WorldWideScience

Sample records for active cytomegalovirus infections

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

    Directory of Open Access Journals (Sweden)

    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. Activity of histidine in peripheral blood erythrocytes of pregnant women during exacerbation of cytomegalovirus infection.

    Science.gov (United States)

    Lutsenko, M T; Andrievskaya, I A

    2014-10-01

    We studied the effect of active cytomegalovirus infection on histidine content in peripheral blood erythrocytes of pregnant women at gestation weeks 20-22 and its involvement into hemoglobin oxygenation. Using the histochemical technique developed by us, we studied the distribution of products of specific reaction for histidine in peripheral blood erythrocytes of pregnant women. The percentage of histidine-positive erythrocytes and their area were evaluated. The relationship between the distribution of the products of the reaction for histidine in peripheral blood erythrocytes of pregnant women and the titer of anti-cytomegalovirus IgG was revealed. The histidine content in peripheral blood erythrocytes of pregnant women with active cytomegalovirus infection was reduced, which impaired heme binding to globin and decreased the formation of oxyhemoglobin.

  3. Cytomegalovirus infection in transplant recipients

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Scott W Cousins

    Full Text Available The neovascular (wet form of age-related macular degeneration (AMD leads to vision loss due to choroidal neovascularization (CNV. Since macrophages are important in CNV development, and cytomegalovirus (CMV-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV, laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF, an outcome that requires active virus replication.

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

    Directory of Open Access Journals (Sweden)

    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

  7. Congenital and perinatal cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    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.

  8. The advent of Cytomegalovirus infection in HIV infected patients: A review

    Directory of Open Access Journals (Sweden)

    Sundar Isaac Kirubakaran

    2004-03-01

    Full Text Available Cytomegalovirus is considered as one among the long list of latent infections in humans that although normally controlled by the cellular immune response, gets activated after HIV infection takes its role on infecting the T4 lymphocytes. Clinical disease due to Cytomegalovirus has been recognized in up to 40% of patients with advanced HIV disease. The clinical syndromes most commonly associated include chorioretinitis, esophagitis, colitis, pneumonitis, adrenalitis and neurological disorders. Cytomegalovirus infections are usually diagnosed clinically and by serological tests for CMV immunoglobulin. Chemotherapy using systemic agents, including ganciclovir, intravenous foscarnet and intravenous cidofovir is effective. New agents, as for example an anti-sense agent against cytomegalovirus, appear promising.

  9. Cytomegalovirus Infection and Pre-Eclampsia

    OpenAIRE

    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.

  10. Cytomegalovirus Infection and Pre-Eclampsia

    Directory of Open Access Journals (Sweden)

    Rădulescu Carmen

    2016-06-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  12. Human Cytomegalovirus Manipulation of Latently Infected Cells

    Directory of Open Access Journals (Sweden)

    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.

  13. [Cycloferon therapy of cytomegalovirus infection in monkeys].

    Science.gov (United States)

    Mezentseva, M V; Agrba, V Z; Karal-ogly, D D; Agumava, A A

    2012-01-01

    Cytomegalovirus (CMV) infection is a wide-spread disease throw humans and monkeys, which and associated with various diseases. The development of this infection in human organism is much like that in rhesus macaque, which makes CMV-infected monkeys adequate model for studying and elaborating prophylactic and therapeutic measures against this disease in humans. This article presents data on the efficiency of cycloferon action on animals with the M. mulatta CMV infection. Cycloferon stimulated an increase in the IFN-alpha production and promoted the period of remission in CMV-infected animals.

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

    Science.gov (United States)

    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.

  15. Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection

    Science.gov (United States)

    Alsaeed, Mohammed; Ballool, Sulafa; Attia, Ashraf

    2016-01-01

    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. PMID:27703835

  16. Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    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.

  17. [Ulcerative colitis and cytomegalovirus infection].

    Science.gov (United States)

    Tárraga Rodríguez, I; Ferreras Fernández, P; Vicente Gutiérrez, M; de Arriba, J J; García Mouriño, M L

    2003-02-01

    Colitis ulcerous and citomegalovirus infection association have been reported in medical literature in sometimes, althougth this prevalence have lately increased. We report a case record of this association and do a review of this subject. It is not clear what factors are involved in this association, being necessary hore studies to know them.

  18. 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...

  19. Congenital cytomegalovirus infection in San Luis Potosi, Mexico.

    Science.gov (United States)

    Noyola, Daniel E; Mejía-Elizondo, Ana R; Canseco-Lima, Jesús M; Allende-Carrera, Ricardo; Hernánsez-Salinas, Alba E; Ramírez-Zacarías, José L

    2003-01-01

    The incidence of congenital cytomegalovirus infection in Mexico is unknown. We evaluated the presence of cytomegalovirus infection in 560 newborn infants at a public general hospital. There were five (0.89%) infected newborns. Infants with congenital infection were more likely to be born to primigravid mothers (P = 0.01) and were more often from rural areas (P = 0.058) than were noninfected newborns.

  20. [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.

  1. 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

  2. [{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.

  3. Prognostic markers of symptomatic congenital cytomegalovirus infection.

    Science.gov (United States)

    Romanelli, Roberta Maia de Castro; Magny, Jean François; Jacquemard, François

    2008-02-01

    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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Evolution of hearing in children with congenital cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Ibáñez-Muñoz C, Calle-Cabanillas M.I, Pérez-Sáez J, Navazo-Eguía A.I, Clemente-García A, García-Vicario F, Sánchez-Hernández JM

    2013-10-01

    Full Text Available Introduction and Objectives: Congenital cytomegalovirus infection (CMV is the most common congenital viral infection and the most common cause of acquired congenital sensorineural hearing loss. Objective: To evaluate the characteristics and evolution of hearing in patients diagnosed with congenital cytomegalovirus (CMV infection. Methods and materials: In a retrospective study assessed the characteristics and evolution of hearing in children born in our hospital between 2000 and 2010 with symptomatic congenital cytomegalovirus infection. Depending on the age and neurological status, hearing assesment was performed by objective audiometry, audiometry through play or conventional audiometry. Results: During the period of 2000-2010 have been identified 5 cases of symptomatic congenital cytomegalovirus (0.025% of newborns, predominantly female (60%. In 40% of cases was the only symptom suspected microcephaly. In both instances the hearing was normal at birth, presenting one of the cases of late-onset profoundly deaf. One case (20% had major neurological involvement with petechiae, hepatosplenomegaly and profound sensorineural hearing loss. Two cases were very premature with other risk factors but no hearing impairment. All cases were treated with ganciclovir. Conclusion: It is necessary to identify patients with congenital CMV infection and hearing track during the first years of life due to the possibility of developing late-onset hearing loss.

  11. 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 ...

  12. 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

  13. 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.

  14. 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,

  15. 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...

  16. Cytomegalovirus Infection in a Patient with Crohn’s Ileocolitis

    Directory of Open Access Journals (Sweden)

    Sahin Coban

    2005-01-01

    Full Text Available Cytomegaloviral enterocolitis is an uncommon infection that can complicate inflammatory bowel disease. A case of a patient with a three-year history of Crohn's disease is reported. He had been in a stable condition on mesalamine 4 g/day and methylprednisolone 10 mg/day for three years until four weeks before admission. The patient was admitted with complaints of fever, abdominal pain and watery diarrhea. A diagnosis of an exacerbation of Crohn's disease was established. The radiological examination revealed narrowing of the terminal ileum. Multiple fistulas and abscess-like images were observed. The patient then underwent ileocolic resection and ileostomy. The histopathological examination revealed Crohn's ileocolitis with superimposed cytomegalovirus infection. In patients with rapidly deteriorating inflammatory bowel disease, cytomegalovirus infection should be kept in mind as one of the differential diagnoses.

  17. Growth in agarose of human cells infected with cytomegalovirus.

    Science.gov (United States)

    Lang, D J; Montagnier, L; Latarjet, R

    1974-08-01

    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.

  18. Ruptura espontánea de bazo asociada a infección activa por citomegalovirus Spontaneous spleen rupture associated with active cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    P. J. Duarte

    2003-01-01

    Full Text Available Presentamos un paciente inmunocompetente de 24 años, sexo masculino, que padeció una ruptura espontánea de bazo (REB durante una infección activa (IA por citomegalovirus (CMV. El único antecedente clínico fue un cuadro gripal dos semanas antes de la REB. El diagnóstico de CMV fue confirmado por la presencia de anticuerpos IgM en suero y por PCR positiva para CMV en biopsia de pieza de esplenectomía. El paciente se recuperó completamente luego de la cirugía. La ruptura espontánea de bazo es un evento poco común en la IA por CMV y éste es el primer caso referido en nuestro país.We present a 24 year old immunocompetent male who developed a spontaneous rupture of the spleen (SRE during an acute cytomegalovirus (CMV infection. The only previous clinical feature was the presence of flu-like symptoms two weeks before the SRE. The diagnosis was confirmed by the presence of IgM antibodies to CMV in the serum and a positive CMV-PCR in the splenic biopsy after splenectomy. The patient recovered completely after surgery. Spontaneous splenic rupture is an uncommon event associated with primary cytomegalovirus infection, and this is the first case reported in our country.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. School failure and deafness after "silent" congenital cytomegalovirus infection.

