection.

  3. Opportunistic infections and malignancies in 231 Danish AIDS patients

    DEFF Research Database (Denmark)

    Pedersen, C; Gerstoft, J; Tauris, P;

    1990-01-01

    diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion...

  4. Mutual Interference between Cytomegalovirus and Reconstitution of Protective Immunity after Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Reddehase, Matthias J

    2016-01-01

    Hematopoietic cell transplantation (HCT) is a therapy option for aggressive forms of hematopoietic malignancies that are resistant to standard antitumoral therapies. Hematoablative treatment preceding HCT, however, opens a "window of opportunity" for latent Cytomegalovirus (CMV) by releasing it from immune control with the consequence of reactivation of productive viral gene expression and recurrence of infectious virus. A "window of opportunity" for the virus represents a "window of risk" for the patient. In the interim between HCT and reconstitution of antiviral immunity, primarily mediated by CD8(+) T cells, initially low amounts of reactivated virus can expand exponentially, disseminate to essentially all organs, and cause multiple organ CMV disease, with interstitial pneumonia (CMV-IP) representing the most severe clinical manifestation. Here, I will review predictions originally made in the mouse model of experimental HCT and murine CMV infection, some of which have already paved the way to translational preclinical research and promising clinical trials of a preemptive cytoimmunotherapy of human CMV disease. Specifically, the mouse model has been pivotal in providing "proof of concept" for preventing CMV disease after HCT by adoptive transfer of preselected, virus epitope-specific effector and memory CD8(+) T cells bridging the critical interim. However, CMV is not a "passive antigen" but is a pathogen that actively interferes with the reconstitution of protective immunity by infecting bone marrow (BM) stromal cells that otherwise form niches for hematopoiesis by providing the structural microenvironment and by producing hematopoietically active cytokines, the hemopoietins. Depending on the precise conditions of HCT, reduced homing of transplanted hematopoietic stem- and progenitor cells to infected BM stroma and impaired colony growth and lineage differentiation can lead to "graft failure." In consequence, uncontrolled virus spread causes morbidity and

  5. Diagnóstico rápido de citomegalovirus (CMV en pacientes inmunocomprometidos mediante anticuerpos monoclonales que reconocen proteinas precoces virales Rapid diagnosis of cytomegalovirus infection in immunocompromised patients by using monoclonal antibodies against early viral antigens

    Directory of Open Access Journals (Sweden)

    Maritza Alvarez

    1989-06-01

    Full Text Available Se aplicó la técnica de detección de antigenos precoces fluorescentes (DAPF usando el anticuerpo monoclonal E-13 McAb, mediante el cual se lograron detectar 15 casos positivos a CMV de 75 muestras de orina o sangre ("buffy coat" tomadas de 52 pacientes inmunocomprometidos ingresados en el Instituto de Nefrología de ciudad Habana. Aplicando las técnicas clásicas de aislamiento en fibroblastos humanos diploides (MRC-5, se lograron aislar 12 cepas de CMV de casos previamente positivos por DAPF; lográndose además un aislamiento en una muestra reportada negativa por fluorescencia. Se observó una coincidencia de un 80% entre ambas técnicas. Se detectó la presencia de anticuerpos IgG contra CMV en todos los casos estudiados, utilizando para ello la técnica ELISA.A technique was applied to detect early fluorescent antigens (DEFA of cytomegalovirus (CMV using the E13 monoclonal antibodies in 52 immunocompromised patients hospitalized in the Nephrology Institute of Havana. Of the 75 urine or blood (buffy coat samples taken, 15 were found positive to CMV. Using classical diploide human fibroblast isolation technique, 12 CMV strains were isloation of previously detected positive samples by DEFA. In addition, CMV was isolated from one sample reported to be negative by DEFA. A coincidence of 80% was found between both techniques. With the ELISA test, all the sample studied have IgG antibodies to CMV.

  6. Fetal central nervous system anomalies induced by congenital cytomegalovirus infection%先天性CMV感染致中枢神经系统畸形发育机制

    Institute of Scientific and Technical Information of China (English)

    傅鹰; 陈利玉; 罗敏华

    2006-01-01

    胎儿中枢神经系统(central nervous system,CNS)是人类巨细胞病毒(human cytomegalovirus,HCMV)先天性感染的主要靶器官.胚胎期CMV感染常常导致严重CNS畸形的发生,其前提条件是CNS中的神经前体(干)细胞、神经元及神经胶质细胞对CMV普遍易感.发育期CNS感染CMV具有以下特点:(1)神经系统细胞对CMV的容纳性在CNS的不同发育阶段有所不同;(2)受累的细胞数随着发育的进展而增多;(3)CNS不同部位的细胞对CMV的敏感性存在明显的差异;(4)感染发生时细胞所处细胞周期的时相也与感染严重程度密切相关.CMV感染能诱导宿主细胞特异性的染色体折断,影响Homeobox基因(胚胎发育的主控基因)的表达,进而阻断细胞周期(G1期滞留)、诱导细胞凋亡,导致CNS细胞数量减少与迁徙异常,最终导致CNS发育畸形.

  7. Multiple host kinases contribute to Akt activation during Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Bernhard Roppenser

    Full Text Available SopB is a type 3 secreted effector with phosphatase activity that Salmonella employs to manipulate host cellular processes, allowing the bacteria to establish their intracellular niche. One important function of SopB is activation of the pro-survival kinase Akt/protein kinase B in the infected host cell. Here, we examine the mechanism of Akt activation by SopB during Salmonella infection. We show that SopB-mediated Akt activation is only partially sensitive to PI3-kinase inhibitors LY294002 and wortmannin in HeLa cells, suggesting that Class I PI3-kinases play only a minor role in this process. However, depletion of PI(3,4 P2/PI(3-5 P3 by expression of the phosphoinositide 3-phosphatase PTEN inhibits Akt activation during Salmonella invasion. Therefore, production of PI(3,4 P2/PI(3-5 P3 appears to be a necessary event for Akt activation by SopB and suggests that non-canonical kinases mediate production of these phosphoinositides during Salmonella infection. We report that Class II PI3-kinase beta isoform, IPMK and other kinases identified from a kinase screen all contribute to Akt activation during Salmonella infection. In addition, the kinases required for SopB-mediated activation of Akt vary depending on the type of infected host cell. Together, our data suggest that Salmonella has evolved to use a single effector, SopB, to manipulate a remarkably large repertoire of host kinases to activate Akt for the purpose of optimizing bacterial replication in its host.

  8. Human Cytomegalovirus UL44 Concentrates at the Periphery of Replication Compartments, the Site of Viral DNA Synthesis

    OpenAIRE

    Strang, Blair L.; Boulant, Steeve; Chang, Lynne; Knipe, David M.; Kirchhausen, Tomas; Coen, Donald M

    2012-01-01

    The formation of replication compartments, the subnuclear structures in which the viral DNA genome is replicated, is a hallmark of herpesvirus infections. The localization of proteins and viral DNA within human cytomegalovirus replication compartments is not well characterized. Immunofluorescence analysis demonstrated the accumulation of the viral DNA polymerase subunit UL44 at the periphery of replication compartments and the presence of different populations of UL44 in infected cells. In co...

  9. Latex agglutination and enzyme-linked immunosorbent assays for cytomegalovirus serologic screening of transplant donors and recipients.

    OpenAIRE

    Chou, S W; Scott, K M

    1988-01-01

    The effectiveness of three serologic assays (two enzyme-linked immunosorbent assays [ELISAs] and latex agglutination) for cytomegalovirus (CMV) serologic matching of donors and recipients was assessed over a 2-year period in a major organ transplant program. Sera with equivocal test results were investigated by repeat testing of serum samples and additional specimens from the individuals involved and monitoring of CMV infection in recipients. An in-house ELISA identified all CMV-infective don...

  10. Synthetic DNA approach to cytomegalovirus vaccine/immune therapy.

    Science.gov (United States)

    Wu, Stephan J; Villarreal, Daniel O; Shedlock, Devon J; Weiner, David B

    2015-01-01

    There is no licensed vaccine or cure for human cytomegalovirus (CMV), a ubiquitous β-herpes virus that infects 60-95 % of adults worldwide. Infection is a major cause of congenital abnormalities in newborns, contributes to development of childhood cerebral palsy and medulloblastoma, can result in severe disease in immunocompromised patients, and is a major impediment during successful organ transplantation. While CMV has been increasingly associated with numerous inflammatory diseases and cancers, only recently has it been correlated with increased risk of heart disease in adults, the number-one killer in the USA. These data, among others, suggest that subclinical CMV infection, or microinfection, in healthy individuals may play more of a causative role than an epiphenomenon in development of CMV-associated pathologies. Due to the myriad of diseases and complications associated with CMV, an efficacious vaccine would be highly valuable in reducing human morbidity and mortality as well as saving billions of dollars in annual health-care costs and disability adjusted life years (DALY) in the developing world. Therefore, the development of a safe efficacious CMV vaccine or immune therapy is paramount to the public health. This review aims to provide a brief overview on aspects of CMV infection and disease and focuses on current vaccine strategies. The use of new synthetic DNA vaccines might offer one such approach to this difficult problem.

  11. Coincident helminth infection modulates systemic inflammation and immune activation in active pulmonary tuberculosis.

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    Parakkal Jovvian George

    Full Text Available Helminth infections are known to modulate innate and adaptive immune responses in active and latent tuberculosis (TB. However, the role of helminth infections in modulating responses associated with inflammation and immune activation (reflecting disease activity and/or severity in TB is not known.We measured markers of inflammation and immune activation in active pulmonary TB individuals (ATB with co-incidental Strongyloides stercoralis (Ss infection. These included systemic levels of acute phase proteins, matrix metalloproteinases and their endogenous inhibitors and immune activation markers. As a control, we measured the systemic levels of the same molecules in TB-uninfected individuals (NTB with or without Ss infection.Our data confirm that ATB is associated with elevated levels of the various measured molecules when compared to those seen in NTB. Our data also reveal that co-incident Ss infection in ATB individuals is associated with significantly decreased circulating levels of acute phase proteins, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases as well as the systemic immune activation markers, sCD14 and sCD163. These changes are specific to ATB since they are absent in NTB individuals with Ss infection.Our data therefore reveal a profound effect of Ss infection on the markers associated with TB disease activity and severity and indicate that co-incidental helminth infections might dampen the severity of TB disease.

  12. Cytomegalovirus ileocolitis in a rheumatoid arthritis patient: case report and literature review

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    M. S. Dag

    2015-06-01

    Full Text Available Rheumatoid arthritis (RA is an autoimmune, systemic, chronic, inflammatory disease generally treated with various immunosuppressive drugs. Cytomegalovirus (CMV is an opportunistic, viral infection that is commonly seen in immunosuppressed patients. A sixty-four-year old female diagnosed with RA and treated with immunosuppressive agents was admitted to our rheumatology outpatient service with complaints of diarrhea and abdominal pain, which had lasted longer than four weeks. The patient’s colonoscopy revealed inflamed and ulcerated areas in the colon and in the terminal ileum. A biopsy showed intra-nuclear inclusion particles consistent with CMV. We started an oral valganciclovir therapy in this serum-CMV-polymerase chain reactionpositive patient. The concomitant use of immunosuppressive agents and anti-viral drugs eased the patient’s complaints, and the endoscopic picture improved. Consequently, cytomegalovirus ileocolitis in immunosuppressed patients admitted with severe diarrhea must be considered in the differential diagnosis.

  13. Toxoplasma gondii actively inhibits neuronal function in chronically infected mice.

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    Fahad Haroon

    Full Text Available Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii-infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca(2+ imaging studies revealed that tachyzoites actively manipulated Ca(2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca(2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca(2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host.

  14. Activation of an NLRP3 inflammasome restricts Mycobacterium kansasii infection.

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    Chang-Chieh Chen

    Full Text Available Mycobacterium kansasii has emerged as an important nontuberculous mycobacterium pathogen, whose incidence and prevalence have been increasing in the last decade. M. kansasii can cause pulmonary tuberculosis clinically and radiographically indistinguishable from that caused by Mycobacterium tuberculosis infection. Unlike the widely-studied M. tuberculosis, little is known about the innate immune response against M. kansasii infection. Although inflammasome activation plays an important role in host defense against bacterial infection, its role against atypical mycobacteria remains poorly understood. In this report, the role of inflammasome activity in THP-1 macrophages against M. kansasii infection was studied. Results indicated that viable, but not heat-killed, M. kansasii induced caspase-1-dependent IL-1β secretion in macrophages. The underlying mechanism was found to be through activation of an inflammasome containing the NLR (Nod-like receptor family member NLRP3 and the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD. Further, potassium efflux, lysosomal acidification, ROS production and cathepsin B release played a role in M. kansasii-induced inflammasome activation. Finally, the secreted IL-1β derived from caspase-1 activation was shown to restrict intracellular M. kansasii. These findings demonstrate a biological role for the NLRP3 inflammasome in host defense against M. kansasii.

  15. Disseminated rhodococcus equi infection in HIV infection despite highly active antiretroviral therapy

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    Ferretti Francesca

    2011-12-01

    Full Text Available Abstract Background Rhodococcus equi (R.equi is an acid fast, GRAM + coccobacillus, which is widespread in the soil and causes pulmonary and extrapulmonary infections in immunocompromised people. In the context of HIV infection, R.equi infection (rhodococcosis is regarded as an opportunistic disease, and its outcome is influenced by highly active antiretroviral therapy (HAART. Case presentation We report two cases of HIV-related rhodococcosis that disseminated despite suppressive HAART and anti-rhodococcal treatment; in both cases there was no immunological recovery, with CD4+ cells count below 200/μL. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years. Conclusions Our report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection.

  16. Cytomegalovirus retinitis in acquired immunodeficiency syndrome patients: A problem worth giving attention to

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    Priti Kapadia Gupta

    2014-01-01

    Full Text Available Background: Cytomegalovirus (CMV retinitis remains the most common ocular opportunistic infection in patients with acquired immunodeficiency syndrome even in the era of highly active antiretroviral therapy (HAART. Increased survival of patients on HAART has increased incidence of blindness, which will further increase in the future. The objective of this study was to determine the incidence of CMV retinitis and the effect of HAART on the natural history of CMV retinitis in patients referred from ART center. Materials and Methods: Patients with baseline/current CD4 counts <150 cells/µl were evaluated for CMV retinitis. Complete ophthalmological evaluation was carried out and records of CD4 counts, HAART regime, presence of any form of CMV retinitis and response to HAART were noted. Results: Out of 800 patients registered with CD4 <150 cells/µl in ART center, 100 patients reached us. Among these, CMV retinitis was observed in 15% patients, with median CD4 count at the time of examination being 56 cells/µl (range: 24-306 cells/µl. 66.67% patients were HAART non-responders and 63.6% eyes were economically blind. Conclusion: CMV retinitis occurs even in patients with higher CD4 counts. Timely diagnosis and intervention of this treatable condition can reduce the number of blinding years in these young patients who otherwise live longer as a result of HAART.