    Science.gov (United States)

    Hanshaw, J B; Scheiner, A P; Moxley, A W; Gaev, L; Abel, V; Scheiner, B

    1976-08-26

    We found IgM antibody directed against cytomegalovirus in the umbilical-cord blood of 53 of 8644 newborns. Forty-four of the 53 had psychometric and pediatric evaluations at 3.5 to 7.0 years of age. The group's mean IQ was 102.5+/-22.4 (+/-S.D.), whereas in matched controls it was 111.7 (PC 0.025). Bilateral hearing loss was present in five of 40 children with antibody against cytomegalovirus and in one of 44 matched controls without antibody (P less than 0.1). Three of the antibody-positive children, however, had profound deafness, an abnormality that occurs once in approximately 1000 children. The predicted school failure rate, based on IQ, behavioral, neurologic and auditory test data, was 2.7 times that of matched socioeconomic controls and eight times that of randomly selected controls. We conclude that clinically inapparent congenital cytomegalovirus infection can adversely affect central-nervous-system development.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. Trends in the treatment of cytomegalovirus infection in oncohematological patients

    Directory of Open Access Journals (Sweden)

    D. N. Balashov

    2014-07-01

    Full Text Available Cytomegalovirus (CMV-related complications remain an extremely serious and urgent problem in immunocompromised patients. Ganciclovir (GCV is efficient for the treatment of CMV-infection, but myelotoxicity limits the possibilities of their application. In addition, prolonged or intermittent courses of antiviral drugs predispose to the development of CMV drug-resistant strains. Valganciclovir is a safe and effective alternative to intravenous GCV. Despite the well-spread application of effective methods of early detection and pre-emptive treatment, the issue of the control of CMV-infection is not resolved. High intensive immunoablative therapy (alemtuzumab, ATG, еtс. and hematopoietic stem cell transplantation (HSCT from alternative donors greatly increase the risk of life-threatening visceral CMV-infections in patients. Thereby, studies of new therapeutic approaches (for example, transfusion of CMV-specific T-cells are actually in process.

  9. 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.

  10. Trends in the treatment of cytomegalovirus infection in oncohematological patients

    Directory of Open Access Journals (Sweden)

    D. N. Balashov

    2013-01-01

    Full Text Available Cytomegalovirus (CMV-related complications remain an extremely serious and urgent problem in immunocompromised patients. Ganciclovir (GCV is efficient for the treatment of CMV-infection, but myelotoxicity limits the possibilities of their application. In addition, prolonged or intermittent courses of antiviral drugs predispose to the development of CMV drug-resistant strains. Valganciclovir is a safe and effective alternative to intravenous GCV. Despite the well-spread application of effective methods of early detection and pre-emptive treatment, the issue of the control of CMV-infection is not resolved. High intensive immunoablative therapy (alemtuzumab, ATG, еtс. and hematopoietic stem cell transplantation (HSCT from alternative donors greatly increase the risk of life-threatening visceral CMV-infections in patients. Thereby, studies of new therapeutic approaches (for example, transfusion of CMV-specific T-cells are actually in process.

  11. Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection

    Science.gov (United States)

    Tu, Wenjuan; Rao, Sudha

    2016-01-01

    The ability of the human immune system to protect against infectious disease declines with age and efficacy of vaccination reduces significantly in the elderly. Aging of the immune system, also termed as immunosenescence, involves many changes in human T cell immunity that is characterized by a loss in naïve T cell population and an increase in highly differentiated CD28- memory T cell subset. There is extensive data showing that latent persistent human cytomegalovirus (HCMV) infection is also associated with age-related immune dysfunction in the T cells, which might enhance immunosenescence. Understanding the molecular mechanisms underlying age-related and HCMV-related immunosenescence is critical for the development of effective age-targeted vaccines and immunotherapies. In this review, we will address the role of both aging and HCMV infection that contribute to the T cell senescence and discuss the potential molecular mechanisms in aged T cells. PMID:28082969

  12. Cutaneous Ulcer as Leading Symptom of Systemic Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Richard F. Guo

    2015-01-01

    Full Text Available Cytomegalovirus (CMV infection rarely manifests with skin ulcerations. We describe a case report of a 64-year-old woman with chronic immunosuppression for treatment of mixed connective tissue disease, presenting with new onset leg ulcerations after a recent change in immunosuppressive regimen. She subsequently developed fulminant hepatitis, encephalopathy, and pancytopenia and was found to have severe systemic CMV viremia. Skin ulcer biopsy was positive by immunohistochemical staining for CMV infected endothelial cells. Both systemic disease and skin ulcer rapidly improved after stopping immunosuppression and administering intravenous ganciclovir. New onset skin ulcers in an immunosuppressed individual, especially with recent changes in immunosuppressive regimen, should raise the suspicion of reactivation of CMV.

  13. Colonic perforation in a patient with systemic lupus erythematosus accompanied by cytomegalovirus infection: A case report

    OpenAIRE

    Yuichi Tachikawa; Hiroaki Nozawa; Junichiro Tanaka; Takeshi Nishikawa; Toshiaki Tanaka; Tomomichi Kiyomatsu; Keisuke Hata; Kazushige Kawai; Shinsuke Kazama; Hironori Yamaguchi; Soichiro Ishihara; Eiji Sunami; Joji Kitayama; Madoka Fujisawa; Katutoshi Takahashi

    2016-01-01

    Introduction: Cytomegalovirus (CMV) infection of the gastrointestinal tract is an uncommon illness, but can be observed in immunocompromised patients. Systemic lupus erythematosus (SLE) patients are generally at high risk of CMV infection. Here we report a subacute progressive case of colitis in SLE accompanied by cytomegalovirus infection. Presentation of case: The patient, a 79-year-old woman, was hospitalized complaining of fever, polyarthritis, and skin ulcer that had lasted seven days...

  14. 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.

  15. Evidence that neomycin inhibits human cytomegalovirus infection of fibroblasts.

    Science.gov (United States)

    Lobert, P E; Hober, D; Delannoy, A S; Wattré, P

    1996-01-01

    The effect of phosphoinositide-binding aminoglycosides, such as neomycin, gentamicin and streptomycin, on human cytomegalovirus (HCMV) infection of human fibroblasts MRC-5 was studied. The inhibition of HCMV infection was obtained with all of these molecules but neomycin was more effective than the others. We showed that the inoculation of the cells with cell-free viral suspension in presence of neomycin concentrations above 5 mM at 37 degrees C, inhibited more than 98% the HCMV infection. However, the preincubation of the fibroblasts with neomycin at 4 degrees C, before the removal of the drug and the inoculation of the cells, induced only a 30% decrease in the number of infected cells. Addition of neomycin after the HCMV-binding at 4 degrees C or the infection of the cells was less efficient to inhibit HCMV infection than the standard incubation of neomycin during inoculation of the fibroblasts. Indeed, 1 hour after the inoculation of the cells at 37 degrees C, neomycin still inhibited HCMV infection, but 4 hours after the inoculation, this drug had no effect on HCMV infection. Our findings demonstrated that neomycin must be present at the time of infection in order to exert a full inhibiting effect. The effect of neomycin on the HCMV infection was almost immediate upon the addition of the drug (binding and/or internalization) and after the virus internalization (inhibition of immediate-early events). We suggest that neomycin and other aminoglycoside antibiotics may interact with HCMV glycoproteins for binding to similar structural features of cell surface heparan sulfate proteoglycans and may inhibit HCMV infection in fibroblasts by disrupting phosphoinositide-mediated events in the cells.

  16. 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

  17. Infection by cytomegalovirus in patients with neonatal cholestasis Infecção por cytomegalovirus em pacientes com colestase neonatal

    Directory of Open Access Journals (Sweden)

    Nara Léia Gelle de OLIVEIRA

    2002-04-01

    Full Text Available Background - Neonatal cholestasis syndrome with an intra or extrahepatic origin has been associated to viral infections. The participation of the cytomegalovirus in the etiopathogenesis of neonatal hepatitis has been already known for some time, but only recently there have been indications that this virus may be one of the possible etiological factors for extrahepatic biliary atresia. Aims - To assess the prevalence of infection by cytomegalovirus in patients with intrahepatic cholestasis and extrahepatic cholestasis. To compare the clinical characteristics of the intrahepatic cholestasis and extrahepatic cholestasis groups with the cytomegalovirus serological results. Patients and Methods - This study consisted of 76 patients with neonatal cholestasis who were admitted between January 1980 and January 1999 when they underwent a cytomegalovirus serologic study using the ELISA method. A case note was kept on each patient with the following data: age of patient at admission, serologic result for cytomegalovirus, history of maternal infection, prematurity, fetal distress, birth weight, ponderal gain, choluria and fecal acholia. The final anatomic diagnosis of cholestasis was based on the results of an abdominal ultrasonography, a liver biopsy and its evolution. The patients were then divided into two groups: group I - intrahepatic cholestasis and group II - extrahepatic cholestasis. Each of these groups were then divided into two subgroups: subgroup A - positive serology (IgM for cytomegalovirus and subgroup B - negative serology (IgM for cytomegalovirus. Results - The frequency of positive serology (IgM for cytomegalovirus was 29.4% in children with intrahepatic cholestasis and 28.5% in children with extrahepatic cholestasis. In comparison with group IIB, group IIA presented a higher rate of maternal infection history. The patients in group IIA demonstrated a delayed access to the service in comparison with group IA. The groups did not

  18. Aquired Cytomegalovirus Infection of Extremely Low Birth Weight Infant

    Directory of Open Access Journals (Sweden)

    Serdar Alan

    2013-12-01

    Full Text Available Breast milk is a major source for acquired cytomegalovirus infection especially in premature infants and acquired CMV infection occurs in infants whose mothers were seropositive for CMV. Although most of mothers of premature infants are seropositive in Turkey, acquired life-threatening breast milk acquired CMV infection was reported occasionally. Treatment of preterm with symptomatic breast milk acquired CMV infection should be done according to the severity of clinical signs. In this report, a preterm case with a diagnosis of breast milk-acquired CMV meningitis and sepsis without multiorgan failure on the 111th day of life, who did not require antiviral therapy was presented and discussed in the context of the acquired CMV literature. In preterm babies, when there is sepsis with no apparent causes, unexplained thrombocytopenia, elevated liver transaminases and direct hyperbilirubinemia acquired CMV infection should be suspected. (Jo­ur­nal of Cur­rent Pe­di­at­rics 2013; 11: 138-41

  19. Evaluation of cytomegalovirus (CMV)-specific T-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients.

    Science.gov (United States)

    Clari, María A; Aguilar, Gerardo; Benet, Isabel; Belda, Javier; Giménez, Estela; Bravo, Dayana; Carbonell, José A; Henao, Liliana; Navarro, David

    2013-10-01

    The current study was designed to assess the predictive value of the evaluation of cytomegalovirus (CMV)-specific T-cell immunity early following admission to the intensive care unit for inferring the risk of active CMV infection in non-immunosuppressed surgical and trauma patients. A total of 31 CMV-seropositive patients were included. Patients were screened for the presence of CMV DNA in plasma and in tracheal aspirates by real-time PCR. Enumeration of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T cells was performed by flow cytometry for intracellular cytokine staining. Virological and immunological monitoring was conducted once or twice a week. Active CMV infection occurred in 17 out of 31 patients. Undetectable levels of pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell subsets cells were observed in 10 patients who developed active CMV infection and in one who did not (at a median of 2 days following ICU admission). Peak CMV DNA loads in both tracheal aspirates and plasma were substantially higher (P = 0.018 and P = 0.091, respectively) in patients with undetectable IFN-γ T-cell responses than in patients with detectable responses. The expansion of both CMV-specific T-cell subsets following detection of active CMV infection was demonstrated in 9 out of 14 patients with active CMV infection. In conclusion, the evaluation of CMV pp65 and IE-1-specific IFN-γ-producing CD8(+) and CD4(+) T cells early following ICU admission may allow the identification of patients most at risk of either having or developing an episode of active CMV infection, particularly those associated with high-level virus replication.

  20. Coexisting cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis.

    Science.gov (United States)

    Chan, Khee-Siang; Lee, Wen-Ying; Yu, Wen-Liang

    2016-12-01

    Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients with human immunodeficiency virus infection, organ transplantation, and malignancy receiving chemotherapy or ulcerative colitis receiving immunosuppressive agents. However, CMV colitis is increasingly recognized in immunocompetent hosts. Notably, CMV colitis coexisting with Clostridium difficile infection (CDI) in apparently healthy individuals has been published in recent years, which could result in high morbidity and mortality. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with abdominal pain, watery, or especially bloody diarrhea, which could be refractory to standard treatment for CDI. As a characteristic of CDI, however, pseudomembranous colitis may be only caused by CMV infection. Real-time CMV-polymerase chain reaction (PCR) for blood and stool samples may be a useful and noninvasive diagnostic strategy to identify CMV infection when treatment of CDI eventually fails to show significant benefits. Quantitative CMV-PCR in mucosal biopsies may increase the diagnostic yield of traditional histopathology. CMV colitis is potentially life-threatening if severe complications occur, such as sepsis secondary to colitis, massive colorectal bleeding, toxic megacolon, and colonic perforation, so that may necessitate pre-emptive antiviral treatment for those who are positive for CMV-PCR in blood and/or stool samples while pending histological diagnosis.

  1. 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.

  2. Human Leukocyte Antigen Alleles and Cytomegalovirus Infection After Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Futohi

    2015-11-01

    Full Text Available Background Several studies have been conducted on the relationship between a number of human leukocyte antigen (HLA alleles and cytomegalovirus infection (CMV, in kidney transplant recipients, after transplantation. However, only a limited number of HLAs have been investigated, so far, and the results have been contradictory. Objectives This study aimed to investigate the relationship between 59 HLA alleles and the CMV infection, in transplant recipients, after kidney transplantation. Patients and Methods This retrospective cohort study was conducted on 200 patients, receiving a kidney transplant, in Baqiyatallah Hospital, in Tehran, during 2013. Throughout a one-year follow-up of kidney transplant recipients, in case of detecting the CMV antigen in patients’ blood, at any time, they were placed in the group of patients with CMV infection, whereas, if no CMV-specific antigen was developed, over a year, patients were placed in the group of patients without CMV infection, after transplantation. This study investigated the relationship between CMV infection in kidney transplant recipients and 59 HLA alleles, including 14 HLA-A, 28 HLA-B, and 17 HLA-DRB1 cases. Results Of all participants, 104 patients (52% were diagnosed with CMV infection. There was no significant difference between the two groups, with and without CMV infection, in terms of patient’s characteristics. The CMV infection, in patients receiving a transplanted organ from deceased donor, was significantly more prevalent than in those receiving kidney transplant from living donor (63% vs. 39%, respectively, P = 0.001. Recipients with HLA-B44 were more infected with CMV compared with patients without this allele (80% vs. 50%, respectively, P = 0.024; on the contrary, kidney recipients with HLA-DRB1-1 were less infected with CMV than patients without this allele (31% vs. 55%, respectively, P = 0.020. There was no significant relationship between CMV infection and other HLA alleles

  3. 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.

  4. Anti-cytomegalovirus activity of the anthraquinone atanyl blue PRL.

    Science.gov (United States)

    Alam, Zohaib; Al-Mahdi, Zainab; Zhu, Yali; McKee, Zachary; Parris, Deborah S; Parikh, Hardik I; Kellogg, Glen E; Kuchta, Alison; McVoy, Michael A

    2015-02-01

    Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC50 of 4.9μM but was cytotoxic at concentrations only twofold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238-265μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC50 of 6.3μM, significantly below its 50% cytotoxic concentration of 216μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to 1h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC50 of 4.5 and 9.3μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development.

  5. Impaired cellular immune response to tetanus toxoid but not to cytomegalovirus in effectively HAART-treated HIV-infected children.

    Science.gov (United States)

    Alsina, Laia; Noguera-Julian, Antoni; Fortuny, Clàudia

    2013-05-07

    Despite of highly active antiretroviral therapy, the response to vaccines in HIV-infected children is poor and short-lived, probably due to a defect in cellular immune responses. We compared the cellular immune response (assessed in terms of IFN-γ production) to tetanus toxoid and to cytomegalovirus in a series of 13 HIV-perinatally-infected children and adolescents with optimal immunovirological response to first line antiretroviral therapy, implemented during chronic infection. A stronger cellular response to cytomegalovirus (11 out of 13 patients) was observed, as compared to tetanus toxoid (1 out of 13; p=0.003). These results suggest that the repeated exposition to CMV, as opposed to the past exposition to TT, is able to maintain an effective antigen-specific immune response in stable HIV-infected pediatric patients and strengthen current recommendations on immunization practices in these children.

  6. Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

    Science.gov (United States)

    Bimber, Benjamin N.; Reed, Jason S.; Uebelhoer, Luke S.; Bhusari, Amruta; Hammond, Katherine B.; Klug, Alex; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus; Sacha, Jonah B.

    2016-01-01

    Cytomegaloviruses (CMV) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. Accordingly, full genome phylogenetic analysis of multiple new CMV field isolates derived from two closely related nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM), revealed distinct and tight lineage clustering according to the species of origin, with MCM CMV isolates mirroring the limited genetic diversity of their primate host that underwent a population bottleneck 400 years ago. Despite the ability of Rhesus CMV (RhCMV) laboratory strain 68–1 to replicate efficiently in MCM fibroblasts and potently inhibit antigen presentation to MCM T cells in vitro, RhCMV 68–1 failed to productively infect MCM in vivo, even in the absence of host CD8+ T and NK cells. In contrast, RhCMV clone 68–1.2, genetically repaired to express the homologues of the HCMV anti-apoptosis gene UL36 and epithelial cell tropism genes UL128 and UL130 absent in 68–1, efficiently infected MCM as evidenced by the induction of transgene-specific T cells and virus shedding. Recombinant variants of RhCMV 68–1 and 68–1.2 revealed that expression of either UL36 or UL128 together with UL130 enabled productive MCM infection, indicating that multiple layers of cross-species restriction operate even between closely related hosts. Cumulatively, these results implicate cell tropism and evasion of apoptosis as critical determinants of CMV transmission across primate species barriers, and extend the macaque model of human CMV infection and immunology to MCM, a nonhuman primate species with uniquely simplified host immunogenetics. PMID:27829026

  7. [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.