  17. Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape

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    Landolfo, Santo; De Andrea, Marco; Dell’Oste, Valentina; Gugliesi, Francesca

    2016-01-01

    Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed “restriction factors” (RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus (HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell’s intrinsic immune defenses. RFs include nuclear proteins IFN-γ inducible protein 16 (IFI16) (a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and hDaxx; the latter three being the keys elements of nuclear domain 10 (ND10). IFI16 inhibits the synthesis of virus DNA by down-regulating UL54 transcription - a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65 (pUL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents. PMID:27563536

  18. Molecular and Biological Characterization of a New Isolate of Guinea Pig Cytomegalovirus

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    Mark R. Schleiss

    2014-01-01

    Full Text Available Development of a vaccine against congenital infection with human cytomegalovirus is complicated by the issue of re-infection, with subsequent vertical transmission, in women with pre-conception immunity to the virus. The study of experimental therapeutic prevention of re-infection would ideally be undertaken in a small animal model, such as the guinea pig cytomegalovirus (GPCMV model, prior to human clinical trials. However, the ability to model re-infection in the GPCMV model has been limited by availability of only one strain of virus, the 22122 strain, isolated in 1957. In this report, we describe the isolation of a new GPCMV strain, the CIDMTR strain. This strain demonstrated morphological characteristics of a typical Herpesvirinae by electron microscopy. Illumina and PacBio sequencing demonstrated a genome of 232,778 nt. Novel open reading frames ORFs not found in reference strain 22122 included an additional MHC Class I homolog near the right genome terminus. The CIDMTR strain was capable of dissemination in immune compromised guinea pigs, and was found to be capable of congenital transmission in GPCMV-immune dams previously infected with salivary gland‑adapted strain 22122 virus. The availability of a new GPCMV strain should facilitate study of re-infection in this small animal model.

  19. Inner ear infections as cause of perinatal deafness

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    Vikas Gupta

    2012-01-01

    Full Text Available Objective: To assess the role of infective agents as cause of sensorineural hearing loss (SNHL in children. Setting: Tertiary care center actively involved in management of hearing impairment through cochlear implant program and other rehabilitation program. Materials and Methods: Retrospective chart review of 213 patients who underwent cochlear implantation at our center from 2007 to 2011 was carried out. Out of these, 185 were children. We have done the data analysis with regard to etiology of hearing loss in these 185 children. An etiology for SNHL could be established in 100 out of these 185 cases. Out of these 100 cases, we have further segregated cases where an infectious etiology was implicated. Results: Out of 185 prelingual cochlear implantees, etiology could be determined in 100 cases. Etiology was of infective origin in 26 of these 100 cases. Infective agents implicated in congenital acquired hearing loss were Toxoplasma, Rubella, Cytomegalovirus, and Herpes (TORCH infections ( n = 9 including Rubella ( n = 7 and Cytomegalovirus (CMV ( n = 2. Meningitis ( n = 11 and other infections ( n = 6 were responsible for secondary acquired hearing loss. Conclusions: Results showed that among the identified causes, infective agents were responsible in one-fourth cases of profound SNHL. Building awareness about such existence and their major role in causing SNHL among the otolaryngologists, pediatricians, obstetricians, physicians, audiologists and public is considered essential so that such preventable and controllable maladies are reduced by combined efforts from all these stakeholders.

  20. Activation of innate immunity during systemic Candida infections

    NARCIS (Netherlands)

    Ifrim, D.C.

    2015-01-01

    Despite the increased knowledge on the mechanisms of Candida recognition and the networks of innate and adaptive host defense activated during infection, much remains to be learned regarding the distinctive modulatory effects of Candida spp on host immune responses. We showed that the chronic exposu

  1. Activation of Natural Killer cells during microbial infections

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    Amir eHorowitz

    2012-01-01

    Full Text Available Natural killer (NK cells are large granular lymphocytes that express a diverse array of germline encoded inhibitory and activating receptors for MHC Class I and Class I-like molecules, classical co-stimulatory ligands and cytokines. The ability of NK cells to be very rapidly activated by inflammatory cytokines, to secrete effector cytokines and to kill infected or stressed host cells, suggests that they may be among the very early responders during infection. Recent studies have also identified a small number of pathogen-derived ligands that can bind to NK cell surface receptors and directly induce their activation. Here we review recent studies that have begun to elucidate the various pathways by which viral, bacterial and parasite pathogens activate NK cells. We also consider two emerging themes of NK cell-pathogen interactions, namely their contribution to adaptive immune responses and their potential to take on regulatory and immunomodulatory functions.

  2. Efficacy and Mechanism of Action of Low Dose Emetine against Human Cytomegalovirus.

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    Rupkatha Mukhopadhyay

    2016-06-01

    Full Text Available Infection with human cytomegalovirus (HCMV is a threat for pregnant women and immunocompromised hosts. Although limited drugs are available, development of new agents against HCMV is desired. Through screening of the LOPAC library, we identified emetine as HCMV inhibitor. Additional studies confirmed its anti-HCMV activities in human foreskin fibroblasts: EC50-40±1.72 nM, CC50-8±0.56 μM, and selectivity index of 200. HCMV inhibition occurred after virus entry, but before DNA replication, and resulted in decreased expression of viral proteins. Synergistic virus inhibition was achieved when emetine was combined with ganciclovir. In a mouse CMV (MCMV model, emetine was well-tolerated, displayed long half-life, preferential distribution to tissues over plasma, and effectively suppressed MCMV. Since the in vitro anti-HCMV activity of emetine decreased significantly in low-density cells, a mechanism involving cell cycle regulation was suspected. HCMV inhibition by emetine depended on ribosomal processing S14 (RPS14 binding to MDM2, leading to disruption of HCMV-induced MDM2-p53 and MDM2-IE2 interactions. Irrespective of cell density, emetine induced RPS14 translocation into the nucleus during infection. In infected high-density cells, MDM2 was available for interaction with RPS14, resulting in disruption of MDM2-p53 interaction. However, in low-density cells the pre-existing interaction of MDM2-p53 could not be disrupted, and RPS14 could not interact with MDM2. In high-density cells the interaction of MDM2-RPS14 resulted in ubiquitination and degradation of RPS14, which was not observed in low-density cells. In infected-only or in non-infected emetine-treated cells, RPS14 failed to translocate into the nucleus, hence could not interact with MDM2, and was not ubiquitinated. HCMV replicated similarly in RPS14 knockdown or control cells, but emetine did not inhibit virus replication in the former cell line. The interaction of MDM2-p53 was maintained

  3. Efficacy and Mechanism of Action of Low Dose Emetine against Human Cytomegalovirus.

    Science.gov (United States)

    Mukhopadhyay, Rupkatha; Roy, Sujayita; Venkatadri, Rajkumar; Su, Yu-Pin; Ye, Wenjuan; Barnaeva, Elena; Mathews Griner, Lesley; Southall, Noel; Hu, Xin; Wang, Amy Q; Xu, Xin; Dulcey, Andrés E; Marugan, Juan J; Ferrer, Marc; Arav-Boger, Ravit

    2016-06-01

    Infection with human cytomegalovirus (HCMV) is a threat for pregnant women and immunocompromised hosts. Although limited drugs are available, development of new agents against HCMV is desired. Through screening of the LOPAC library, we identified emetine as HCMV inhibitor. Additional studies confirmed its anti-HCMV activities in human foreskin fibroblasts: EC50-40±1.72 nM, CC50-8±0.56 μM, and selectivity index of 200. HCMV inhibition occurred after virus entry, but before DNA replication, and resulted in decreased expression of viral proteins. Synergistic virus inhibition was achieved when emetine was combined with ganciclovir. In a mouse CMV (MCMV) model, emetine was well-tolerated, displayed long half-life, preferential distribution to tissues over plasma, and effectively suppressed MCMV. Since the in vitro anti-HCMV activity of emetine decreased significantly in low-density cells, a mechanism involving cell cycle regulation was suspected. HCMV inhibition by emetine depended on ribosomal processing S14 (RPS14) binding to MDM2, leading to disruption of HCMV-induced MDM2-p53 and MDM2-IE2 interactions. Irrespective of cell density, emetine induced RPS14 translocation into the nucleus during infection. In infected high-density cells, MDM2 was available for interaction with RPS14, resulting in disruption of MDM2-p53 interaction. However, in low-density cells the pre-existing interaction of MDM2-p53 could not be disrupted, and RPS14 could not interact with MDM2. In high-density cells the interaction of MDM2-RPS14 resulted in ubiquitination and degradation of RPS14, which was not observed in low-density cells. In infected-only or in non-infected emetine-treated cells, RPS14 failed to translocate into the nucleus, hence could not interact with MDM2, and was not ubiquitinated. HCMV replicated similarly in RPS14 knockdown or control cells, but emetine did not inhibit virus replication in the former cell line. The interaction of MDM2-p53 was maintained in infected RPS14

  4. Childhood environments and cytomegalovirus serostatus and reactivation in adults.

    Science.gov (United States)

    Janicki-Deverts, Denise; Cohen, Sheldon; Doyle, William J; Marsland, Anna L; Bosch, Jos

    2014-08-01

    Childhood adversity, defined in terms of material hardship or physical or emotional maltreatment has been associated with risk for infection with cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation in children and adults. The present study examined whether different dimensions of childhood experience-those pertaining to socioeconomic status (SES), physical environment, or family relationships-relate differentially to CMV serostatus and reactivation during adulthood. Participants were 140 healthy adults, aged 18-55years (41% female; 64% white). Childhood environments were assessed retrospectively and included family SES (parental housing tenure); childhood neighborhood environment (urban residence; physical conditions; safety; and social atmosphere); residential exposures (parental smoking and physical condition of home); and family relationships (parental divorce; warmth; harmony; dysfunction; parental bonding). Approximately 39% (n=53) of participants were CMV+. In individual analyses controlling for age, sex, race, body mass, current adult SES and smoking status, fewer years of parental home ownership, having a parent who smoked, and living in a poorly maintained or unsafe neighborhood each were associated with greater odds of infection with CMV. By comparison, in individual analyses limited to CMV+ participants, less family warmth, less harmony, greater dysfunction, and suboptimal parental bonding each were related to higher antibody levels, independent of the aforementioned covariates. Findings were not attributable to current adult perceptions of psychological stress or relative levels of emotional stability. These results suggest that different types of childhood adversity may be associated with differential effects on CMV infection and latency.

  5. Childhood environments and cytomegalovirus serostatus and reactivation in adults.

    Science.gov (United States)

    Janicki-Deverts, Denise; Cohen, Sheldon; Doyle, William J; Marsland, Anna L; Bosch, Jos

    2014-08-01

    Childhood adversity, defined in terms of material hardship or physical or emotional maltreatment has been associated with risk for infection with cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation in children and adults. The present study examined whether different dimensions of childhood experience-those pertaining to socioeconomic status (SES), physical environment, or family relationships-relate differentially to CMV serostatus and reactivation during adulthood. Participants were 140 healthy adults, aged 18-55years (41% female; 64% white). Childhood environments were assessed retrospectively and included family SES (parental housing tenure); childhood neighborhood environment (urban residence; physical conditions; safety; and social atmosphere); residential exposures (parental smoking and physical condition of home); and family relationships (parental divorce; warmth; harmony; dysfunction; parental bonding). Approximately 39% (n=53) of participants were CMV+. In individual analyses controlling for age, sex, race, body mass, current adult SES and smoking status, fewer years of parental home ownership, having a parent who smoked, and living in a poorly maintained or unsafe neighborhood each were associated with greater odds of infection with CMV. By comparison, in individual analyses limited to CMV+ participants, less family warmth, less harmony, greater dysfunction, and suboptimal parental bonding each were related to higher antibody levels, independent of the aforementioned covariates. Findings were not attributable to current adult perceptions of psychological stress or relative levels of emotional stability. These results suggest that different types of childhood adversity may be associated with differential effects on CMV infection and latency. PMID:24675032

  6. Analysis of colorectal cancers for human cytomegalovirus presence

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    Menestrina Fabio

    2009-04-01

    Full Text Available Abstract Background A possible association between human cytomegalovirus (HCMV infection and colorectal cancer progression has been inferred by the identification in tumour tissues of HCMV antigens and specific viral DNA or RNA sequences. To further investigate the relationship between HCMV and colorectal cancers we developed qualitative and quantitative PCR assay to detect HCMV DNA in 56 formalin-fixed paraffin-embedded (FFPE tissue samples from patients belonging to 4 different histological phenotypes: adenoma; poorly, moderately and well differentiated adenocarcinomas. Results Of the 56 FFPE tested tissue samples, 6 (11% were positive for HCMV nested PCR amplification, and more precisely 1 (5% of 20 cases of adenoma and 5 (21% of 24 cases of moderately differentiated adenocarcinoma. No PCR positivity was obtained in samples from well and poorly differentiated adenocarcinomas. Conclusion Our observations suggest that there is no evidence of a direct association between HCMV and colorectal cancer. Moreover, the results obtained are not supportive of a causal role of HCMV in the processes of carcinogenesis and/or progression of colorectal cancer. However, the fact that the virus may present a "hit and run" like-mechanism and HCMV can thus only be detectable at a particular stage of a processing adenocarcinoma, suggests that a significant number of colorectal cancers might have been the subject of HCMV infection that could contribute to trigger the oncogenic differentiation. Our analysis does not exclude the possibility of HCMV infection subsequent viral clearance.

  7. The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis

    DEFF Research Database (Denmark)

    Waldhoer, Maria; Casarosa, Paola; Rosenkilde, Mette M;

    2003-01-01

    US28 is one of four 7 transmembrane (7TM) chemokine receptors encoded by human cytomegalovirus and has been shown to both signal and endocytose in a ligand-independent, constitutively active manner. Here we show that the constitutive activity and constitutive endocytosis properties of US28 are se...

  8. 人巨细胞病毒pp65 IgG亲和指数在人巨细胞病毒原发感染小鼠模型中的标志作用%The effect of the human cytomegalovirus pp65 IgG-avidity index for the human cytomegalovirus primary infection in mice model

    Institute of Scientific and Technical Information of China (English)

    刘倩; 王明丽

    2008-01-01

    Objective To investigate the significance of human cyomeg Movirus(HCMV)pp65 IgG antibody avidity index(AI)for the clinical diagnosis of HCMV primary infection through the experimental model of HCMV primaly infection in BALB/c mice.Methods 6~8 weeks,female,specific-pathogen-free BALB/c mice were divided into 5 groups.6 mice in each group. And he mice were injected with 2×106 PFU/m1,2×105 PFU/mi,2×104 PFU/ml,2×103 PFU/ml and 2×102 PFU/ml of HCMV intraperitoneally respectively. Another 6 mice were injected intraperitoneally with the maximum dose of HCMV kept at 56℃ for 30 min as inactivated virus group.And HF negative control group was established at same time. All the mice ere sacrificed to obtain brain and lung tissues for the following experiments after 1 montll.(1)Tissue samples obtained from mice were inoculated in human embryo fibroblasts(HF)monolayers after routine treatment for virus isolation.HCMV specific eytopathie effect(CPE) was observed bv inverted phase-contrast microscopy.HCMV UL83 DNA in the ultures as tested by PCR and pp65 antigen was detected by indirect immunofluorescence.(2)Extracted mRNA from tissue samples and HCMV pp67 mRNA were analyzed by reverse transcriptase PCR(RT-PcR).(3)Immunoglobulin M(IgM)antibody and immunoglobulin G(1gG)antibody avidity Was investigated for their usefulness in distinguishing primary genital HCMV infections rom nonprimary infections with ELISA kit using truncated pp65 protein.ResultsHCMV can be isolated in the tissues from the mice injected with 2×106 PFU/ml and 2×105 PFU/m1.RT- PCR and ELISA showed positive results in the same groups.The infective rates were 100%.The analysis of the low doses groups,inactivated group and HF negative ontrol group all showed negative results.Conclusions BALB/c mice can be infected with HCMV and appeared as primary infection after1 month.Determination of HCMV pp65 IgM and HCMV p065 IgG-AI by ELISA incorporated with virus isolation and RT-PCR are helpful for distinguishing

  9. Innate immune recognition and activation during HIV infection

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    Larsen Carsten S

    2010-06-01

    Full Text Available Abstract The pathogenesis of HIV infection, and in particular the development of immunodeficiency, remains incompletely understood. Whichever intricate molecular mechanisms are at play between HIV and the host, it is evident that the organism is incapable of restricting and eradicating the invading pathogen. Both innate and adaptive immune responses are raised, but they appear to be insufficient or too late to eliminate the virus. Moreover, the picture is complicated by the fact that the very same cells and responses aimed at eliminating the virus seem to play deleterious roles by driving ongoing immune activation and progressive immunodeficiency. Whereas much knowledge exists on the role of adaptive immunity during HIV infection, it has only recently been appreciated that the innate immune response also plays an important part in HIV pathogenesis. In this review, we present current knowledge on innate immune recognition and activation during HIV infection based on studies in cell culture, non-human primates, and HIV-infected individuals, and discuss the implications for the understanding of HIV immunopathogenesis.