  8. 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.

  9. Refractory ulcerative colitis complicated by cytomegalovirus infection successfully treated with valganciclovir

    Directory of Open Access Journals (Sweden)

    Tiziana Larussa

    2012-11-01

    Full Text Available Cytomegalovirus (CMV infection is widespread in the general population. In patients with severe and/or steroid-refractory ulcerative colitis (UC, local reactivation of CMV can be detected in actively inflamed colonic tissue in approximately 30% of cases. However, the role of CMV in patients with UC is not clearly understood. There is evidence to show a possible role in exacerbating a colitis flare, whereas other studies describe CMV as an innocent bystander. We report the case of a patient with severe UC complicated by CMV infection who did not respond to conventional therapy. A complete diagnostic panel for CMV diagnosis, including tissue polymerase chain reaction and immunohistochemistry, was carried out. Three-week therapy with oral valganciclovir resulted in dramatic clinical and endoscopic improvement. Timing of diagnosis and treatment of CMV infection complicating UC is crucial in order to recognize the organ-disease and plan appropriate treatment.

  10. 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....

  11. Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients

    Directory of Open Access Journals (Sweden)

    Katharina Göhring

    2015-01-01

    Full Text Available In pediatric and adult patients after stem cell transplantation (SCT disseminated infections caused by human cytomegalovirus (HCMV can cause life threatening diseases. For treatment, the three antivirals ganciclovir (GCV, foscarnet (PFA and cidofovir (CDV are approved and most frequently used. Resistance to all of these antiviral drugs may induce a severe problem in this patient cohort. Responsible for resistance phenomena are mutations in the HCMV phosphotransferase-gene (UL97 and the polymerase-gene (UL54. Most frequently mutations in the UL97-gene are associated with resistance to GCV. Resistance against all three drugs is associated to mutations in the UL54-gene. Monitoring of drug resistance by genotyping is mostly done by PCR-based Sanger sequencing. For phenotyping with cell culture the isolation of HCMV is a prerequisite. The development of multidrug resistance with mutation in both genes is rare, but it is often associated with a fatal outcome. The manifestation of multidrug resistance is mostly associated with combined UL97/UL54-mutations. Normally, mutations in the UL97 gene occur initially followed by UL54 mutation after therapy switch. The appearance of UL54-mutation alone without any detection of UL97-mutation is rare. Interestingly, in a number of patients the UL97 mutation could be detected in specific compartments exclusively and not in blood.

  12. DIAGNOSIS OF CONGENITAL CYTOMEGALOVIRUS INFECTION IN HIGH RISK NEONATES

    Directory of Open Access Journals (Sweden)

    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

  13. Foix-Chavany-Marie syndrome in a 17-year-old female with congenital cytomegalovirus infection.

    Science.gov (United States)

    Conforti, Renata; Capasso, Raffaella; Capaldo, Guglielmo; Dato, Clemente; Saracino, Dario; Di Iorio, Giuseppe; Melone, Mariarosa A

    2014-01-01

    Foix-Chavany-Marie syndrome is characterized by bilateral facio-glosso-pharyngo-masticatory paralysis of voluntary movement due to bilateral anterior opercular lesions. We describe the case of a 17-year-old female affected by Foix-Chavany-Marie syndrome and congenital cytomegalovirus infection, evaluating the possible etiopathogenetic correlation between cerebral cortical dysplasia and intrauterine infections.

  14. 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.

  15. Pathogenesis of formation of frequent respiratory infections in children with Epstein-Barr virus and cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    I. V. Babachenko

    2011-01-01

    Full Text Available The goal was to clarify the pathogenesis of the formation of frequent respiratory infections in children with Epstein-Barr virus and cytomegalovirus infection on the basis of studying the microbial landscape of anti-infective and mucous membranes of the oropharynx resistance. The results of clinical and laboratory examination of 47 frequently and chronically ill children aged 6 months to 7 years with active Epstein-Barr virus and / or cytomegalovirus infection are presented. 19 children (40,4% had mono-CMV infection, 6 patients (12,8% – Mono-Epstein – Barr virus nfection, 22 children (46,8% – mixed herpesvirus infections. The carrier state of S. рneumoniae was revealed in 70,0% of cases, the carrier state of S. aureus – in 40,5% of cases against the background of decrease normal mouth microflora. Deficiency of nonspecific secretory immunoglobulin class A was established in 98% of cases, destructive changes of epiteliotsits on a mucous membrane of an oral cavity children was established in 93,9 % of cases. The presence of eosinophils in the mucosa of the oropharynx was reported in 29,8% of patients, in 78,7% of patients – the presence of polymorphonuclear leukocytes of more than 5 cells in a field of view. A scheme of the pathogenesis of recurrent respiratory diseases in often long-term ill children is desined.

  16. Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival

    NARCIS (Netherlands)

    Smelt, M. J.; Faas, M. M.; Melgert, B. N.; de Vos, P.; de Haan, Bart; de Haan, Aalzen

    2011-01-01

    Transplantation of pancreatic islets is a promising therapy for the treatment of type 1 diabetes mellitus. However, long-term islet graft survival rates are still unsatisfactory low. In this study we investigated the role of cytomegalovirus (CMV) in islet allograft failure. STZ-diabetic rats receive

  17. 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

  18. Clinical and morphological variants of hepatitis onset with congenital cytomegalovirus and hepatitis C infection

    Directory of Open Access Journals (Sweden)

    R. A. Ushakova

    2013-01-01

    Full Text Available We present comparative analysis of clinical – morphological data from infants with congenital cytomegalovirus and hepatitis C infection. 97 patients with hepatitis underwent a standard set of clinical and laboratory tests. ELISA and PCR were used to verify infectious agents. Informed consent to perform a liver biopsy was obtained from the parents of 28 children. immunohistochemical test of the liver samples managed to identify markers of cytomegalovirus (protein pp65 and p52 and hepatitis C (helicase NS3. The hepatitis C virus was detected in 41 patients: 3a genotype – 68.3%, 1b –31.7% respectively. Congenital hepatitis C onset presents itself as mild and atypical and causes chronic hepatitis with the 1st degree fibrosis. Cytomegalovirus replication markers were found in 56 children. The most common manifestations of hepatitis associated with cytomegalovirus infection are prolonged jaundice, cholestasis, gepatolienalny syndrome, early onset of the disease with increased transaminase levels and dominance in AST. Structural changes of the liver are characterized by the presence of inflammatory infiltration, cholestasis with duktulopenia, lobular structure damage. Congenital cytomegalovirus-related hepatitis is likely to result in liver cirrhosis and is associated with poor prognosis.

  19. 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

  20. 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.

  1. Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state

    OpenAIRE

    2015-01-01

    © 2015, Journal of NeuroVirology, Inc. Cytomegalovirus (CMV) is the most common cause of congenital infection in developed countries and a major cause of neurological disability in children. Although CMV can affect multiple organs, the most important sequelae of intrauterine infection are related to lesions of the central nervous system. However, little is known about the pathogenesis and the cellular events responsible for neuronal damage in infants with congenital infection. Some studies ha...

  2. Maternal cytomegalovirus infection prevention: the role of Dutch primary care midwives.

    NARCIS (Netherlands)

    Pereboom, M.T.R.; Manniën, J.; Spelten, E.R.; Hutton, E.K.; Schellevis, F.G.

    2014-01-01

    Objective: to assess the knowledge of cytomegalovirus (CMV) infection among Dutch primary care midwives, and clinical approaches to informing women about CMV. Design: cross-sectional study, using self-administered questionnaires. Participants: 330 Dutch primary care midwives. Setting: primary midwif

  3. 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.

  4. Susceptibility of Human Pancreatic beta Cells for Cytomegalovirus Infection and the Effects on Cellular Immunogenicity

    NARCIS (Netherlands)

    Smelt, M.J.; Faas, M.M.; de Haan, Bart; Draijer, C.; Hugenholtz, G.C.G.; de Haan, A.; Engelse, M.A.; de Koning, E.J.P.; de Vos, P.

    2012-01-01

    Objectives: Human cytomegalovirus (HCMV) infection has been suggested to be a causal factor in the development of type 1 diabetes, posttransplantation diabetes, and the failure of islet allografts. This effect of CMV has been interpreted as an indirect effect on the immune system rather than direct

  5. 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.

  6. 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...

  7. 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

  8. Cytomegalovirus Infection following Kidney Transplantation: a Multicenter Study of 3065 Cases

    OpenAIRE

    2012-01-01

    Background: Cytomegalovirus (CMV) infection is a common complication following kidney transplantation. Objective: To assess the incidence and risk factors of CMV infection among renal transplant recipients. Methods: In a retrospective multicenter study, 3065 renal transplant recipients from 17 transplant centers of Iran were studied between April 2008 and January 2011. Kidney transplant patients were routinely monitored by sequential blood samples drawn for use in the CMV-pp65 antigenemia ass...

  9. 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.

  10. 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)

  11. 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.

  12. Characterization of Cytomegalovirus Lung Infection in Non-HIV Infected Children

    Directory of Open Access Journals (Sweden)

    Sonia M. Restrepo-Gualteros

    2014-05-01

    Full Text Available Cytomegalovirus (CMV is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years, using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%, hypoxemia (100%, diffuse adventitious breath sounds (100% and increased respiratory effort (93%. All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate or histology/immunohistochemistry in lung biopsy (100% detection rate. CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. Conclusion: CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes.

  13. [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.

  14. 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.

  15. 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.

  16. Human cytomegalovirus IE2 protein interacts with transcription activating factors

    Institute of Scientific and Technical Information of China (English)

    XU; Jinping(徐进平); YE; Linbai(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.

  17. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials

    DEFF Research Database (Denmark)

    Ljungman, Per; Boeckh, Michael; Hirsch, Hans H

    2016-01-01

    Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2002...... research and drug development. The main changes compared to previous definitions are the introduction of a "probable disease" category and to incorporate quantitative nucleic acid testing in some end-organ disease categories. As the field evolves, the need for updates of these definitions is clear...

  18. Association of TLR3 L412F Polymorphism with Cytomegalovirus Infection in Children

    Science.gov (United States)

    Studzińska, Mirosława; Jabłońska, Agnieszka; Wiśniewska-Ligier, Małgorzata; Nowakowska, Dorota; Gaj, Zuzanna; Leśnikowski, Zbigniew J.; Woźniakowska-Gęsicka, Teresa; Wilczyński, Jan; Paradowska, Edyta

    2017-01-01

    Intracellular Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) and activates antiviral immune responses through the production of type I interferons (IFNs) and inflammatory cytokines. This receptor binds to dsRNA molecules produced during human cytomegalovirus (HCMV) replication. TLR7 senses viral single-stranded RNA (ssRNA) in endosomes, and it can interact with endogenous RNAs. We determined the genotype distribution of single-nucleotide polymorphisms (SNPs) within the TLR3 and TLR7 genes in children with HCMV infection and the relationship between TLR polymorphisms and viral infection. We genotyped 59 children with symptomatic HCMV infection and 78 healthy individuals for SNPs in the TLR3 (rs3775290, c.1377C>T, F459F; rs3775291, c.1234C>T, L412F; rs3775296, c.-7C>A) and TLR7 (rs179008, c.32A>T, Q11L; rs5741880, c.3+1716G>T) genes. SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and capillary electrophoresis. The HCMV DNA load was quantified by real-time PCR. We found an increased frequency of the heterozygous genotype TLR3 L412F in children with HCMV infection compared with uninfected cases. In individuals with a mutation present in at least one allele of the L412F SNP, an increased risk of HCMV disease was found, and this result remained highly significant after Bonferroni’s correction for multiple testing (Pc < 0.001). The heterozygous genotype of this SNP was associated with the increased risk of HCMV disease in an adjusted model that included the HCMV DNA copy number in whole blood and urine (P < 0.001 and P = 0.008, respectively). Moreover, those with a heterozygous genotype of rs3775296 showed an increased relative risk of HCMV infection (P = 0.042), but this association did not reach statistical significance after correction for multiple testing. In contrast, the rs3775290 SNP of TLR3 and TLR7 SNPs were not related to viral infection. A moderate linkage

  19. Lymphotropic Herpesvirus infection and malignant lymphoma, immunological aspects of cytomegalovirus and Epstein- Barr virus infections

    NARCIS (Netherlands)

    Napel, Christianus Hubertus Henricus ten

    1979-01-01

    In de voorgaande hoofdstukken van dit proefschrift werd de oorspronkelijke chronologische volgorde van het onderzoek aangehouden. Maar in dit deel wordt hiervan afgeweken en zullen de resultaten worden samengevat en besproken volgens onderstaande indeling: 1. Cytomegalovirus( CMV)-specifieke immuunr

  20. Murine cytomegalovirus infection of neural stem cells alters neurogenesis in the developing brain.

    Directory of Open Access Journals (Sweden)

    Manohar B Mutnal

    Full Text Available BACKGROUND: Congenital cytomegalovirus (CMV brain infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital brain infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV and the pattern of injury to the developing brain. METHODOLOGY/PRINCIPAL FINDINGS: We used our MCMV infection model and a multi-color flow cytometry approach to quantify the effect of viral infection on the developing brain, identifying specific target cells and the consequent effect on neurogenesis. In this study, we show that neural stem cells (NSCs and neuronal precursor cells are the principal target cells for MCMV in the developing brain. In addition, viral infection was demonstrated to cause a loss of NSCs expressing CD133 and nestin. We also showed that infection of neonates leads to subsequent abnormal brain development as indicated by loss of CD24(hi cells that incorporated BrdU. This neonatal brain infection was also associated with altered expression of Oct4, a multipotency marker; as well as down regulation of the neurotrophins BDNF and NT3, which are essential to regulate the birth and differentiation of neurons during normal brain development. Finally, we report decreased expression of doublecortin, a marker to identify young neurons, following viral brain infection. CONCLUSIONS: MCMV brain infection of newborn mice causes significant loss of NSCs, decreased proliferation of neuronal precursor cells, and marked loss of young neurons.

  1. 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

  2. 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.

  3. The DNA damage response induced by infection with human cytomegalovirus and other viruses.

    Science.gov (United States)

    Xiaofei, E; Kowalik, Timothy F

    2014-05-23

    Viruses use different strategies to overcome the host defense system. Recent studies have shown that viruses can induce DNA damage response (DDR). Many of these viruses use DDR signaling to benefit their replication, while other viruses block or inactivate DDR signaling. This review focuses on the effects of DDR and DNA repair on human cytomegalovirus (HCMV) replication. Here, we review the DDR induced by HCMV infection and its similarities and differences to DDR induced by other viruses. As DDR signaling pathways are critical for the replication of many viruses, blocking these pathways may represent novel therapeutic opportunities for the treatment of certain infectious diseases. Lastly, future perspectives in the field are discussed.

  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. 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

  6. Accuracy of the serological ELISA test compared with the polymerase chain reaction for the diagnosis of cytomegalovirus infection in pregnancy

    Directory of Open Access Journals (Sweden)

    Silvana Varella Parmigiani

    Full Text Available CONTEXT: The most frequently used methods for detecting antibodies are the indirect immunofluorescence test and the enzymatic immunoassay (ELISA. The polymerase chain reaction is a molecular biology technique in which the production of large amounts of specific DNA fragments is induced from very low concentrations of complex substrates aloowing the detection of very low amounts of viral particles. OBJECTIVE: To assess the accuracy of serological/ELISA tests in comparison with the polymerase chain reaction in maternal blood to diagnose cytomegalovirus infection. DESIGN: A descriptive study was performed. SETTING: High-risk outpatient clinic of Campinas University (Unicamp. PARTICIPANTS: We selected 243 pregnant women. All of them had been indicated for blood sampling because of suspicions of cytomegalovirus infection and also because of other infections. MAIN MEASUREMENTS: The group was tested for cytomegalovirus. Serological tests were run and compared to the polymerase chain reaction, which was considered to be the gold standard. Status analyses were done using Fisher's exact test, via the SAS software. RESULTS: The previous cytomegalovirus infection rate was 94.6%. The main reasons for inclusion in the study were fetal nervous system malformation (25.5%, maternal toxoplasmosis (25.5% and Rh isoimmunization (14.8%. Only two women were included because of positive serological immunoglobulin M test for cytomegalovirus. The sensitivity and specificity of the serological tests were 94% and 6% for immunoglobulin G. CONCLUSION: Serological tests had lower sensitivity in comparison with the polymerase chain reaction test when diagnosing cytomegalovirus infection. The consequences of positive polymerase chain reaction and negative immunoglobulin M in women remain unknown.

  7. 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

  8. 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...... aged 73-94 years were included (n=302 pairs). Offspring of the long-lived LLS participants had significantly lower seroprevalence of CMV compared to their partners (offspring: 42% vs. partners: 51%, P=0·003). Of 372 offspring living with a CMV-positive partner, only 58% were infected. The corresponding...... number for partners was 71% (P

  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. Relationship between TLR4 signalling alterations and effective human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  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. Combination antiviral therapy for ganciclovir-resistant cytomegalovirus infection in solid-organ transplant recipients.