  10. Urinary tract infections and pyelonephritis

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970374 The relationship between chronic pyelitis andcytomegalovirus infection: a primary study. LI Na(李娜), et al. 81021st Milit Hosp, Changchun,130021. Chin J Med Lab Sci 1997; 20(1): 26-27. Objective: To research the relationship betweenchronic pyelitis and cytomegalovirus (CMV) infection.

  11. Cytomegalovirus upregulates expression of CCR5 in central memory cord blood mononuclear cells, which may facilitate in utero HIV type 1 transmission.

    Science.gov (United States)

    Johnson, Erica L; Howard, Chanie L; Thurman, Joy; Pontiff, Kyle; Johnson, Elan S; Chakraborty, Rana

    2015-01-15

    Administration of combination antiretroviral therapy to human immunodeficiency virus type 1 (HIV-1)-infected pregnant women significantly reduces vertical transmission. In contrast, maternal co-opportunistic infection with primary or reactivated cytomegalovirus (CMV) or other pathogens may facilitate in utero transmission of HIV-1 by activation of cord blood mononuclear cells (CBMCs). Here we examine the targets and mechanisms that affect fetal susceptibility to HIV-1 in utero. Using flow cytometry, we demonstrate that the fraction of CD4(+)CD45RO(+) and CD4(+)CCR5(+) CBMCs is minimal, which may account for the low level of in utero HIV-1 transmission. Unstimulated CD4(+) CBMCs that lack CCR5/CD45RO showed reduced levels of HIV-1 infection. However, upon in vitro stimulation with CMV, CBMCs undergo increased proliferation to upregulate the fraction of T central memory cells and expression of CCR5, which enhances susceptibility to HIV-1 infection in vitro. These data suggest that activation induced by CMV in vivo may alter CCR5 expression in CD4(+) T central memory cells to promote in utero transmission of HIV-1.

  12. Detection of cytomegalovirus DNA in serum correlates with clinical cytomegalovirus retinitis in AIDS

    DEFF Research Database (Denmark)

    Hansen, K K; Ricksten, A; Hofmann, B;

    1994-01-01

    The high sensitivity of nested polymerase chain reaction (PCR) offers the possibility of rapid detection of cytomegalovirus (CMV) DNA in serum. Five consecutive serum samples were examined from 52 human immunodeficiency virus (HIV)-seropositive patients (19 of whom had clinically presumed diagnosis...

  13. Diagnostic value of enzyme linked immuno-sorbent assay for cytomegalovirus disease.

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    Priya K

    2002-07-01

    Full Text Available BACKGROUND: Since interpretation of results of enzyme linked immuno-sorbent assay (ELISA for diagnosis of Cytomegalovirus (CMV infection in India is difficult, its diagnostic value required evaluation. AIMS: To evaluate the diagnostic value of ELISA against polymerase chain reaction (PCR in CMV disease. SETTINGS AND DESIGN: Results of ELISA test for CMV antibodies in CMV-DNA PCR positive and negative patients and normal healthy blood donors were analysed. METHODS AND MATERIAL: Anti-CMV antibodies were assayed by ELISA on the sera of 26 CMV PCR positive and 21 PCR negative patients and 35 normal healthy blood donors. STATISTICAL ANALYSIS: Chi square and Fischer exact test were used for statistical analysis. RESULTS: Anti-CMV antibodies (IgG or IgG and IgM were present in 20 (76.9% of 26 PCR positive and 13 (61.9% of 21 PCR negative patients. ELISA was negative in six (23.1% of 26 PCR positive patients. Of the 28 paediatric patients, ELISA was positive in 14 (73.7% of 19 PCR positive and three (33.3% of nine PCR negative patients showing a statistically significant difference (Chi square test, P value 0.038. Among the 19 patients having complications after organ transplant, ELISA showed anti-CMV antibodies in six (85.7% of seven PCR positive and 11 (91.7% of 12 PCR negative patients showing no significant difference. CMV-DNA was not detected in the buffy coat of 35 sero-positive blood donors. CONCLUSION: ELISA has no diagnostic value in the detection of CMV activation although it may help in the differential diagnosis of CMV infection in the paediatric age group.

  14. Cytomegalovirus IgM Seroprevalence among Women of Reproductive Age in the United States.

    Science.gov (United States)

    Wang, Chengbin; Dollard, Sheila C; Amin, Minal M; Bialek, Stephanie R

    2016-01-01

    Cytomegalovirus (CMV) IgM indicates recent active CMV infection. CMV IgM seroprevalence is a useful marker for prevalence of transmission. Using data from the National Health and Nutrition Examination Survey (NHANES) III 1988-1994, we present estimates of CMV IgM prevalence by race/ethnicity, provide a comparison of IgM seroprevalence among all women and among CMV IgG positive women, and explore factors possibly associated with IgM seroprevalence, including socioeconomic status and exposure to young children. There was no difference in IgM seroprevalence by race/ethnicity among all women (3.1%, 2.2%, and 1.6% for non-Hispanic white, non-Hispanic black and Mexican American, respectively; P = 0.11). CMV IgM seroprevalence decreased significantly with increasing age in non-Hispanic black women (Pwomen (P = 0.07), while no apparent trend with age was seen in non-Hispanic white women (P = 0.99). Among 4001 IgG+ women, 118 were IgM+, resulting in 4.9% IgM seroprevalence. In IgG+ women, IgM seroprevalence varied significantly by age (5.3%, 7.3%, and 3.7% for women of 12-19, 20-29, and 30-49 years; P = 0.04) and race/ethnicity (6.1%, 2.7%, and 2.0% for non-Hispanic white, non-Hispanic black, and Mexican American; P<0.001). The factors reported associated with IgG seroprevalence were not associated with IgM seroprevalence. The patterns of CMV IgM seroprevalence by age, race/ethnicity, and IgG serostatus may help understanding the epidemiology of congenital CMV infection as a consequence of vertical transmission and are useful for identifying target populations for intervention to reduce CMV transmission.

  15. Seroprevalence to cytomegalovirus in the Portuguese population, 2002-2003.

    Science.gov (United States)

    Lopo, S; Vinagre, E; Palminha, P; Paixao, M T; Nogueira, P; Freitas, M G

    2011-01-01

    The prevalence of cytomegalovirus (CMV) infections ranges between 50% and 85% in adults in the United States, and its epidemiology varies in different regions of the world and between socioeconomic and age groups. In Portugal, no study has been carried out to date to determine the prevalence of CMV in the general population. Under the second National Serological Survey conducted in continental Portugal in 2001–2002, we estimated the prevalence of individuals with antibodies to CMV using indirect immunofluorescence to detect virus-specific IgG. The population sample included 2,143 individuals of both sexes and different ages from all 18 districts in Portugal. The national seroprevalence of CMV was determined as 77%. We analysed the proportion of CMV IgG by sex, age group and district of residence. This was the first nationally representative study of seroprevalence of CMV in Portugal. The results of the study indicate that CMV infection is highly prevalent in the population and occurs mainly in the first years of life. PMID:21722611

  16. Serologic survey of cytomegalovirus and rubella virus in Tabriz, Iran

    Institute of Scientific and Technical Information of China (English)

    Samad Farhadi; Farnaz Faraji; Elnaz Babaei; Hamid Reza Lotfi; Nader Hajizadeh; Hakimeh Rasoolian

    2015-01-01

    Objective:To determine the prevalence of rubella and cytomegalovirus (CMV) among women in Tabriz City, Iran in 2013. Methods: This study was carried out in numerous laboratories in city of Tabriz. In 2013, 26 618 women aged 18–35 years were enrolled in this study. Serum samples were analyzed with chemiluminescence apparatus andSPSS software was used to conduct the statistical analysis. Results:A total of 26 618 individuals were examined (10 598 cases for anti-CMV and 16 020 cases for anti-rubella). About 98.9% and 1.1% samples were reported positive and negative for CMV immunoglobulin G (IgG), respectively. The positivity for anti-CMV immunoglobulin M (IgM) antibody was found in 0.75% samples, while 99.25% were negative for the anti-CMV IgM antibody. Anti-IgG against rubella seropositivity was found in 95.8% and rubella IgM seropositivity in 0.93%. Anti-IgG against rubella seronegativity was found in 4.2% and rubella IgM seronegativity in 99.07%. Conclusions: According to the results, primary and secondary infections are usually symptomless or inconspicuous, but they can cause serious fetal damage. Routine antenatal care should therefore include serological testing to check the immune status of the woman and to diagnose any fresh virus infections that may arise.

  17. The Role of The Cytomegalovirus Antigenemia Assay in the Detection and Prevention of Cytomegalovirus Syndrome and Disease in Solid Organ Transplant Recipients: A Review of the British Columbia Experience

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    Erica D Greanya

    2005-01-01

    Full Text Available BACKGROUND: The pp65 cytomegalovirus (CMV antigenemia assay has been used as a means of guiding the pre-emptive therapy of CMV disease in solid organ transplant (SOT recipients. Recently, concerns have been raised regarding the utility of the test to accurately and precisely detect viral activity early enough to reduce the morbidity and mortality associated with CMV.

  18. Macrophage Activation by Ursolic and Oleanolic Acids during Mycobacterial Infection

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    Sonia López-García

    2015-08-01

    Full Text Available Oleanolic (OA and ursolic acids (UA are triterpenes that are abundant in vegetables, fruits and medicinal plants. They have been described as active moieties in medicinal plants used for the treatment of tuberculosis. In this study, we analyzed the effects of these triterpenes on macrophages infected in vitro with Mycobacterium tuberculosis (MTB. We evaluated production of nitric oxide (NO, reactive oxygen species (ROS, and cytokines (TNF-α and TGF-β as well as expression of cell membrane receptors (TGR5 and CD36 in MTB-infected macrophages following treatment with OA and UA. Triterpenes caused reduced MTB growth in macrophages, stimulated production of NO and ROS in the early phase, stimulated TNF-α, suppressed TGF-β and caused over-expression of CD36and TGR5 receptors. Thus, our data suggest immunomodulatory properties of OA and UA on MTB infected macrophages. In conclusion, antimycobacterial effects induced by these triterpenes may be attributable to the conversion of macrophages from stage M2 (alternatively activated to M1 (classically activated.

  19. Incremental Cost Effectiveness of Prophylaxis for Cytomegalovirus Disease in Patients with AIDS

    OpenAIRE

    Kempen, John H.; Frick, Kevin D.; Jabs, Douglas A.

    2001-01-01

    Cytomegalovirus (CMV) disease, an opportunistic complication in patients with AIDS, causes substantial morbidity and has high treatment costs. Although prevention of this disease is highly desirable, incremental cost-effectiveness estimates for proposed prophylactic strategies in the era prior to the availability of highly active antiretroviral therapy (HAART) were unfavourable relative to other specific antimicrobial prophylactic strategies in patients with AIDS. With the availability of HAA...

  20. Immunization with Cytomegalovirus Envelope Glycoprotein M and Glycoprotein N DNA Vaccines can Provide Mice with Complete Protection against a Lethal Murine Cytomegalovirus Challenge

    Institute of Scientific and Technical Information of China (English)

    Huadong Wang; Yanfeng Yao; Chaoyang Huang; Quanjiao Chen; Jianjun Chen; Ze Chen

    2013-01-01

    Human cytomegalovirus virions contain three major glycoprotein complexes (gC Ⅰ,Ⅱ,Ⅲ),all of which are required for CMV infectivity.These complexes also represent major antigenic targets for anti-viral immune responses.The gC Ⅱ complex consists of two glycoproteins,gM and gN.In the current study,DNA vaccines expressing the murine cytomegalovirus (MCMV) homologs of the gM and gN proteins were evaluated for protection against lethal MCMV infection in a mouse model.Humoral and cellular immune responses,spleen viral titers,and mice survival and body-weight changes were examined.The results showed that immunization with gM or gN DNA vaccine alone was not able to offer good protection,whereas co-immunization with both gM and gN induced an effective neutralizing antibody response and cellular immune response,and provided mice with complete protection against a lethal MCMV challenge.This study provides the first in vivo evidence that the gC Ⅱ (gM-gN) complex may be able to serve as a protective subunit antigen for future HCMV vaccine development.

  1. Direct and Indirect Effects of Cytomegalovirus-induced gamma-delta T Cells after Kidney Transplantation

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    Lionel eCouzi

    2015-01-01

    Full Text Available Despite effective anti-viral therapies, cytomegalovirus (CMV is still associated with direct (CMV disease and indirect effects (rejection and poor graft survival in kidney transplant recipients. Recently, an unconventional T cell population (collectively designated as Vδ2neg γδ T cells has been characterized during the anti-CMV immune response in all solid-organ and bone-marrow transplant recipients, neonates, and healthy people. These CMV-induced γδ T cells undergo a dramatic and stable expansion after CMV infection, in a conventional ‘adaptive’ manner. Similarly as CMV-specific CD8+ αβ T cells, they exhibit an effector/memory TEMRA phenotype and cytotoxic effector functions. Activation of Vd2neg gd T cells by CMV-infected cells involves the TCR and still ill-defined co-stimulatory molecules such LFA-1. A multiple of Vd2neg gd TCR ligands are apparently recognized on CMV-infected cells, the first one identified being the MHC-related molecule endothelial protein C receptor (EPCR. A singularity of CMV-induced Vd2neg gd T cells is to acquire CD16 expression and to exert an antibody-dependent cell-mediated inhibition on CMV replication, which is controlled by a specific cytokine microenvironment. Beyond the well-demonstrated direct anti-CMV effect of Vδ2neg γδ T cells, unexpected indirect effects of these cells have been also observed in the context of kidney transplantation. CMV-induced Vδ2neg γδ T cells have been involved in surveillance of malignancy subsequent to long term immunosuppression. Moreover, CMV-induced CD16+ γδ T cells are cell effectors of antibody-mediated rejection of kidney transplants, and represent a new physiopathological contribution to the well-known association between CMV infection and poor graft survival. All these basic and clinical studies paved the road to the development of a future γδ T cell-based immunotherapy. In the meantime, γδ T cell monitoring should prove a valuable immunological

  2. Human Ebola virus infection results in substantial immune activation.

    Science.gov (United States)

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  3. Evaluation of Real-Time PCR Laboratory-Developed Tests Using Analyte-Specific Reagents for Cytomegalovirus Quantification▿

    OpenAIRE

    Caliendo, Angela M.; Ingersoll, Jessica; Fox-Canale, Andrea M.; Pargman, Sabine; Bythwood, Tameka; Hayden, Mary K.; Bremer, James W.; Lurain, Nell S.