    Science.gov (United States)

    Mylonakis, Eleftherios; Kallas, Wendy M; Fishman, Jay A

    2002-05-15

    The resistance of cytomegalovirus (CMV) to ganciclovir is a factor in therapeutic failure and disease progression. The clinical significance of such resistance in solid-organ transplantation has not been completely established. Six patients who developed persistent infection due to ganciclovir-resistant CMV were treated with a combination of ganciclovir (50% of the therapeutic dose) and a daily dose of intravenous foscarnet that gradually increased to a maximum of 125 mg/kg. All patients responded clinically within 72-96 hours. Magnesium depletion occurred in all patients. No clinical or laboratory relapses have been observed in 6-30 months of follow-up. Gradually increasing doses of foscarnet combined with half-dose regimens of ganciclovir are safe and can be beneficial in organ transplant recipients with ganciclovir-resistant CMV infection. Larger studies are needed to identify the patients who are most likely to benefit from this regimen.

  14. 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.

  15. 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.

  16. Permissive human cytomegalovirus infection of a first trimester extravillous cytotrophoblast cell line

    Directory of Open Access Journals (Sweden)

    LaMarca Heather L

    2004-11-01

    Full Text Available Abstract Human cytomegalovirus (HCMV is the leading cause of congenital viral infection in the United States and Europe. Despite the significant morbidity associated with prenatal HCMV infection, little is known about how the virus infects the fetus during pregnancy. To date, primary human cytotrophoblasts (CTBs have been utilized to study placental HCMV infection and replication; however, the minimal mitotic potential of these cells restricts experimentation to a few days, which may be problematic for mechanistic studies of the slow-replicating virus. The aim of this study was to determine whether the human first trimester CTB cell line SGHPL-4 was permissive for HCMV infection and therefore could overcome such limitations. HCMV immediate early (IE protein expression was detected as early as 3 hours post-infection in SGHPL-4 cells and progressively increased as a function of time. HCMV growth assays revealed the presence of infectious virus in both cell lysates and culture supernatants, indicating that viral replication and the release of progeny virus occurred. Compared to human fibroblasts, viral replication was delayed in CTBs, consistent with previous studies reporting delayed viral kinetics in HCMV-infected primary CTBs. These results indicate that SGHPL-4 cells are fully permissive for the complete HCMV replicative cycle. Our findings suggest that these cells may serve as useful tools for future mechanistic studies of HCMV pathogenesis during early pregnancy.

  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. Viral Interleukin-10 Expressed by Human Cytomegalovirus during the Latent Phase of Infection Modulates Latently Infected Myeloid Cell Differentiation ▿ †

    OpenAIRE

    Avdic, Selmir; Cao, John Z.; Cheung, Allen K.L.; Abendroth, Allison; Slobedman, Barry

    2011-01-01

    The human cytomegalovirus UL111A gene is expressed during latent and productive infections, and it codes for homologs of interleukin-10 (IL-10). We examined whether viral IL-10 expressed during latency altered differentiation of latently infected myeloid progenitors. In comparison to infection with parental virus or mock infection, latent infection with a virus in which the gene encoding viral IL-10 has been deleted upregulated cytokines associated with dendritic cell (DC) formation and incre...

  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. Thrombosis associated with cytomegalovirus infection in patients with ANCA-positive vasculitis.

    Science.gov (United States)

    Wolf, G; Porth, J; Stahl, R A

    2001-11-01

    Three cases of venous thrombosis with pulmonary embolism in two patients associated with underlying antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis and reactivated cytomegalovirus (CMV) infection are described. In vitro studies previously have shown that infection of endothelium with CMV increases the release of procoagulant factors and stimulates the expression of adhesion molecules. Because the endothelial cell plays a pivotal role in maintaining the equilibrium between procoagulant and anticoagulant states, injury by ANCA-positive vasculitis and additional infection with CMV may ignite a local thrombosis easily. Although venous thrombosis is uncommon in CMV infection (eg, in the immunosuppressed state after organ transplantation), the combination of vasculitis and reactivated CMV infection may have contributed to injury of the vessel wall with subsequent development of thrombosis. A better awareness of this association could improve morbidity and may lead to prevention of potentially life-threatening pulmonary embolism. Patients with ANCA-positive vasculitis and CMV infection may profit from prophylactic anticoagulant therapy with heparin or low-molecular-weight heparin.

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

    Science.gov (United States)

    Tirosh, Osnat; Cohen, Yifat; Shitrit, Alina; Shani, Odem; Le-Trilling, Vu Thuy Khanh; Trilling, Mirko; Friedlander, Gilgi; Tanenbaum, Marvin; Stern-Ginossar, Noam

    2015-01-01

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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 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.

  5. Dual Role of Natural Killer Cells on Graft Rejection and Control of Cytomegalovirus Infection in Renal Transplantation

    Science.gov (United States)

    López-Botet, Miguel; Vilches, Carlos; Redondo-Pachón, Dolores; Muntasell, Aura; Pupuleku, Aldi; Yélamos, José; Pascual, Julio; Crespo, Marta

    2017-01-01

    Allograft rejection constitutes a major complication of solid organ transplantation requiring prophylactic/therapeutic immunosuppression, which increases susceptibility of patients to infections and cancer. Beyond the pivotal role of alloantigen-specific T cells and antibodies in the pathogenesis of rejection, natural killer (NK) cells may display alloreactive potential in case of mismatch between recipient inhibitory killer-cell immunoglobulin-like receptors (KIRs) and graft HLA class I molecules. Several studies have addressed the impact of this variable in kidney transplant with conflicting conclusions; yet, increasing evidence supports that alloantibody-mediated NK cell activation via FcγRIIIA (CD16) contributes to rejection. On the other hand, human cytomegalovirus (HCMV) infection constitutes a risk factor directly associated with the rate of graft loss and reduced host survival. The levels of HCMV-specific CD8+ T cells have been reported to predict the risk of posttransplant infection, and KIR-B haplotypes containing activating KIR genes have been related with protection. HCMV infection promotes to a variable extent an adaptive differentiation and expansion of a subset of mature NK cells, which display the CD94/NKG2C-activating receptor. Evidence supporting that adaptive NKG2C+ NK cells may contribute to control the viral infection in kidney transplant recipients has been recently obtained. The dual role of NK cells in the interrelation of HCMV infection with rejection deserves attention. Further phenotypic, functional, and genetic analyses of NK cells may provide additional insights on the pathogenesis of solid organ transplant complications, leading to the development of biomarkers with potential clinical value. PMID:28261220

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Trip to immunity: resistant cytomegalovirus infection in a lung transplant recipient

    Directory of Open Access Journals (Sweden)

    Nikolaus Kneidinger

    2014-11-01

    Full Text Available We report the case of a young female lung transplant recipient with difficult-to-treat cytomegalovirus (CMV disease. While treatment with intravenous (IV ganciclovir failed due to antiviral drug resistance, a trial with foscarnet resulted in severe side effects. In addition, the patient received IV CMV-specific immune globulins as adjunctive therapy and leflunomide as experimental therapy. In this context, CMV-specific immune monitoring was performed and was successfully implemented in management decisions. The patient was screened for acquisition of an adaptive immune response, and antiviral prophylaxis and therapy was tailored according to results. This report highlights the impact of CMV-specific immune monitoring on individualized therapy for appropriate prophylaxis and management of CMV infection and diseases.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Immune Restoration Syndrome with disseminated Penicillium marneffei and Cytomegalovirus co-infections in an AIDS patient

    Directory of Open Access Journals (Sweden)

    Wig Naveet

    2007-10-01

    Full Text Available Abstract Background Penicillium marneffei is a dimorphic fungus, endemic in South-east Asia. The fungus causes severe disease in immunocompromised patients such as AIDS. However, no case of immune restoration disease of Penicillium marneffei is reported in literature from a non-endemic area. Case Presentation We report the first case of Penicillium marneffei and Cytomegalovirus infection manifesting as a result of immune restoration one month after initiating HAART. This severely immunocompromised patient had presented with multiple lymphadenopathy, massive hepatosplenomegaly, visual impairment and mild icterus, but no skin lesions. Penicillium marneffei was isolated from lymph node fine-needle aspirates and blood cultures. Conclusion In order to diagnose such rare cases, the clinicians, histopathologists and microbiologists alike need to maintain a strong index of suspicion for making initial diagnosis as well as for suspecting immune reconstitution syndrome (IRS with Penicillium marneffei.

  15. Immune Restoration Syndrome with disseminated Penicillium marneffei and Cytomegalovirus co-infections in an AIDS patient

    Science.gov (United States)

    Gupta, Swati; Mathur, Purva; Maskey, Dipesh; Wig, Naveet; Singh, Sarman

    2007-01-01

    Background Penicillium marneffei is a dimorphic fungus, endemic in South-east Asia. The fungus causes severe disease in immunocompromised patients such as AIDS. However, no case of immune restoration disease of Penicillium marneffei is reported in literature from a non-endemic area. Case Presentation We report the first case of Penicillium marneffei and Cytomegalovirus infection manifesting as a result of immune restoration one month after initiating HAART. This severely immunocompromised patient had presented with multiple lymphadenopathy, massive hepatosplenomegaly, visual impairment and mild icterus, but no skin lesions. Penicillium marneffei was isolated from lymph node fine-needle aspirates and blood cultures. Conclusion In order to diagnose such rare cases, the clinicians, histopathologists and microbiologists alike need to maintain a strong index of suspicion for making initial diagnosis as well as for suspecting immune reconstitution syndrome (IRS) with Penicillium marneffei. PMID:17922912

  16. 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...... and chromatin immunoprecipitation assays. Due to the key role of PPARgamma in placentation and its specific trophoblast expression within the human placenta, we then provided evidence that by activating PPARgamma human cytomegalovirus dramatically impaired early human trophoblast migration and invasiveness......, as assessed by using well-established in vitro models of invasive trophoblast i.e. primary cultures of EVCT isolated from first trimester placentas and the EVCT-derived cell line HIPEC. Our data provide new clues to explain how early infection during pregnancy could impair implantation, placentation...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Vescovini, Rosanna; Telera, Anna Rita; Pedrazzoni, Mario; Abbate, Barbara; Rossetti, Pietro; Verzicco, Ignazio; Arcangeletti, Maria Cristina; Medici, Maria Cristina; Calderaro, Adriana; Volpi, Riccardo; Sansoni, Paolo; Fagnoni, Francesco Fausto

    2016-01-01

    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. PMID:26990192

  1. Congenital cytomegalovirus infection: contribution and best timing of prenatal MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Cannie, Mieke M. [University Hospital Brugmann, Universite Libre de Bruxelles, Department of Radiology, Brussels (Belgium); UZ Brussel, Vrije Universiteit Brussel, Department of Radiology, Brussel (Belgium); Devlieger, Roland; Catte, Luc de; Valk, Elise van der [University Hospitals Leuven, Department of Obstetrics and Gynecology, Leuven (Belgium); Leyder, Mina; Foulon, Walter [UZ Brussel, Vrije Universiteit Brussel, Department of Obstetrics, Brussel (Belgium); Claus, Filip [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Onze-Lieve-Vrouw Hospital, Department of Radiology, Aalst (Belgium); Leus, Astrid [UZ Brussel, Vrije Universiteit Brussel, Department of Radiology, Brussel (Belgium); Cossey, Veerle [University Hospitals Leuven, Neonatal Intensive Care Unit, Leuven (Belgium); Foulon, Ina [UZ Brussel, Vrije Universiteit Brussel, Department of Otolaryngology - Head and Neck Surgery, Brussel (Belgium); Cos, Teresa; Jani, Jacques C. [University Hospital Brugmann, Universite Libre de Bruxelles, Department of Obstetrics and Gynecology, Brussels (Belgium); Bernaert, Anja [Sint-Augustinus Hospital, Department of Radiology, Antwerp (Belgium); Oyen, Raymond [University Hospitals Leuven, Department of Radiology, Leuven (Belgium)

    2016-10-15

    To predict sensorineural hearing loss (SNHL) and neurological impairment in congenital cytomegalovirus (cCMV) infection using MR imaging and define the best timing in pregnancy for prenatal assessment. In 121 patients with confirmed cCMV infection, brain features at MR imaging were respectively graded from 1 to 5: normal; isolated frontal/parieto-occipital hyperintensity; temporal periventricular hyperintensity; temporal/occipital cysts and/or intraventricular septa; migration disorders. Grading was correlated with postnatal SNHL and neurological impairment using regression analysis. In 51 fetuses with MR examinations at 26.9 and 33.0 weeks, the predictive value of SNHL and neurological impairment was compared using ROC curves. Postnatal follow-up showed SNHL in 18 infants and neurological impairment in 10. MR grading was predictive of SNHL and of neurological impairment (P < 0.001). In grade 1 or 2, none had SNHL and 1/74 had neurological impairment. The areas under ROC curves for prediction of postnatal SNHL and of neurological impairment from first and second MR examination were comparable. Our data suggest that in cCMV infection, prediction of SNHL and neurological impairment is feasible by fetal MR imaging with a high negative predictive value and can equally be done at 27 or 33 weeks of gestation. (orig.)

  2. Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease.

    Science.gov (United States)

    Lurain, Nell S; Hanson, Barbara A; Martinson, Jeffrey; Leurgans, Sue E; Landay, Alan L; Bennett, David A; Schneider, Julie A

    2013-08-15

    Serum, cerebrospinal fluid (CSF), and cryopreserved lymphocytes from subjects in the Rush Alzheimer's Disease Center Religious Orders Study were analyzed for associations between cytomegalovirus (CMV) infection and clinical and pathological markers of Alzheimer disease. CMV antibody levels were associated with neurofibrillary tangles (NFTs). CSF interferon γ was only detected in seropositive subjects and was significantly associated with NFTs. The percentage of senescent T cells (CD4+ or CD8+CD28-CD57+) was significantly higher for CMV-seropositive as compared to CMV-seronegative subjects and was marginally associated with the pathologic diagnosis of Alzheimer disease (CD4+) or amyloid-β (CD8+). Immunocytochemical analysis showed induction of amyloid-β in human foreskin fibroblasts (HFFs) infected with each of 3 clinical CMV strains. In the same subjects, there was no association of herpes simplex virus type 1 (HSV-1) antibody levels with CMV antibody levels or clinical or pathological markers of Alzheimer disease. HSV-1 infection of HFFs did not induce amyloid-β. These data support an association between CMV and the development of Alzheimer disease.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Cidofovir Activity against Poxvirus Infections

    Directory of Open Access Journals (Sweden)

    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.

  5. Cidofovir Activity against Poxvirus Infections.

    Science.gov (United States)

    Andrei, Graciela; Snoeck, Robert

    2010-12-01

    Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, 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.

  6. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alcendor Donald J

    2012-05-01

    Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

  7. Clinical study on cytomegalovirus infection after hematopoietic stem cell transplantation in 26patients with primary immunodeficiency diseases

    Institute of Scientific and Technical Information of China (English)

    阙蜜

    2014-01-01

    Objective To explore the risk factors,and control measures of cytomegalovirus(CMV)infection after hematopoietic stem cell transplantation(HSCT)in children with primary immunodeficiency diseases(PID).Methods We retrospectively analyzed the results of 26 patients with PID-Wiskott-Aldrich syndrome(WAS,n=20),severe combined immunodeficiency(SCID,n=1),Xlinked chronic granulomatous disease(XCGD,n=2)and X-linked hyper-immunoglobulin M(Ig M)syndrome

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  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. Cytomegalovirus Infection following Kidney Transplantation: a Multicenter Study of 3065 Cases

    Science.gov (United States)

    Einollahi, B.

    2012-01-01

    Background: Cytomegalovirus (CMV) infection is a common complication following kidney transplantation. Objective: To assess the incidence and risk factors of CMV infection among renal transplant recipients. Methods: In a retrospective multicenter study, 3065 renal transplant recipients from 17 transplant centers of Iran were studied between April 2008 and January 2011. Kidney transplant patients were routinely monitored by sequential blood samples drawn for use in the CMV-pp65 antigenemia assay, and for hematological and biochemistry tests. Results: 63% of studied patients were males; the mean±SD age of participants was 38±15 years. The majority of cases (81%) received a kidney from a living unrelated donor (LURD), 9% from living related donor (LRD), and 10% from deceased donors. 671 patients experienced CMV viremia. The incidence of CMV infection was 21.9% (95% CI: 20.4%–23.4%). The rate was higher in the first 6 months after transplantation (p<0.001); in recipients with higher level of cyclosporine (p<0.001); in those with lower hemoglobin concentration (p=0.02); patients with elevated ALT (p<0.001); those with increased fasting blood sugar (p=0.005); recipients with dyslipidemia (p<0.05); deceased kidney recipients (p=0.006); and patients with kidney graft impairment (p=0.01). In multivariate regression analysis, time since kidney transplantation (p<0.001) and renal allograft failure (p<0.001) were the only risk factors associated with CMV infection. Conclusions: CMV infection was a common complication in the first 6 months of kidney transplantation, particularly among patients with kidney graft impairment. PMID:25013626

  12. 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.

  13. Cytomegalovirus reactivation after low-dose steroid treatment for hemolytic anemia in a patient with primary Epstein-Barr virus infection.

    Science.gov (United States)

    Troselj-Vukic, Biserka; Milotic, Irena; Milotic, Franko; Crnic-Martinovic, Marija; Grahovac, Blazenka

    2007-01-01

    Cytomegalovirus reactivation is a well described event occurring after intensive therapeutic suppression of the immune function in patients with latent infection. Treatment protocols for suppression of the immune response often include high-dose steroids. However, it is not known whether even a low-dose steroid treatment can reactivate latent cytomegalovirus in otherwise healthy persons. We documented cytomegalovirus reactivation after low-dose steroid treatment for autoimmune hemolytic anemia as a complication of Epstein-Barr virus mononucleosis in an immunocompetent 21-year-old man.

  14. How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients

    Science.gov (United States)

    El Chaer, Firas; Shah, Dimpy P.