    2007-01-01

    Viral load testing for cytomegalovirus (CMV) has become the standard for the diagnosis of infection and monitoring of therapy at many transplant centers. However, no viral load test has been approved by the FDA. Therefore, many laboratories rely on laboratory-developed assays. This study evaluated the performance characteristics of two real-time PCR tests developed using the artus CMV analyte-specific reagents (ASRs). One version is distributed by Abbott Molecular and the other by QIAGEN. For...

  4. Neonatal Neural Progenitor Cells and Their Neuronal and Glial Cell Derivatives Are Fully Permissive for Human Cytomegalovirus Infection▿

    OpenAIRE

    Luo, Min Hua; Philip H. Schwartz; Fortunato, Elizabeth A.

    2008-01-01

    Congenital human cytomegalovirus (HCMV) infection causes central nervous system structural abnormalities and functional disorders, affecting both astroglia and neurons with a pathogenesis that is only marginally understood. To better understand HCMV's interactions with such clinically important cell types, we utilized neural progenitor cells (NPCs) derived from neonatal autopsy tissue, which can be differentiated down either glial or neuronal pathways. Studies were performed using two viral i...

  5. A dominant role for the immunoproteasome in CD8+ T cell responses to murine cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Sarah Hutchinson

    Full Text Available Murine cytomegalovirus (MCMV is an important animal model of human cytomegalovirus (HCMV, a β-Herpesvirus that infects the majority of the world's population and causes disease in neonates and immunocompromised adults. CD8(+ T cells are a major part of the immune response to MCMV and HCMV. Processing of peptides for presentation to CD8(+ T cells may be critically dependent on the immunoproteasome, expression of which is affected by MCMV. However, the overall importance of the immunoproteasome in the generation of immunodominant peptides from MCMV is not known. We therefore examined the role of the immunoproteasome in stimulation of CD8(+ T cell responses to MCMV - both conventional memory responses and those undergoing long-term expansion or "inflation". We infected LMP7(-/- and C57BL/6 mice with MCMV or with newly-generated recombinant vaccinia viruses (rVVs encoding the immunodominant MCMV protein M45 in either full-length or epitope-only minigene form. We analysed CD8(+ T cell responses using intracellular cytokine stain (ICS and MHC Class I tetramer staining for a panel of MCMV-derived epitopes. We showed a critical role for immunoproteasome in MCMV affecting all epitopes studied. Interestingly we found that memory "inflating" epitopes demonstrate reduced immunoproteasome dependence compared to non-inflating epitopes. M45-specific responses induced by rVVs remain immunoproteasome-dependent. These results help to define a critical restriction point for CD8(+ T cell epitopes in natural cytomegalovirus (CMV infection and potentially in vaccine strategies against this and other viruses.

  6. Serological diagnosis of infection with human herpesvirus type 6.

    OpenAIRE

    Irving, W L; Cunningham, A L

    1990-01-01

    OBJECTIVE--To identify clinical consequences of acute human herpesvirus type 6 infection by hypothesising that the virus will induce similar clinical syndromes to cytomegalovirus. DESIGN--Examination of consecutive serum samples from patients with illnesses compatible with acute cytomegalovirus infection or exanthem subitum by indirect immunofluorescence for the presence of antibodies to human herpesvirus type 6. An IgG absorption step was included to avoid false positive and negative results...

  7. Biliary scintigraphy in neonatal cytomegalovirus cholestasis

    International Nuclear Information System (INIS)

    Diagnostic value of hepatobiliary scintigraphy using mebrofenin-Te-99m was assessed in three newborns with cytomegalovirus (CMV) hepatitis and one baby with hepatitis B jaundice. All cases were affected by persistent jaundice with predominately conjugated bilirubin, alcoholic stools, anemia. One of this newborns (case number 1) was suspected of having biliary atresia due to the absence of intestinal excretion of the tracer. After three weeks intestinal passage was seen in scintiscan late after 24 h. Hepatobiliary scintigraphy represents a non-invasive diagnostic procedure which enables the detection of permeability of the biliary tract. (Author)

  8. RT-qPCR-based microneutralization assay for human cytomegalovirus using fibroblasts and epithelial cells.

    Science.gov (United States)

    Wang, Xiao; Peden, Keith; Murata, Haruhiko

    2015-12-16

    Human cytomegalovirus (HCMV) is a leading cause of congenital infection that can result in serious disabilities in affected children. To facilitate HCMV vaccine development, a microscale neutralization assay based on reverse transcription quantitative PCR (RT-qPCR) was developed to quantify HCMV-neutralizing antibodies. Our approach relies on the generation of crude lysates from virus-infected cells that are amenable to direct analysis by RT-qPCR, thereby circumventing rate-limiting procedures associated with sample RNA extraction and purification. By serial passaging of the laboratory HCMV strain AD169 in epithelial cells (ARPE-19), a revertant virus with restored epithelial cell tropism, designated AD169(wt131), was obtained. AD169 and AD169(wt131) were evaluated in both epithelial cells (ARPE-19) and fibroblasts (MRC-5) by one-step RT-qPCR targeting the immediate-early gene IE1 transcript of HCMV. Expression kinetics indicated that RT-qPCR assessment could be conducted as early as 6h post-infection. Human serum samples (n=30) from healthy donors were tested for HCMV-specific IgG using a commercially available ELISA and for HCMV-neutralizing activity using our RT-qPCR-based neutralization assay. In agreement with the ELISA results, higher neutralizing activity was observed in the HCMV IgG seropositive group when compared with the HCMV IgG seronegative group. In addition, HCMV IgG seropositive human sera exhibited higher neutralizing titers using epithelial cells compared with using fibroblasts (geometric mean titers of 344 and 8 in ARPE-19 cells and MRC-5 cells, respectively). Our assay was robust to variation in input virus dose. In addition, a simple lysis buffer containing a non-ionic detergent was successfully demonstrated to be a less costly alternative to commercial reagents for cell-lysate preparation. Thus, our rapid HCMV neutralization assay may be a straightforward and flexible high-throughput tool for measuring antibody responses induced by vaccination

  9. Neglected infections of poverty in the United States of America.

    Science.gov (United States)

    Hotez, Peter J

    2008-01-01

    In the United States, there is a largely hidden burden of diseases caused by a group of chronic and debilitating parasitic, bacterial, and congenital infections known as the neglected infections of poverty. Like their neglected tropical disease counterparts in developing countries, the neglected infections of poverty in the US disproportionately affect impoverished and under-represented minority populations. The major neglected infections include the helminth infections, toxocariasis, strongyloidiasis, ascariasis, and cysticercosis; the intestinal protozoan infection trichomoniasis; some zoonotic bacterial infections, including leptospirosis; the vector-borne infections Chagas disease, leishmaniasis, trench fever, and dengue fever; and the congenital infections cytomegalovirus (CMV), toxoplasmosis, and syphilis. These diseases occur predominantly in people of color living in the Mississippi Delta and elsewhere in the American South, in disadvantaged urban areas, and in the US-Mexico borderlands, as well as in certain immigrant populations and disadvantaged white populations living in Appalachia. Preliminary disease burden estimates of the neglected infections of poverty indicate that tens of thousands, or in some cases, hundreds of thousands of poor Americans harbor these chronic infections, which represent some of the greatest health disparities in the United States. Specific policy recommendations include active surveillance (including newborn screening) to ascertain accurate population-based estimates of disease burden; epidemiological studies to determine the extent of autochthonous transmission of Chagas disease and other infections; mass or targeted treatments; vector control; and research and development for new control tools including improved diagnostics and accelerated development of a vaccine to prevent congenital CMV infection and congenital toxoplasmosis. PMID:18575621

  10. Cytomegalovirus pp65 limits dissemination but is dispensable for persistence

    Energy Technology Data Exchange (ETDEWEB)

    Malouli, Daniel; Hansen, Scott G.; Nakayasu, Ernesto S.; Marshall, Emily E.; Hughes, Colette M.; Ventura, Abigail B.; Gilbride, Roxanne M.; Lewis, Matthew S.; Xu, Guangwu; Kreklywich, Craig; Whizin, Nathan; Fischer, Miranda; Legasse, Alfred W.; Viswanathan, Kasinath; Siess, Don; Camp, David G.; Axthelm, Michael K.; Kahl, Christoph; DeFilippis, Victor R.; Smith, Richard D.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus

    2014-04-01

    The tegument phosphoprotein pp65 (UL83) is the most abundant virion protein in human cytomegalovirus (HCMV). Since pp65 is immunodominant in persistently infected individuals, subunit vaccines against HCMV often include pp65 as T cell stimulatory component. Although HCMV pp65 is non-essential for viral growth in vitro it is thought to have an important role in primary and persistent infection since pp65 displays multiple immunomodulatory functions. To determine whether pp65 is required for infection and to evaluate its role in natural and vaccination-induced immunity we generated a rhesus CMV lacking both homologues, pp65a (Rh111) and pp65b (Rh112). Lack of pp65 resulted in a slight growth defect in vitro and an increase of defective particle formation. However, most pp65-deleted virions in the supernatant were phenotypically normal and proteomics analysis revealed that the ratios of the remaining viral proteins were largely unchanged. RhCMV Δpp65ab was able to persistently infect CMV-negative rhesus macaques (RM) and to super-infect RM previously infected with CMV. To determine whether T cells against pp65 are essential for protection against CMV, we challenged Δpp65ab-infected animals with RhCMV ΔUS2-11, a viral recombinant that lacks inhibitors of MHC-I antigen presentation and is thus unable to overcome CMV-specific T cell immunity. Despite a complete lack of pp65-specific T cells, Δpp65ab protected against ΔUS2-11 challenge suggesting that pp65-specific T cells are not essential for T cell immunity against CMV. Using the same approach we further demonstrate that pp65b-specific T cells, induced by heterologous prime/boost vaccination, are not sufficient to protect against ΔUS2-11 challenge. Our data provides a new approach to test the efficacy of subunit vaccine candidates and suggest that pp65 vaccines are insufficient to induce a T cell response that recapitulates the protective effect of natural infection.

  11. Cytomegalovirus pneumonia in a patient with interstitial pneumonia and Nocardia asiatica presenting as cavitary lung lesions.

    Science.gov (United States)

    Saraya, Takeshi; Ohkuma, Kosuke; Kikuchi, Ken; Tamura, Masaki; Honda, Kojiro; Yamada, Atsuko; Araki, Koji; Ishii, Haruyuki; Makino, Hiroshi; Takei, Hidefumi; Karita, Shin; Fujiwara, Masachika; Takizawa, Hajime; Goto, Hajime

    2013-01-01

    A 66-year-old man who suffered from an acute exacerbation of interstitial pneumonia developed a cavitary lesion after taking immunosuppressive drugs. He was diagnosed with cytomegalovirus (CMV) pneumonia. CMV was not thought to be the underlying cause of the cavitary lung lesions, as only six cases have been described thus far. However, this case clearly demonstrates that the development of cavitary lung lesions can be caused by CMV. Following CMV pneumonia, cavitary lesions again occurred in the patient's lungs that were thought to be the first case of cavitary lesions caused by Nocardia asiatica infection. PMID:23448771

  12. Celulitis por citomegalovirus Cytomegalovirus cellulitis

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    A. Ruiz Lascano

    2002-12-01

    Full Text Available Las lesiones cutáneas por citomegalovirus (CMV son infrecuentes y a menudo una manifestación tardía de una enfermedad sistémica, que generalmente anuncia un curso fatal. Comunicamos un caso de celulitis por CMV: una mujer de 70 años con trasplante renal efectuado 1 mes antes de la consulta, terapia inmunosupresora con ciclosporina A y metilprednisona. La paciente ingresó por fiebre, dolor e impotencia funcional en pierna derecha. Comprobamos la existencia de una placa de 8 por 4 cm eritematoedematosa. La tratamos con antibióticos sin mejoría, por lo que realizamos un estudio histopatológico de piel que mostró cambios citopáticos compatibles con infección por CMV. Los cultivos bacteriológicos y micológicos fueron negativos. La inmunohistoquímica específica para CMV y el estudio de reacción en cadena de la polimerasa (PCR de la biopsia de piel fueron positivas, al igual que la antigenemia. El tratamiento con ganciclovir produjo la mejoría del cuadro clínico. En la literatura revisada no hemos encontrado la celulitis como manifestación de enfermedad cutánea por CMV.Cutaneous lesions in CMV infection are rare, often a late manifestation of systemic infection, and usually herald a fatal course. A 70 year-old woman received a kidney transplantation one month before consulting and immunosuppressive therapy that included cyclosporine A and methylprednisone. She complained of fever, local pain in her right leg, and an erythematous and swelling plaque. She was treated with intravenous antibiotics without improvement. A skin biopsy was performed and the tissue obtained was sent for bacterial and fungal cultures as well as for histological examination. Cultures were negative. The biopsy showed CMV cytopathic changes. Immunoperoxidase staining was positive for CMV and polymerase chain reaction (PCR testing revealed CMV DNA. She was treated with ganciclovir with resolution of the lesion. CMV cellulitis is a rare cutaneous manifestation

  13. Report from the second cytomegalovirus and immunosenescence workshop

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    Wills Mark

    2011-10-01

    Full Text Available Abstract The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.

  14. Natural killer cells regulate murine cytomegalovirus-induced sialadenitis and salivary gland disease.

    Science.gov (United States)

    Carroll, Virginia A; Lundgren, Alyssa; Wei, Hairong; Sainz, Susan; Tung, Kenneth S; Brown, Michael G

    2012-02-01

    The transmission of herpesviruses depends on viral shedding at mucosal surfaces. The salivary gland represents a major site of persistent viral replication for many viruses, including cytomegalovirus. We established a mouse model of salivary gland dysfunction after acute viral infection and investigated the cellular requirements for the loss of secretion. Murine cytomegalovirus (MCMV) infection severely impaired saliva secretion independently of salivary gland virus levels. Lymphocytes or circulating monocytes/macrophages were not required for secretory dysfunction. Dysfunction occurred before glandular inflammation, suggesting that a soluble mediator initiated the disruption of acinar cell function. Despite genetic differences in innate resistance to MCMV, NK cells protected the host against acinar atrophy and the loss of secretions under conditions of an exceedingly low virus inoculum. NK cells also modulated the type of glandular inflammation after infection, as they prevented an influx of Siglec-F(+) polymorphonuclear leukocytes (PMNs). Therefore, beyond their recognized role in controlling MCMV replication, NK cells preserve organ integrity and function and regulate the innate inflammatory response within the gland.

  15. Utilizing a TLR5-Adjuvanted Cytomegalovirus as a Lentiviral Vaccine in the Nonhuman Primate Model for AIDS.

    Directory of Open Access Journals (Sweden)

    Jesse D Deere

    Full Text Available Despite tremendous progress in our understanding of human immunodeficiency virus (HIV natural history and advances in HIV treatment, there is neither an approved vaccine nor a cure for infection. Here, we describe the development and characterization of a novel replicating vaccine vector utilizing Cytomegalovirus (CMV and a TLR5 adjuvant. After partial truncation of the central, immunodominant hypervariable domain, flagellin (fliC from Salmonella was cloned downstream of a codon optimized gag gene from simian immunodeficiency virus (SIV and transiently expressed in telomerized rhesus fibroblast (TeloRF cells in culture. Lysates generated from these transfected cells induced the tumor necrosis factor alpha (TNF-α, in a mouse macrophage cell line, in a TLR5-dependent manner. The Gag/FliC expression construct was cloned into a bacterial artificial chromosome encoding the rhesus CMV (RhCMV genome, and infectious RhCMV was generated following transfection of TeloRF cells. This virus stably expressed an SIV Gag/FliC fusion protein through four serial passages. Lysates generated from infected cells induced TNF-α in a TLR5-dependent manner. Western blot analysis of infected cell lysates verified expression of a Gag/FliC fusion protein using a SIV p27 capsid monoclonal antibody. Lastly, rhesus macaques inoculated with this novel RhCMV virus demonstrated increased inflammatory responses at the site of inoculation seven days post-infection when compared to the parental RhCMV. These results demonstrate that an artificially constructed replicating RhCMV expressing an SIV Gag/FliC fusion protein is capable of activating TLR5 in a macrophage cell line in vitro and induction of an altered inflammatory response in vivo. Ongoing animals studies are aimed at determining vaccine efficacy, including subsequent challenge with pathogenic SIV.

  16. Killer-cell immunoglobulin-like receptors and cytomegalovirus reactivation during late pregnancy.

    Science.gov (United States)

    Alvarado-Hernández, D L; Benítez-Sánchez, A; Rodríguez-Cuevas, J S; Rosales-Saavedra, T; Guerra-Palomares, S E; Comas-García, A; Noyola, D E; García-Sepúlveda, C A

    2016-08-01

    Human cytomegalovirus (CMV) represents an important public health concern as it is associated with severe morbidity and mortality in transplant recipients, HIV-infected individuals and pregnant women given the risk of congenital infection. Congenital CMV is a leading cause of neurological sequelae, developmental delay and birth defects worldwide. Cytomegalovirus can be transmitted to the foetus following maternal infection or reactivation. NK cells expressing killer-cell immunoglobulin-like receptors (KIR) are part of the innate immune system and the first line of defence against viral incursions. Previous reports have shown that KIR genes are associated with CMV infections in the post-transplant setting. In this study, we set out to determine whether a protective effect of KIR genes over CMV infection is seen in Mexican pregnant women. Cytomegalovirus infection was assessed through nucleic acid testing in 200 pregnant women and 600 healthy blood donors comprising the Mexican mestizo reference population. Killer-cell immunoglobulin-like receptors and HLA-C genotypes were obtained from 200 pregnant women and 300 reference samples using a comprehensive PCR-SSP approach. We observed statistically lower carrier frequencies of cB03|tA01 gene-content haplotype, of cB03 haplotype motif, of the KIR2DL5 + 2DS3/2DS5 gene pair and of KIR2DL5 amongst CMV-positive pregnant women in comparison with those CMV negative. None of these were associated with CMV status in the reference population. Logistic regression analysis revealed that the most important factor determining CMV status during third-trimester pregnancies was the KIR2DL5 + 2DS3/2DS5 gene pair (OR 0.376 (95%CI 0.174, 0.811, P = 0.013). Our results indicate that CMV-protective KIR gene associations described in Caucasoid populations are also present in the genetically distinct Mexican mestizo population. Our results suggest that certain KIR gene combinations provide protection against CMV infections occurring

  17. Drug Repurposing Approach Identifies Inhibitors of the Prototypic Viral Transcription Factor IE2 that Block Human Cytomegalovirus Replication.

    Science.gov (United States)

    Mercorelli, Beatrice; Luganini, Anna; Nannetti, Giulio; Tabarrini, Oriana; Palù, Giorgio; Gribaudo, Giorgio; Loregian, Arianna

    2016-03-17

    New targets for antiviral strategies are needed against human cytomegalovirus (HCMV), a major human pathogen. A cell-based screen aimed at finding inhibitors of the viral transcription factor Immediate-Early 2 (IE2) was performed in HCMV-infected cells expressing EGFP under the control of an IE2-inducible viral promoter. Screening of a library of bioactive small molecules led to the identification of several compounds able to inhibit EGFP expression and also HCMV replication with potency in the low-micromolar range. Follow-up studies with four selected hits indicated that they all block viral DNA synthesis as well as viral Early and Late gene expression. Furthermore, mechanistic studies confirmed that the compounds specifically act via inhibition of IE2 transactivating activity, thus blocking viral Early gene expression and the progression of virus replication. These results provide proof of concept for identifying small molecules that modulate the activity of a microbial transcription factor to control pathogen replication. PMID:26877023

  18. "Aspergillosis following Cytomegalovirus disease in a kidney transplant patient "

    Directory of Open Access Journals (Sweden)

    "Ameri Sh

    2003-06-01

    Full Text Available A 32-year-old end stage renal disease (ESRD woman was scheduled for transplantation. Also, she has had fever of unknown origin (FUO, rise of ESR and PPD>22 mm. Therefore treatment with isoniazid and rifampin was started three months prior to transplantation. She developed allograft dysfunction on week after transplantation. She received a few course pulse therapy (methyl prednisolone, antilymphocyte globulin (ALG, hemodialysis and because of low blood level of cyclosporine, isoniazid and rifampin were stopped. She was seen because of unilateral decreased vision, fever, cough and in physical examination, chorioretinitis and bilateral infiltration in both lungs were seen three weeks later. Severe cytomegalovirus (CMV antigenemia was detected and she responded rapidly to gancyclovir. One month later, she complained of fever and productive cough again. In chest X-ray (CXR, cavitary lesions were shown and with transthoracic biopsy, invasive aspergillosis was detected. In spite of amphotericin B therapy, she developed CNs involvement. Unfortunately she expired six months post transplantation. This is an interesting case of aspergillosis following CMV infection most likely because of an excess of immunosuppression.

  19. CYTOMEGALOVIRUS INTERSTITIAL PNEUMONITIS FOLLOWING ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    XU Xiao-hua; HUANG Lian-sheng; ZHANG Xiao-hong; ZHU Kang-er; XU Yang; WU Dong; ZHAO Xiao-ying

    2005-01-01

    Objective: To explore the risk factors and prophylaxis and treatment of cytomegalovirus interstitial pneumonitis(CMV-IP) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: 43 patients who received allo-PBSCT were allocated to either a Gancyclovir(GCV)-prophylaxis group (n=19) or a non-GCV prophylaxis group (n=24).A comparison was made of the incidence of CMV-IP in patients given or not given prophylactic gancyclovir. Results: 9patients in non-GCV prophylaxis group developed late CMV-IP (P<0.05). Graft-versus-host-disease (GVHD) may be associated with a high risk of CMV-IP. 5 cases of CMV-IP were successfully treated with GCV, but 3 cases died of CMV-IP.The most common adverse event of GCV was neutropenia, but was reversible. Conclusion: CMV infection was a major cause of interstitial pneumonitis after allo-PBSCT, which correlated strongly with the severity of GVHD. Gancyclovir was shown to be effective in both prophylaxis and treatment of CMV-IP.

  20. Cytomegalovirus and Epstein-Barr virus in breast cancer.

    Directory of Open Access Journals (Sweden)

    Ann K Richardson

    Full Text Available Findings of polymerase chain reaction (PCR studies of cytomegalovirus (CMV and Epstein-Barr virus (EBV and breast cancer vary, making it difficult to determine whether either, both, or neither virus is causally associated with breast cancer. We investigated CMV and EBV in paired samples of breast cancer and normal breast tissue from 70 women using quantitative PCR. A serum sample from each woman was tested for CMV and EBV IgG. To place our results in context, we reviewed the existing literature and performed a meta-analysis of our results together with previous PCR studies of EBV, CMV, and breast cancer. Of the serology samples, 67 of 70 (96% were EBV IgG positive and 49 of 70 (70% were CMV IgG positive. QPCR detected EBV in 24 (34% of the tumour and 9 (13% of the paired normal specimens and CMV in 0 (0% of the tumour and 2 (3% of the paired normal specimens. Our findings, together with earlier results summarised in the meta-analysis, suggest several possibilities: variable findings may be due to limitations of molecular analyses; 'hit and run' oncogenesis may lead to inconsistent results; one or both viruses has a role at a later stage in breast cancer development; infection with multiple viruses increases breast cancer risk; or neither virus has a role. Future studies should focus on ways to investigate these possibilities, and should include comparisons of breast cancer tissue samples with appropriate normal tissue samples.

  1. BST2/Tetherin enhances entry of human cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Kasinath Viswanathan

    2011-11-01

    Full Text Available Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV, indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV.

  2. Ganciclovir sensitivity of cytomegalovirus at diagnosis and during treatment of cytomegalovirus pneumonia in marrow transplant recipients.

    OpenAIRE

    Slavin, M A; Bindra, R R; Gleaves, C A; Pettinger, M. B.; Bowden, R A

    1993-01-01

    Cytomegalovirus (CMV) often persists in the lungs of marrow transplant patients with CMV pneumonia, despite ganciclovir (GCV) treatment. To determine whether GCV resistance contributes to viral persistence, the susceptibilities of CMV isolates from diagnostic bronchoalveolar lavage samples and CMV isolates obtained during treatment or from autopsy lung tissue from 12 patients were compared by DNA hybridization. Resistance (50% effective dose, > 12 microM) was detected in an isolate from only ...

  3. Cytomegalovirus as a cause of anterior uveitis in immunocompetent patients

    NARCIS (Netherlands)

    van Boxtel, Lonneke A. A.; van der Lelij, Allegonda; van der Meer, Johannes; Los, Leonoor I.

    2007-01-01

    Purpose: To describe 7 cases of unilateral, chronic and/or recurrent anterior uveitis caused by cytomegalovirus (CMV) in immunocompetent patients; to identify specific ophthalmologic characteristics; and to evaluate the clinical effect of valganciclovir treatment. Design: Retrospective observational

  4. Mutual Interference between Cytomegalovirus and Reconstitution of Protective Immunity after Hematopoietic Cell Transplantation

    Science.gov (United States)

    Reddehase, Matthias J.

    2016-01-01

    Hematopoietic cell transplantation (HCT) is a therapy option for aggressive forms of hematopoietic malignancies that are resistant to standard antitumoral therapies. Hematoablative treatment preceding HCT, however, opens a “window of opportunity” for latent Cytomegalovirus (CMV) by releasing it from immune control with the consequence of reactivation of productive viral gene expression and recurrence of infectious virus. A “window of opportunity” for the virus represents a “window of risk” for the patient. In the interim between HCT and reconstitution of antiviral immunity, primarily mediated by CD8+ T cells, initially low amounts of reactivated virus can expand exponentially, disseminate to essentially all organs, and cause multiple organ CMV disease, with interstitial pneumonia (CMV-IP) representing the most severe clinical manifestation. Here, I will review predictions originally made in the mouse model of experimental HCT and murine CMV infection, some of which have already paved the way to translational preclinical research and promising clinical trials of a preemptive cytoimmunotherapy of human CMV disease. Specifically, the mouse model has been pivotal in providing “proof of concept” for preventing CMV disease after HCT by adoptive transfer of preselected, virus epitope-specific effector and memory CD8+ T cells bridging the critical interim. However, CMV is not a “passive antigen” but is a pathogen that actively interferes with the reconstitution of protective immunity by infecting bone marrow (BM) stromal cells that otherwise form niches for hematopoiesis by providing the structural microenvironment and by producing hematopoietically active cytokines, the hemopoietins. Depending on the precise conditions of HCT, reduced homing of transplanted hematopoietic stem- and progenitor cells to infected BM stroma and impaired colony growth and lineage differentiation can lead to “graft failure.” In consequence, uncontrolled virus spread

  5. Mutual Interference between Cytomegalovirus and Reconstitution of Protective Immunity after Hematopoietic Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Matthias J. Reddehase

    2016-08-01

    Full Text Available Hematopoietic cell transplantation (HCT is a therapy option for aggressive forms of hematopoietic malignancies that are resistant to standard antitumoral therapies. Hematoablative treatment preceding HCT, however, opens a ‘window of opportunity’ for latent cytomegalovirus (CMV by releasing it from immune control with the consequence of reactivation of productive viral gene expression and recurrence of infectious virus. A ‘window of opportunity’ for the virus represents a ‘window of risk’ for the patient. In the interim between HCT and reconstitution of antiviral immunity, primarily mediated by CD8+ T cells, initially low amounts of reactivated virus can expand exponentially, disseminate to essentially all organs, and cause multiple organ CMV disease, with interstitial pneumonia (CMV-IP representing the most severe clinical manifestation. Here I will review predictions originally made in the mouse model of experimental HCT and murine CMV infection, some of which have already paved the way to translational preclinical research and promising clinical trials of a pre-emptive cytoimmunotherapy of human CMV disease. Specifically, the mouse model has been pivotal in providing ‘proof of concept’ for preventing CMV disease after HCT by adoptive transfer of preselected, virus epitope-specific effector and memory CD8+ T cells bridging the critical interim. CMV, however, is not a ‘passive antigen’ but is a pathogen that actively interferes with the reconstitution of protective immunity by infecting bone marrow stromal cells that otherwise form niches for hematopoiesis by providing the structural microenvironment and by producing hematopoietically active cytokines, the hemopoietins. Depending on the precise conditions of HCT, reduced homing of transplanted hematopoietic stem- and progenitor cells to infected bone marrow stroma and impaired colony growth and lineage differentiation can lead to ‘graft failure’. In consequence

  6. Infection

    Science.gov (United States)

    ... Potential Hazards Exposure of employees to community and nosocomial infections, e.g., Methicillin-resistant Staphylococcus aureus (MRSA) . Nosocomial infections are infections that occur from exposure to infectious ...

  7. Comparison of several fixation methods for cytomegalovirus antigenemia assay.

    OpenAIRE

    Pérez, J.L.; De Oña, M; Niubò, J; Villar, H.; Melón, S.; García, A.; Martín, R.

    1995-01-01

    Two fixation methods based on formaldehyde or acetone for qualitative cytomegalovirus antigenemia assay were evaluated on 405 consecutive blood samples. Cytomegalovirus was detected in 40 samples by the antigenemia assay: 36 were detected by formaldehyde fixation; 22, by acetone; and 18, by both methods. Differences were statistically significant (P = 0.0043). In addition, four fixation methods (two based on formalin [with and without permeabilization] and two using acetone at different fixat...

  8. Platelets, acting in part via P-selectin, mediate cytomegalovirus-induced microvascular dysfunction.

    Science.gov (United States)

    Khoretonenko, Mikhail V; Brunson, Jerry L; Senchenkov, Evgeny; Leskov, Igor L; Marks, Christian R; Stokes, Karen Y

    2014-12-15

    Cytomegalovirus (CMV) infects a majority of the population worldwide. It has been implicated in cardiovascular disease, induces microvascular dysfunction, and synergizes with hypercholesterolemia to promote leukocyte and platelet recruitment in venules. Although platelets and platelet-associated P-selectin contribute to cardiovascular disease inflammation, their role in CMV-induced vascular responses is unknown. We assessed the role of platelets in CMV-induced microvascular dysfunction by depleting platelets and developing bone marrow chimeric mice deficient in platelet P-selectin. Wild-type and chimeric mice received mock or murine (m)CMV intraperitoneally. Five weeks later, some mice were switched to a high-cholesterol diet (HC) to investigate the synergism between mCMV and HC. Arteriolar vasodilation and recruitment of leukocytes and donor platelets in venules were measured at 11wk. mCMV with or without HC caused significant endothelial dysfunction in arterioles. Platelet depletion restored normal vasodilation in mCMV-HC but not mCMV-ND mice, whereas protection was seen in both groups for platelet P-selectin chimeras. Only mCMV + HC elevated leukocyte and platelet recruitment in venules. Leukocyte adhesion was reduced to mock levels by acute platelet depletion but was only partially decreased in platelet P-selectin chimeras. Platelets from mCMV-HC mice and, to a lesser extent, mCMV-ND but not mock-HC mice showed significant adhesion in mCMV-HC recipients. Our findings implicate a role for platelets, acting through P-selectin, in CMV-induced arteriolar dysfunction and suggest that the addition of HC leads to a platelet-dependent, inflammatory infiltrate that is only partly platelet P-selectin dependent. CMV appeared to have a stronger activating influence than HC on platelets and may represent an additional therapeutic target in vulnerable patients.

  9. Case of cytomegalovirus colitis in an immunocompetent patient: a rare cause of abdominal pain and diarrhea in the elderly

    Directory of Open Access Journals (Sweden)

    Harano Y

    2015-03-01

    Full Text Available Yumi Harano, Lisa Kotajima, Hiroko Arioka Department of General Internal Medicine, St Luke's International Medical Center, Tokyo, Japan Abstract: Cytomegalovirus (CMV colitis usually occurs in immunocompromised patients after undergoing organ transplantation or chemotherapy. We report the case of a 60-year-old immunocompetent Japanese woman who presented with abdominal pain and bloody diarrhea. She was initially diagnosed as having ischemic colitis with pseudomembranous colitis on the basis of her symptoms, Clostridium difficile antigen positivity, and colonoscopic findings, which showed ulcer formation from the sigmoid colon to rectum. In spite of bowel rest and administration of metronidazole, her symptoms did not improve. On follow-up colonoscopy, ulcerations remained unchanged. Biopsy of the ulceration revealed CMV-infected cells leading to a diagnosis of CMV colitis. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients. We recommend endoscopic biopsy in a case of refractory abdominal pain and bloody diarrhea. Keywords: cytomegalovirus, colitis, immunocompetent, enterocolitis

  10. Cytomegalovirus and Langerhans Cell Histiocytosis: Is There a Link?

    Science.gov (United States)

    Khoddami, Maliheh; Nadji, Seyed-Alireza; Dehghanian, Paria; Vahdatinia, Mahsa; Shamshiri, Ahmad-Reza

    2016-01-01

    Background: Langerhans cell histiocytosis is a rare proliferative histiocytic disease of unknown etiology. Histologically, it is characterized by granuloma-like proliferation of Langerhans-type dendritic cells derived from bone marrow. Many investigators have suggested the possible role of viruses such as Epstein-Barr virus, human herpesvirus-6 (HHV-6), herpes simplex virus (HSV) types 1 and 2, and Cytomegalovirus in the pathogenesis of Langerhans cell histiocytosis. Objectives: In this study, we have investigated the presence of Cytomegalovirus in Langerhans cell histiocytosis in Iranian children. Patients and Methods: In this retrospective study, we have investigated the presence of Cytomegalovirus DNA expression, using paraffin-embedded tissue samples of 30 patients with Langerhans cell histiocytosis and 30 age and site-matched controls by qualitative Polymerase Chain Reaction (PCR) method. Results: No significant difference in prevalence of Cytomegalovirus presence between patients and controls was found. Cytomegalovirus was found by qualitative PCR in only 2 (6.66%) out of 30 patients and in 1 (3.3%) of 30 control samples with a P value of 1 (1.00 > 0.05) using chi-square test with OR: 2.07; 95% CI of OR: 0.18 - 24.15. Conclusions: Our findings do not support the hypothesis of a possible role for Cytomegalovirus in the pathogenesis of Langerhans cell histiocytosis. PMID:27307972

  11. Cytomegalovirus and Langerhans Cell Histiocytosis: Is There a Link?

    Directory of Open Access Journals (Sweden)

    Maliheh Khoddami

    2016-02-01

    Full Text Available Background: Langerhans cell histiocytosis is a rare proliferative histiocytic disease of unknown etiology. Histologically, it is characterized by granuloma-like proliferation of Langerhans-type dendritic cells derived from bone marrow. Many investigators have suggested the possible role of viruses such as Epstein-Barr virus, human herpesvirus-6 (HHV-6, herpes simplex virus (HSV types 1 and 2, and Cytomegalovirus in the pathogenesis of Langerhans cell histiocytosis. Objectives: In this study, we have investigated the presence of Cytomegalovirus in Langerhans cell histiocytosis in Iranian children. Patients and Methods: In this retrospective study, we have investigated the presence of Cytomegalovirus DNA expression, using paraffin-embedded tissue samples of 30 patients with Langerhans cell histiocytosis and 30 age and site-matched controls by qualitative Polymerase Chain Reaction (PCR method. Results: No significant difference in prevalence of Cytomegalovirus presence between patients and controls was found. Cytomegalovirus was found by qualitative PCR in only 2 (6.66% out of 30 patients and in 1 (3.3% of 30 control samples with a P value of 1 (1.00 > 0.05 using chi-square test with OR: 2.07; 95% CI of OR: 0.18 - 24.15. Conclusions: Our findings do not support the hypothesis of a possible role for Cytomegalovirus in the pathogenesis of Langerhans cell histiocytosis.

  12. Modulatory effect of rRNA synthesis and ppUL83 nucleolar compartmentalization on human cytomegalovirus gene expression in vitro.

    Science.gov (United States)

    Arcangeletti, Maria-Cristina; Rodighiero, Isabella; De Conto, Flora; Gatti, Rita; Orlandini, Guido; Ferraglia, Francesca; Motta, Federica; Covan, Silvia; Razin, Sergey V; Dettori, Giuseppe; Chezzi, Carlo

    2009-10-01

    The nucleolus is a nuclear domain involved in the biogenesis of ribosomes, as well as in many other important cellular regulatory activities, such as cell cycle control and mRNA processing. Many viruses, including herpesviruses, are known to exploit the nucleolar compartment during their replication cycle. In a previous study, we demonstrated the preferential targeting and accumulation of the human cytomegalovirus (HCMV) UL83 phosphoprotein (pp65) to the nucleolar compartment and, in particular, to the nucleolar matrix of lytically infected fibroblasts; such targeting was already evident at very early times after infection. Here we have investigated the possible effects of rRNA synthesis inhibition upon the development of HCMV lytic infection, by using either actinomycin D or cisplatin at low concentrations, that are known to selectively inhibit RNA polymerase I activity, whilst leaving RNA polymerase II function unaffected. Following the inhibition of rRNA synthesis by either of the agents used, we observed a significant redistribution of nucleolar proteins within the nucleoplasm and a simultaneous depletion of viral pp65 from the nucleolus; this effect was highly evident in both unextracted cells and in nuclear matrices in situ. Of particular interest, even a brief suppression of rRNA synthesis resulted in a very strong inhibition of the progression of HCMV infection, as was concluded from the absence of accumulation of HCMV major immediate-early proteins within the nucleus of infected cells. These data suggest that a functional relationship might exist between rRNA synthesis, pp65 localization to the nucleolar matrix and the normal development of HCMV lytic infection. PMID:19585527

  13. Malignant transformation of guinea pig cells after exposure to ultraviolet-irradiated guinea pig cytomegalovirus

    International Nuclear Information System (INIS)

    Guinea pig cells were malignantly transformed in vitro by ultraviolet (uv)-irradiated guinea pig cytomegalovirus (GPCMV). When guinea pig hepatocyte monolayers were infected with uv-irradiated GPCMV, three continuous epithelioid cell lines which grew in soft agarose were established. Two independently derived GPCMV-transformed liver cells and a cell line derived from a soft agarose clone of one of these lines induced invasive tumors when inoculated subcutaneously or intraperitoneally into nude mice. The tumors were sarcomas possibly derived from hepatic stroma or sinusoid. Transformed cell lines were also established after infection of guinea pig hepatocyte monolayers with human cytomegalovirus (HCMV) or simian virus 40 (SV40). These cell lines also formed colonies in soft agarose and induced sarcomas in nude mice. It is concluded that (i) GPCMV can malignantly transform guinea pig cells; (ii) cloning of GPCMV-transformed cells in soft agarose produced cells that induced tumors with a shorter latency period but with no alteration in growth rate or final tumor size; and (iii) the tumors produced by GPCMV-and HCMV-transformed guinea pig cells were more similar to each other in growth rate than to those induced by SV40-transformed guinea pig cells

  14. Crystal Structure of the Human Cytomegalovirus Glycoprotein B.

    Directory of Open Access Journals (Sweden)

    Heidi G Burke

    2015-10-01

    Full Text Available Human cytomegalovirus (HCMV, a dsDNA, enveloped virus, is a ubiquitous pathogen that establishes lifelong latent infections and caused disease in persons with compromised immune systems, e.g., organ transplant recipients or AIDS patients. HCMV is also a leading cause of congenital viral infections in newborns. Entry of HCMV into cells requires the conserved glycoprotein B (gB, thought to function as a fusogen and reported to bind signaling receptors. gB also elicits a strong immune response in humans and induces the production of neutralizing antibodies although most anti-gB Abs are non-neutralizing. Here, we report the crystal structure of the HCMV gB ectodomain determined to 3.6-Å resolution, which is the first atomic-level structure of any betaherpesvirus glycoprotein. The structure of HCMV gB resembles the postfusion structures of HSV-1 and EBV homologs, establishing it as a new member of the class III viral fusogens. Despite structural similarities, each gB has a unique domain arrangement, demonstrating structural plasticity of gB that may accommodate virus-specific functional requirements. The structure illustrates how extensive glycosylation of the gB ectodomain influences antibody recognition. Antigenic sites that elicit neutralizing antibodies are more heavily glycosylated than those that elicit non-neutralizing antibodies, which suggest that HCMV gB uses glycans to shield neutralizing epitopes while exposing non-neutralizing epitopes. This glycosylation pattern may have evolved to direct the immune response towards generation of non-neutralizing antibodies thus helping HCMV to avoid clearance. HCMV gB structure provides a starting point for elucidation of its antigenic and immunogenic properties and aid in the design of recombinant vaccines and monoclonal antibody therapies.

  15. The efficiency of human cytomegalovirus pp65(495-503) CD8+ T cell epitope generation is determined by the balanced activities of cytosolic and endoplasmic reticulum-resident peptidases.

    Science.gov (United States)

    Urban, Sabrina; Textoris-Taube, Kathrin; Reimann, Barbara; Janek, Katharina; Dannenberg, Tanja; Ebstein, Frédéric; Seifert, Christin; Zhao, Fang; Kessler, Jan H; Halenius, Anne; Henklein, Petra; Paschke, Julia; Cadel, Sandrine; Bernhard, Helga; Ossendorp, Ferry; Foulon, Thierry; Schadendorf, Dirk; Paschen, Annette; Seifert, Ulrike

    2012-07-15

    Control of human CMV (HCMV) infection depends on the cytotoxic activity of CD8(+) CTLs. The HCMV phosphoprotein (pp)65 is a major CTL target Ag and pp65(495-503) is an immunodominant CTL epitope in infected HLA-A*0201 individuals. As immunodominance is strongly determined by the surface abundance of the specific epitope, we asked for the components of the cellular Ag processing machinery determining the efficacy of pp65(495-503) generation, in particular, for the proteasome, cytosolic peptidases, and endoplasmic reticulum (ER)-resident peptidases. In vitro Ag processing experiments revealed that standard proteasomes and immunoproteasomes generate the minimal 9-mer peptide epitope as well as N-terminal elongated epitope precursors of different lengths. These peptides are largely degraded by the cytosolic peptidases leucine aminopeptidase and tripeptidyl peptidase II, as evidenced by increased pp65(495-503) epitope presentation after leucine aminopeptidase and tripeptidyl peptidase II knockdown. Additionally, with prolyl oligopeptidase and aminopeptidase B we identified two new Ag processing machinery components, which by destroying the pp65(495-503) epitope limit the availability of the specific peptide pool. In contrast to cytosolic peptidases, silencing of ER aminopeptidases 1 and 2 strongly impaired pp65(495-503)-specific T cell activation, indicating the importance of ER aminopeptidases in pp65(495-503) generation. Thus, cytosolic peptidases primarily interfere with the generation of the pp65(495-503) epitope, whereas ER-resident aminopeptidases enhance such generation. As a consequence, our experiments reveal that the combination of cytosolic and ER-resident peptidase activities strongly shape the pool of specific antigenic peptides and thus modulate MHC class I epitope presentation efficiency. PMID:22706083

  16. Glucocorticoids facilitate the transcription from the human cytomegalovirus major immediate early promoter in glucocorticoid receptor- and nuclear factor-I-like protein-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Inoue-Toyoda, Maki [Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575 (Japan); Kato, Kohsuke [Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575 (Japan); Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575 (Japan); Nagata, Kyosuke, E-mail: knagata@md.tsukuba.ac.jp [University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575 (Japan); Yoshikawa, Hiroyuki [Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575 (Japan); Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575 (Japan)

    2015-02-27

    Human cytomegalovirus (HCMV) is a common and usually asymptomatic virus agent in healthy individuals. Initiation of HCMV productive infection depends on expression of the major immediate early (MIE) genes. The transcription of HCMV MIE genes is regulated by a diverse set of transcription factors. It was previously reported that productive HCMV infection is triggered probably by elevation of the plasma hydroxycorticoid level. However, it is poorly understood whether the transcription of MIE genes is directly regulated by glucocorticoid. Here, we found that the dexamethasone (DEX), a synthetic glucocorticoid, facilitates the transcription of HCMV MIE genes through the MIE promoter and enhancer in a glucocorticoid receptor (GR)-dependent manner. By competitive EMSA and reporter assays, we revealed that an NF-I like protein is involved in DEX-mediated transcriptional activation of the MIE promoter. Thus, this study supports a notion that the increased level of hydroxycorticoid in the third trimester of pregnancy reactivates HCMV virus production from the latent state. - Highlights: • DEX facilitates the transcription from the HCMV MIE promoter. • GR is involved in DEX-dependent transcription from the HCMV MIE promoter. • A 17 bp repeat is responsible for the HCMV MIE promoter activation by DEX. • An NF-I-like protein is involved in the HCMV MIE promoter activation by DEX.

  17. 人乳头瘤病毒和单纯疱疹病毒2型及巨细胞病毒协同感染与子宫颈病变的关系%The co-infection of human papillomavirus, herpes simple virus-2 and cytomegalovirus in cervical diseases

    Institute of Scientific and Technical Information of China (English)

    叶峻杰; 马丽; 赵树华; 李俊杰; 杨丽娟

    2013-01-01

    目的 调查分析育龄妇女子宫颈上皮人乳头瘤病毒(HPV)感染情况,以及单纯疱疹病毒2型(HSV-2)、人巨细胞病毒(CMV)和HPV协同感染与宫颈癌前病变发展的关系.方法 本研究为前瞻性研究,将2010年1月至2011年3月期间,昆明市健康体检的育龄妇女2128名按年龄分组为18 ~ 24岁、25 ~ 34岁、35 ~ 49岁组,采用实时荧光定量PCR技术埘其宫颈标本HPV、HSV-2、CMVDNA检测感染情况及宫颈细胞学检查,采用SPSS 13.0软件进行统计分析.结果 18 ~49岁育龄妇女生殖道高危型人乳头瘤病毒(HR-HPV)、HSV-2、CMV感染率分别为11.04% (235/2128)、3.52%(75/2128)和5.26%(112/2128);不同宫颈病变HR-HPV的感染率:未出现异常细胞(NILM)为4.29% (82/1912),不明意义的不典型鳞状细胞(ASCUS)为55.93% (66/118),鳞状上皮内低度病变(LSIL)为84.62%(44/52),鳞状上皮内高度病变(HSIL)为93.19% (41/44),鳞状细胞癌(SCC)为2/2,感染率随宫颈癌前病变到宫颈癌发展而增加(r=0.644,P=0.000).各年龄组间HR-HPV、HSV-2感染率差异无统计学意义(x2 =2.979,P=0.226;x2=0.798,P=0.671);18 ~24岁组的CMV感染率(7.62%)最高,且感染率随着年龄增加而下降.HSV-2、HR-HPV双重感染率在细胞学异常组(3.24%,7/216)与细胞学正常组(2.41%,46/1912)之间差异无统计学意义(x2=0.557,P=0.455),HSV-2与HR-HPV感染无明显相关性(OR=0.56,95%CI:0.17 ~ 1.82),CMV感染与HR-HPV感染存在显著相关性(OR=3.14,95%CI:1.25~7.86).结论 HR-HPV感染是宫颈癌发生的重要原因;在妇女宫颈癌前病变过程中,CMV与HR-HPV协同感染与宫颈癌前病变的发展相关,常规HPV和CMV-DNA检测在宫颈癌筛查中有重要价值.%Objective To investigate infection rate of human papillomavirus as well as the correlation between cervical precancerous lesions and co-infection of human HPV,herpes simple virus-2 (HSV-2) and cytomegalovirus (CMV) in Chinese women of

  18. 巨细胞病毒感染与儿童免疫性血小板减少性紫癜的关系探讨%Exploration of the relationship between human cytomegalovirus infection and immune thrombocytopenic purpura in children

    Institute of Scientific and Technical Information of China (English)

    颜慕霞; 张力; 林涛

    2011-01-01

    Objective To explore the relationship between human cytomegalovirus (HCMV) infection and immune thrombocytopenic purpura (ITP) in children. Methods HCMV DNA in serum samples from 154 cases with ITP(ITP groups)and 50 healthy children (control groups) was detected by Real-time PCR. HCMV IgM and HCMV IgC were tested by ELISA simultaneously. Urine specimens from 105 cases in ITP group and 50 children in control group were collected for the detection of HCMV DNA by Real-time PCR. At the same time, amount of platelet (PLT) in HCMV DNA positive children was compared with that of the HCMV DNA negative ones for the ITP groups. Results The positive rates of HCMV DNA, HCMV IgM and HCMV IgG in serum samples in the ITP group were higher than those in the control group, and the HCMV DNA in urine specimens was also found in more cases in the ITP group. There was significant difference between both groups (P<0.01). There were significant difference of PLT between HCMV DNA positive children and the negative ones in the ITP group (P<0.05).Conclusion HCMV infection may be an important pathogenic factor in ITP. This finding is important for the treatment and prevention of ITP.%目的 探讨人巨细胞病毒(HCMV)感染与儿童免疫性血小板减少性紫癜(ITP)的关系.方法 采集154例ITP患儿(ITP组)和50例健康儿童(对照组)的血清样本,用Real-time PCR检测HCMV DNA,ELISA方法检测HCMV IgM、IgG抗体;其中105例ITP患儿和50例健康对照儿童采集了尿液标本,用Real-time PCR检测HCMV DNA.并比较ITP组HCMV DNA阳性患儿与阴性患儿的血小板数量的差异.结果 ITP患儿血清HCMV DNA、HCMV IgM及IgG抗体和尿HCMV DNA阳性率均明显高于健康对照儿童,两组比较差异均有统计学意义(P<0.01);ITP组HCMV DNA阳性患儿的血小板数量(29.72±14.54)x10~9/L与阴性患儿(41.28±18.35)x10~9/L比较差异有统计学意义(P<0.05).结论 儿童感染HCMV可能是发生ITP的重要致病因素之一,这对指导临床有

  19. Washing our hands of the congenital cytomegalovirus disease epidemic

    Directory of Open Access Journals (Sweden)

    Cannon Michael J

    2005-06-01

    Full Text Available Abstract Background Each year in the United States, an estimated 40,000 children are born with congenital cytomegalovirus (CMV infection, causing an estimated 400 deaths and leaving approximately 8000 children with permanent disabilities such as hearing or vision loss, or mental retardation. More children are affected by serious CMV-related disabilities than by several better-known childhood maladies, including Down syndrome, fetal alcohol syndrome, and spina bifida. Discussion Congenital CMV is a prime target for prevention not only because of its substantial disease burden but also because the biology and epidemiology of CMV suggest that there are ways to reduce viral transmission. Because exposure to the saliva or urine of young children is a major cause of CMV infection among pregnant women, it is likely that good personal hygiene, especially hand-washing, can reduce the risk of CMV acquisition. Experts agree that such measures are likely to be efficacious (i.e., they will work if consistently followed and the American College of Obstetricians and Gynecologists recommends that physicians counsel pregnant women about preventing CMV acquisition through careful attention to hygiene. However, because of concerns about effectiveness (i.e., Will women consistently follow hygienic practices as the result of interventions?, the medical and public health communities appear reluctant to embrace primary CMV prevention via improved hygienic practices, and educational interventions are rare. Current data on the effectiveness of such measures in preventing CMV infection are promising, but limited. There is strong evidence, however, that educational interventions can prevent other infectious diseases with similar transmission modes, suggesting that effective interventions can also be found for CMV. Until a CMV vaccine becomes available, effective educational interventions are needed to inform women about congenital CMV prevention. Summary Perhaps no single

  20. Absence of cross-presenting cells in the salivary gland and viral immune evasion confine cytomegalovirus immune control to effector CD4 T cells.

    Directory of Open Access Journals (Sweden)

    Senta M Walton

    2011-08-01

    Full Text Available Horizontal transmission of cytomegaloviruses (CMV occurs via prolonged excretion from mucosal surfaces. We used murine CMV (MCMV infection to investigate the mechanisms of immune control in secretory organs. CD4 T cells were crucial to cease MCMV replication in the salivary gland (SG via direct secretion of IFNγ that initiated antiviral signaling on non-hematopoietic cells. In contrast, CD4 T cell helper functions for CD8 T cells or B cells were dispensable. Despite SG-resident MCMV-specific CD8 T cells being able to produce IFNγ, the absence of MHC class I molecules on infected acinar glandular epithelial cells due to viral immune evasion, and the paucity of cross-presenting antigen presenting cells (APCs prevented their local activation. Thus, local activation of MCMV-specific T cells is confined to the CD4 subset due to exclusive presentation of MCMV-derived antigens by MHC class II molecules on bystander APCs, resulting in IFNγ secretion interfering with viral replication in cells of non-hematopoietic origin.

  1. Roles of phosphatidylinositol 3-kinase and NF-kappaB in human cytomegalovirus-mediated monocyte diapedesis and adhesion: strategy for viral persistence.

    Science.gov (United States)

    Smith, M Shane; Bivins-Smith, Elizabeth R; Tilley, A Michael; Bentz, Gretchen L; Chan, Gary; Minard, Jessica; Yurochko, Andrew D

    2007-07-01

    Infected peripheral blood monocytes are proposed to play a key role in the hematogenous dissemination of human cytomegalovirus (HCMV) to tissues, a critical step in the establishment of HCMV persistence and the development of HCMV-associated diseases. We recently provided evidence for a unique strategy involved in viral dissemination: HCMV infection of primary human monocytes promotes their transendothelial migration and differentiation into proinflammatory macrophages permissive for the replication of the original input virus. To decipher the mechanism of hematogenous spread, we focused on the viral dysregulation of early cellular processes involved in transendothelial migration. Here, we present evidence that both phosphatidylinositol 3-kinase [PI(3)K] and NF-kappaB activities were crucial for the HCMV induction of monocyte motility and firm adhesion to endothelial cells. We found that the beta(1) integrins, the beta(2) integrins, intracellular adhesion molecule 1 (ICAM-1), and ICAM-3 were upregulated following HCMV infection and that they played a key role in the firm adhesion of infected monocytes to the endothelium. The viral regulation of adhesion molecule expression is complex, with PI(3)K and NF-kappaB affecting the expression of each adhesion molecule at different stages of the expression cascade. Our data demonstrate key roles for PI(3)K and NF-kappaB signaling in the HCMV-induced cellular changes in monocytes and identify the biological rationale for the activation of these pathways in infected monocytes, which together suggest a mechanism for how HCMV promotes viral spread to and persistence within host organs.

  2. Low Prevalence of Varicella Zoster Virus and Herpes Simplex Virus Type 2 in Saliva from Human Immunodeficiency Virus-Infected Persons in the Era of Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Wang, Chunmei C.; Yepes, Luis C.; Danaher, Robert J.; Berger, Joseph R.; Mootoor, Yunanan; Kryscio, Richard J.; Miller, Craig S.

    2009-01-01

    Objectives Human herpesviruses (HHVs), e.g. herpes simplex virus (HSV) type 1, Epstein-Barr virus and cytomegalovirus, appear in saliva at greater frequency in persons infected with human immunodeficiency virus (HIV) than healthy individuals. However, it is not known if varicella zoster virus (VZV) and HSV-2 appear simultaneously during HIV infection at greater frequency in saliva during this era of highly active antiretroviral therapy (HAART). The aim of this study was to investigate the prevalence and amounts of VZV and HSV-2 in the saliva of HIV-infected, orally asymptomatic patients. Study Design Quantitative polymerase chain reaction was used to investigate the prevalence, quantity, risk, and correlates of salivary VZV and HSV-2 from 59 HIV-seropositive individuals and 53 healthy controls in a case-control, cross-sectional study. Seventy-eight percent of the HIV-seropositive patients (46/59) were taking HAART. Results VZV DNA was detected in the saliva of 5.1% (3/59) of the HIV-positive group and in only one healthy control 1.9% (1/53; P = 0.62). The amount of VZV DNA in the expressors was low, generally less than 1,100 copies/mL with no observed difference between the HIV-positive group and the controls (P= 1.0). HSV-2 DNA was not detected in either group. In the HIV-infected group, VZV shedding occurred in those on HAART, but was not associated with oral lesions, specific CD4+ or CD8+ T-cell levels, or demographic factors. Conclusions VZV was detected at low prevalence in the saliva of HIV-infected persons whereas HSV-2 was not detected in the saliva of this cohort. HAART does not appear to diminish the risk for asymptomatic VZV shedding. PMID:20123407

  3. The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding

    Energy Technology Data Exchange (ETDEWEB)

    Nemčovičová, Ivana [La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037 (United States); Slovak Academy of Sciences, Dúbravská cesta 9, SK 84505 Bratislava (Slovakia); Zajonc, Dirk M., E-mail: dzajonc@liai.org [La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037 (United States)

    2014-03-01

    The crystal structure of Human cytomegalovirus immune modulator UL141 was solved at 3.25 Å resolution. Here, a detailed analysis of its intimate dimerization interface and the biophysical properties of its receptor (TRAIL-R2 and CD155) binding interactions are presented. Natural killer (NK) cells are critical components of the innate immune system as they rapidly detect and destroy infected cells. To avoid immune recognition and to allow long-term persistence in the host, Human cytomegalovirus (HCMV) has evolved a number of genes to evade or inhibit immune effector pathways. In particular, UL141 can inhibit cell-surface expression of both the NK cell-activating ligand CD155 as well as the TRAIL death receptors (TRAIL-R1 and TRAIL-R2). The crystal structure of unliganded HCMV UL141 refined to 3.25 Å resolution allowed analysis of its head-to-tail dimerization interface. A ‘dimerization-deficient’ mutant of UL141 (ddUL141) was further designed, which retained the ability to bind to TRAIL-R2 or CD155 while losing the ability to cross-link two receptor monomers. Structural comparison of unliganded UL141 with UL141 bound to TRAIL-R2 further identified a mobile loop that makes intimate contacts with TRAIL-R2 upon receptor engagement. Superposition of the Ig-like domain of UL141 on the CD155 ligand T-cell immunoreceptor with Ig and ITIM domains (TIGIT) revealed that UL141 can potentially engage CD155 similar to TIGIT by using the C′C′′ and GF loops. Further mutations in the TIGIT binding site of CD155 (Q63R and F128R) abrogated UL141 binding, suggesting that the Ig-like domain of UL141 is a viral mimic of TIGIT, as it targets the same binding site on CD155 using similar ‘lock-and-key’ interactions. Sequence alignment of the UL141 gene and its orthologues also showed conservation in this highly hydrophobic (L/A)X{sub 6}G ‘lock’ motif for CD155 binding as well as conservation of the TRAIL-R2 binding patches, suggesting that these host

  4. Cytomegalovirus enterocolitis in a patient with diffuse large B-cell lymphoma after chemotherapy with rituximab

    Institute of Scientific and Technical Information of China (English)

    Jason Seewoodhary

    2006-01-01

    Rituximab has been associated with the development of cytomegalovirus enterocolitis in immunosuppressed patients. A 51-year-old patient with diffuse large B-cell lymphoma who received a conditioning chemotherapy regimen (RCVP and RICE) consisting of rituximab before bone marrow transplantation went on to develop cytomegalovirus enterocolitis. This supports evidence from previously described cases that rituximab may be associated with cytomegalovirus enterocolitis.

  5. 76 FR 69743 - The Development and Evaluation of Human Cytomegalovirus Vaccines; Public Workshop

    Science.gov (United States)

    2011-11-09

    ... HUMAN SERVICES Food and Drug Administration The Development and Evaluation of Human Cytomegalovirus... Development and Evaluation of Human Cytomegalovirus Vaccines.'' The purpose of the public workshop is to identify and discuss key issues related to the development and evaluation of human cytomegalovirus...

  6. Antileishmanial activity of licochalcone A in mice infected with Leishmania major and in hamsters infected with Leishmania donovani

    DEFF Research Database (Denmark)

    Chen, M; Christensen, S B; Theander, T G;

    1994-01-01

    This study was designed to examine the antileishmanial activity of the oxygenated chalcone licochalcone A in mice and hamsters infected with Leishmania parasites. Intraperitoneal administration of licochalcone A at doses of 2.5 and 5 mg/kg of body weight per day completely prevented lesion...... development in BALB/c mice infected with Leishmania major. Treatment of hamsters infected with L. donovani with intraperitoneal administration of licochalcone A at a dose of 20 mg/kg of body weight per day for 6 consecutive days resulted in a > 96% reduction of parasite load in the liver and the spleen...

  7. Severe gastrointestinal cytomegalovirus disease in two patients with renal vasculitis after immunosuppression.

    Science.gov (United States)

    Lee, Kian-Guan; Teo, Su-Hooi; Lim, Cynthia; Loh, Alwin; Chidambaram, Viswanath; Choo, Jason

    2016-09-01

    Although the use of current immunosuppressive regimens has significantly improved the outcomes of autoimmune renal diseases, infectious complications remain an important clinical concern. Cytomegalovirus (CMV) infection has been shown to be one of the major causes of mortality in this group of patients. We report two cases of renal vasculitis (Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)) that developed into severe gastrointestinal CMV disease and manifested with massive small bowel bleeding, resulting in an eventual fatal outcome for one of the patients. Risk factors, pathogenesis, role of immunosuppression in the development of CMV infection, and antiviral treatment are discussed in this review. These cases highlight the need for further research to evaluate the complex mechanisms between immunosuppression and CMV occurrence as well as the role of antiviral prophylaxis in high-risk patients undergoing immunosuppressive therapies.
. PMID:27443566

  8. SEQUENCE CONSERVATION OF HUMAN CYTOMEGALOVIRUS UL140 OPEN READING FRAME IN CLINICAL STRAINS

    Institute of Scientific and Technical Information of China (English)

    Ying Qi; Yan-ping Ma; Rong He; Zheng-rong Sun; Yaohua Ji; Yu-jing Huang; Qiang Ruan

    2008-01-01

    Objective To investigate the variability of human cytomegalovirus (HCMV) UL140 open reading frame (ORF)in clinical strains, and to explore the relationship between the variability of UL140 ORF and different symptoms of HC-MV infection.Methods HCMV ULI40 ORF was amplified by polymerase chain reaction and sequenced selectedly in 30 clinical strains.Results UL140 ORF of all clinical strains was amplified successfully. Compared with that of Toledo strain, the nncleotide and amino acid sequence identifies among all strains were 96.5% -100.0% and 95.2% -100.0%, respective-ly. All of the nucleotide changes were substitutions. The post-translational modification sites were conserved. The result of phylogenetic tree showed that the strains did not cluster according to different clinical symptoms.Conclusion HCMV UL140 ORF in clinical strains is highly conserved, which may play an important role in HC-MV infection.

  9. 亲属单倍型与同胞全相合HSCT后巨细胞病毒感染临床特点的比较%Comparative study on clinical features of cytomegalovirus infection after allogenic hematopoietic stem cell transplantation from HLA haploidentical related donors vs HLA-matched sibling donors

    Institute of Scientific and Technical Information of China (English)

    黄金菊; 陆晓茜; 闫晨华; 赵晓甦; 许兰平; 黄晓军; 刘代红

    2013-01-01

    Objective To compare the clinical features of cytomegalovirus (CMV) infection and CMV disease after allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA haploidentical related doors vs.HLA-matched sibling donors.Methods A total of 327 patients who received allogeneic HSCT from Jan.2011 to Dec.2011 were enrolled.There were 312 patients who had complete serological data before HSCT including 216 cases of HLA haploidentical related HSCT and 96 cases of HLA-matched sibling HSCT.Monitoring of CMV antigenemia was performed by using real-time quantitative (RQ) PCR after transplantation.Risk factors were compared by univariate and multivariate analysis.Results The cumulative incidence of CMV infection and CMV disease was (80.1 ± 2.7) % and (8.7 ± 2.0) % in HLA haploiddentical HSCT group,and (21.1 ± 4.9) % and 0 in HLA-matched sibling HSCT group respectively,and the difference was statistically significant between the two groups (P<0.01).Univariate analysis revealed that HLA haploidentical related HSCT,less than 20 years of age,high risk disease,CMV-IgG serum positivity in patients or donors,acute graft-versus-host disease (aGVHD),EB viremia,and hemorrhagic cystitis were the risk factors of CMV infection.HLA haploidentical related SCT and hemorrhagic cystitis were the risk factors for CMV disease.Multivariate analysis showed that patients less than 20 years of age had a significantly high incidence of CMV infection.Patients from HLA-matched sibling HSCT,low risk disease,aGVHD,hemorrhagic cystitis had a significantly low incidence of CMV infection.Conclusion Compared with patients receiving HLA-matched sibling HSCT,those who received HLA haploidentical related HSCT had significantly high incidence of CMV infection and CMV disease,which were correlated with incidence of hemorrhagic cystitis.%目的 比较亲属单倍型与同胞全相合异基因造血干细胞移植(HSCT)受者巨细胞病毒(CMV)感染及CMV病的临床特点.方法 2011年1-12

  10. Reversible silencing of cytomegalovirus genomes by type I interferon governs virus latency.

    Directory of Open Access Journals (Sweden)

    Franziska Dağ

    2014-02-01

    Full Text Available Herpesviruses establish a lifelong latent infection posing the risk for virus reactivation and disease. In cytomegalovirus infection, expression of the major immediate early (IE genes is a critical checkpoint, driving the lytic replication cycle upon primary infection or reactivation from latency. While it is known that type I interferon (IFN limits lytic CMV replication, its role in latency and reactivation has not been explored. In the model of mouse CMV infection, we show here that IFNβ blocks mouse CMV replication at the level of IE transcription in IFN-responding endothelial cells and fibroblasts. The IFN-mediated inhibition of IE genes was entirely reversible, arguing that the IFN-effect may be consistent with viral latency. Importantly, the response to IFNβ is stochastic, and MCMV IE transcription and replication were repressed only in IFN-responsive cells, while the IFN-unresponsive cells remained permissive for lytic MCMV infection. IFN blocked the viral lytic replication cycle by upregulating the nuclear domain 10 (ND10 components, PML, Sp100 and Daxx, and their knockdown by shRNA rescued viral replication in the presence of IFNβ. Finally, IFNβ prevented MCMV reactivation from endothelial cells derived from latently infected mice, validating our results in a biologically relevant setting. Therefore, our data do not only define for the first time the molecular mechanism of IFN-mediated control of CMV infection, but also indicate that the reversible inhibition of the virus lytic cycle by IFNβ is consistent with the establishment of CMV latency.

  11. Implementing neonatal screening for congenital cytomegalovirus: addressing the deafness of policy makers.

    Science.gov (United States)

    de Vries, Jutte J C; Vossen, Ann C T M; Kroes, Aloys C M; van der Zeijst, Bernard A M

    2011-01-01

    Congenital cytomegalovirus (CMV) infection is an important public health problem with approximately 7 in 1,000 newborns infected and consequently at risk for hearing impairment. Newborn hearing screening will fail to detect this hearing impairment in approximately half of the cases because late onset hearing loss is frequent. Hearing impairment has profound impact on cognitive and social development of children and their families, determining most of the disease burden of congenital CMV infection. The potential value of newborn screening for congenital CMV is increasingly discussed. To date, many experts acknowledge the benefit of antiviral treatment in the prevention of hearing deterioration in newborns with neurological symptoms, and the benefit of early identification of late-onset hearing impairment by means of extensive audiological follow up of infected infants. These opinions imply that the potential of newborn screening for CMV would lie in the identification of the large proportion of asymptomatic congenitally infected newborns at risk for developing late-onset hearing loss. Experience with postnatal antiviral treatment of symptomatic newborns is encouraging, but has not been studied in asymptomatic congenitally infected newborns. A large-scale study on the safety and effectiveness of combined screening and antiviral therapy for congenital CMV infection is the necessary next step to take and should not be delayed.

  12. Association between cytomegalovirus antibody levels and cognitive functioning in non-elderly adults.

    Directory of Open Access Journals (Sweden)

    Faith Dickerson

    Full Text Available BACKGROUND: Elevated levels of antibodies to Cytomegalovirus (CMV have been associated with cognitive impairment, but the quantitative relationship between CMV antibody levels and domains of cognitive functioning in younger adults has not been established. METHODS: We measured IgG class antibodies to Cytomegalovirus in 521 individuals, mean age 32.8 years. Participants were selected for the absence of psychiatric disorder and of a serious medical condition that could affect brain functioning. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, the Wisconsin Card Sorting Test, Trail Making Test part A, and the WAIS III Letter Number Sequencing subtest. Linear regression analyses were used to measure the quantitative association between cognitive scores and Cytomegalovirus IgG antibody level. Logistic regression analyses were used to measure the odds of low cognitive scores and elevated antibody levels defined as an antibody level > = 50th, 75th, and 90th percentile of the group. RESULTS: Higher levels of CMV antibodies were associated with lower performance on RBANS Total (coefficient -1.03, p<.0002, Delayed Memory (coefficient -0.94, p<.001, Visuospatial/Constructional (coefficient -1.77, p<5×10(-7, and Letter Number Sequencing (coefficient -0.15, p<.03. There was an incremental relationship between the level of CMV antibody elevation and the odds of a low RBANS Total score. The odds of a low total cognitive score were 1.63 (95th % CI 1.01, 2.64; p<.045, 2.22 (95th % CI 1.33, 3.70; p<.002, and 2.46 (95th % CI 1.24, 4.86; p<.010 with a CMV antibody level greater than or equal to the 50th, 75th, and 90th percentile respectively. CONCLUSIONS: Higher levels of Cytomegalovirus antibodies are associated with lower levels of cognitive functioning in non-elderly adults. Methods for the prevention and treatment of CMV infection should be evaluated to determine if they result in an

  13. Association between Cytomegalovirus Antibody Levels and Cognitive Functioning in Non-Elderly Adults

    Science.gov (United States)

    Dickerson, Faith; Stallings, Cassie; Origoni, Andrea; Katsafanas, Emily; Schweinfurth, Lucy A. B.; Savage, Christina L. G.; Yolken, Robert

    2014-01-01

    Background Elevated levels of antibodies to Cytomegalovirus (CMV) have been associated with cognitive impairment, but the quantitative relationship between CMV antibody levels and domains of cognitive functioning in younger adults has not been established. Methods We measured IgG class antibodies to Cytomegalovirus in 521 individuals, mean age 32.8 years. Participants were selected for the absence of psychiatric disorder and of a serious medical condition that could affect brain functioning. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Wisconsin Card Sorting Test, Trail Making Test part A, and the WAIS III Letter Number Sequencing subtest. Linear regression analyses were used to measure the quantitative association between cognitive scores and Cytomegalovirus IgG antibody level. Logistic regression analyses were used to measure the odds of low cognitive scores and elevated antibody levels defined as an antibody level > = 50th, 75th, and 90th percentile of the group. Results Higher levels of CMV antibodies were associated with lower performance on RBANS Total (coefficient −1.03, p<.0002), Delayed Memory (coefficient −0.94, p<.001), Visuospatial/Constructional (coefficient −1.77, p<5×10−7), and Letter Number Sequencing (coefficient −0.15, p<.03). There was an incremental relationship between the level of CMV antibody elevation and the odds of a low RBANS Total score. The odds of a low total cognitive score were 1.63 (95th % CI 1.01, 2.64; p<.045), 2.22 (95th % CI 1.33, 3.70; p<.002), and 2.46 (95th % CI 1.24, 4.86; p<.010) with a CMV antibody level greater than or equal to the 50th, 75th, and 90th percentile respectively. Conclusions Higher levels of Cytomegalovirus antibodies are associated with lower levels of cognitive functioning in non-elderly adults. Methods for the prevention and treatment of CMV infection should be evaluated to determine if they result in an

  14. Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Andersen, Ove; Eugen-Olsen, Jesper; Kofoed, Kristian;

    2008-01-01

    Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected...

  15. 系统性红斑狼疮患者并发 EB 病毒或巨细胞病毒感染的回顾性分析%Retrospective Analysis of Epstein Barr Virus or Cytomegalovirus Infection in Patients with Systemic Lupus Erythematosus

    Institute of Scientific and Technical Information of China (English)

    宋宏岩; 王红; 李雷; 魏红霞; 陈军浩; 王庆飞

    2016-01-01

    目的:探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)患者并发 EB 病毒(epstein barr virus,EBV)或巨细胞病毒(cytomegalovirus,CMV)感染的流行病学特征,为临床提供参考。方法回顾性分析2012年1月~2015年4月在南京大学医学院附属鼓楼医院就诊入院的202例女性 SLE 患者(SLE 组)的相关临床资料,以同期的女性肾移植供者和妇产科送检标本共203例作为对照组;根据实时荧光定量 PCR 检测外周血中 EB 病毒 DNA 和巨细胞病毒 DNA 结果,分析、比较 SLE 组和对照组的感染发生率。结果 SLE 患者中 EBV-DNA 的阳性率(11.39%)显著高于对照组的阳性率(3.45%),差异具有统计学意义(χ2=8.28,P <0.01);SLE 组 CMV-DNA 的阳性率(7.92%)显著高于对照组的阳性率(1.97%),差异具有统计学意义(χ2=7.64,P <0.05)。128例育龄期 SLE 患者 EBV-DNA 的阳性率(10.94%)显著高于对照组的阳性率(3.45%),差异具有统计学意义(χ2=4.99,P <0.05);育龄期 SLE 组 CMV-DNA 的阳性率(7.75%)显著高于对照组的阳性率(2.22%),差异具有统计学意义(χ2=4.31,P <0.05)。结论SLE 患者易并发 EB 病毒或巨细胞病毒感染,提示 SLE 与病毒感染可能具有相关性,在临床工作中应加以重视。%Objective To analyze the epidemiological characteristics of Epstein Barr virus (EBV)or cytomegalovirus (CMV) infection in systemic lupus erythematosus (SLE)patients in order to provide reference for clinic.Methods The clinical data of 202 female cases in-patients diagnosed with SLE (SLE group)from January 2012 to May 2015 in Nanjing Drum Tower Hospital were analyzed retrospectively.Meanwhile,203 cases including female renal transplant donors,obstetrics and gyne-cology in-patients selected randomly were enrolled as control group.The infection rate between SLE and control groups was

  16. A Modified Peptide Stimulation Method for Efficient Amplification of Cytomegalovirus (CMV)-Specific CTLs

    Institute of Scientific and Technical Information of China (English)

    Guangping Ruan; Li Ma; Qian Wen; Wei Luo; Mingqian Zhou; Xiaoning Wang

    2008-01-01

    CMV-specific immunity is essential for control of human cytomegalovirus (HCMV) infection. Stem cell trans- plantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of CMV-specific CD8+ T cell clones has been shown to reduce the rate of viral reactivation; however, the ex vivo production of cells for adoptive transfer is labor intensive and exp