    2016-01-01

    Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy. CMV resistance is diagnosed by detecting specific genetic mutations. UL97 mutations confer resistance to ganciclovir and valganciclovir, and a UL54 mutation confers multidrug resistance. Risk factors for resistance include prolonged or previous anti-CMV drug exposure or inadequate dosing, absorption, or bioavailability. Host risk factors include type of HCT and degree of immunosuppression. Depending on the genotyping results, multiple strategies can be adopted to treat resistant CMV infections, albeit no randomized clinical trials exist so far, after reducing immunosuppression (if possible): ganciclovir dose escalation, ganciclovir and foscarnet combination, and adjunct therapy such as CMV-specific cytotoxic T-lymphocyte infusions. Novel therapies such as maribavir, brincidofovir, and letermovir should be further studied for treatment of resistant CMV. PMID:27760756

  15. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Stahl, Felix R; Heller, Katrin; Halle, Stephan; Keyser, Kirsten A; Busche, Andreas; Marquardt, Anja; Wagner, Karen; Boelter, Jasmin; Bischoff, Yvonne; Kremmer, Elisabeth; Arens, Ramon; Messerle, Martin; Förster, Reinhold

    2013-01-01

    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.

  19. Annexin 2-mediated enhancement of cytomegalovirus infection opposes inhibition by annexin 1 or annexin 5.

    Science.gov (United States)

    Derry, Mélanie C; Sutherland, Michael R; Restall, Christina M; Waisman, David M; Pryzdial, Edward L G

    2007-01-01

    Biochemical studies have suggested that annexin 2 (A2) may participate in cytomegalovirus (CMV) infection. In the current work, effects of A2 monomer (p36) and heterotetramer (A2t; p36(2)p11(2)) were investigated. Demonstrating a role for endogenous A2, the four stages of infection that were followed were each inhibited by anti-p36 or anti-p11 at 37 degrees C. Immuno-inhibition was attenuated when the virus and cells were pre-incubated at 4 degrees C to coordinate virus entry initiated afterwards at 37 degrees C, reconciling controversy in the literature. As an explanation, CMV-induced phosphorylation of p36 was prevented by the 4 degrees C treatment. Supporting these immuno-inhibition data, purified A2t or p11 increased CMV infectious-progeny generation and CMV gene expression. A specific role for A2t was indicated by purified p36 having no effect. Unlike other steps, primary plaque formation was not enhanced by purified A2t or p11, possibly because of undetectable phosphorylation. As annexins 1 (A1) and 5 (A5) interact with A2, their effect on CMV was also tested. Both purified proteins inhibited CMV infection. In each experiment, the concentration of A1 required for half-maximal inhibition was five- to 10-fold lower than that of A5. Addition of A2 opposed A1- or A5-mediated inhibition of CMV, as did certain A2-specific antibodies that had no effect in the absence of added A1 or A5. Transfection of the p36-deficient cell line HepG2 increased CMV infection and was required for inhibition by the other annexins. These data suggest that CMV exploits A2t at physiological temperature to oppose the protection of cells conferred by A1 or A5.

  20. Infections

    Science.gov (United States)

    ... Infections Adenovirus Bronchiolitis Campylobacter Infections Cat Scratch Disease Cellulitis Chickenpox Chlamydia Cold Sores Common Cold Coxsackievirus Infections Croup Cytomegalovirus (CMV) Dengue Fever Diphtheria E. Coli ...

  1. Deregulation of type I IFN-dependent genes correlates with increased susceptibility to cytomegalovirus acute infection of dicer mutant mice.

    Directory of Open Access Journals (Sweden)

    Eleonore Ostermann

    Full Text Available Regulation of gene expression by microRNAs (miRNAs is now considered as an essential mechanism for cell development and homeostasis. Indeed, numerous studies have reported that modulating their expression, maturation, or activity can affect cell survival, identity or activation. In particular, miRNAs are key players in the tight regulation of signaling cascades, and as such, they appear as perfectly suited immunomodulators. Several immune-related processes, including inflammation, have recently been demonstrated to require specific miRNAs. In addition, the discovery of herpesvirus-encoded miRNAs has reinforced this assumption. To decipher the potential roles of miRNAs in innate antiviral immune response, we developed an in vivo model based on the inoculation of mouse cytomegalovirus (MCMV in mice. Furthermore, we exploited a mouse line carrying a hypomorphic mutation in the Dicer gene to visualize the impact of impaired miRNA biogenesis upon the anti-MCMV response. Our data indicate that miRNAs are important actors in mounting an efficient response against herpesviruses. We suggest that a rapid and transient interferon response following viral infection requires miRNA-dependent repressor release. In addition, our in vivo efforts identified several miRNA targets, thus providing a conceptual framework for future analyzes on the regulation of specific actors involved in the Type I interferon pathway.

  2. Successful low-dose leflunomide treatment for ganciclovir-resistant cytomegalovirus infection with high-level antigenemia in a kidney transplant: A case report and literature review.

    Science.gov (United States)

    Morita, Shinya; Shinoda, Kazunobu; Tamaki, Satoshi; Kono, Hidaka; Asanuma, Hiroshi; Nakagawa, Ken; Oya, Mototsugu

    2016-09-01

    Ganciclovir-resistant cytomegalovirus infection is sometimes life-threatening for organ transplant recipients. Foscarnet is an alternative, although it may potentially worsen the preexistent impaired renal function. Here we report the case of a successful low-dose leflunomide treatment in a kidney transplant recipient with very high viral replication, who underwent kidney transplantation 10 years before. Administering 10mg leflunomide daily for 5 months without a loading dose completely cleared the ganciclovir-resistant cytomegalovirus strains.

  3. Life-threatening intracranial bleeding in a newborn with congenital cytomegalovirus infection: late-onset neonatal hemorrhagic disease.

    Science.gov (United States)

    Dallar, Yildiz; Tiras, Ulku; Catakli, Tulin; Gulal, Gonul; Sayar, Yavuz; Selvar, Beray; Alioglu, Bulent

    2011-02-01

    The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.

  4. 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.

  5. Ultrastructural Pathology of Murine Cytomegalovirus Infection in Cultured Mouse Nervous System Tissue

    Science.gov (United States)

    Willson, Nicholas J.; Schneider, Joseph F.; Rosen, Moshe; Belisle, Elizabeth H.

    1974-01-01

    Mouse spinal cord-ganglia cultures were innoculated with murine cytomegalo-virus 14 days after explantation. Intranuclear virus was first observed 4 days after infection. The viruses, which occurred in four forms, were observed in increasing numbers during the ensuing 4 days. Differences were noted in the relative prevalence of certain of these forms in older as compared to younger cultures. This suggests that variations in virus form are related to virus maturation. Cytoplasmic viruses were occasionally observed, but their site of origin is not certain. A variety of cytoplasmic inclusions were seen, particularly in the older cultures. It seems likely that they represent specific cell responses to the presence of the virus. They were not observed in the control cultures, even though some of the latter did show severe degenerative changes. ImagesFig 1Fig 2Figs 3-4p[477]-dFig 8Fig 9Fig 10Figs 11-12Fig 13Fig 14Fig 15Fig 16Figs 17-18Fig 19 PMID:4360827

  6. Brincidofovir Use after Foscarnet Crystal Nephropathy in a Kidney Transplant Recipient with Multiresistant Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Romain Vial

    2017-01-01

    Full Text Available Background. Cytomegalovirus (CMV antiviral drug resistance constitutes an increasing challenge in transplantation. Foscarnet is usually proposed when resistance for ganciclovir is suspected, but its use is limited by its nephrotoxicity. Case Presentation. We report a case of multiresistant CMV disease in a kidney transplant recipient. Foscarnet was prescribed after ganciclovir treatment failure in a patient with two mutations in the UL97 viral gene. Foscarnet induced biopsy-proven kidney crystal precipitation that resulted in severe acute transplant failure and nephrotic syndrome. Despite a large decrease in immunosuppression, CMV disease was not controlled and a salvage therapy with Brincidofovir (BCV, which is an oral lipid conjugate of cidofovir with limited nephrotoxicity, was attempted. Clinical and virological remission was observed after a 21-day course of BCV, despite mild and reversible liver toxicity. However, a new relapse could not be effectively cured by BCV due to a new mutation in the UL54 gene, which is known to confer resistance to cidofovir. A new course of foscarnet finally resulted in prolonged CMV remission. Herein, we present a review of foscarnet nephropathy cases in solid-organ transplanted patients. Conclusions. This unique case highlights the potential benefit of BCV use during resistant CMV infection, although mutations in the UL54 gene may limit its therapeutic efficacy. These findings need to be confirmed in clinical trials.

  7. Brincidofovir Use after Foscarnet Crystal Nephropathy in a Kidney Transplant Recipient with Multiresistant Cytomegalovirus Infection

    Science.gov (United States)

    Vial, Romain; Zandotti, Christine; Alain, Sophie; Decourt, Alexandre; Purgus, Raj; Bornet, Charleric; Daniel, Laurent; Moal, Valérie

    2017-01-01

    Background. Cytomegalovirus (CMV) antiviral drug resistance constitutes an increasing challenge in transplantation. Foscarnet is usually proposed when resistance for ganciclovir is suspected, but its use is limited by its nephrotoxicity. Case Presentation. We report a case of multiresistant CMV disease in a kidney transplant recipient. Foscarnet was prescribed after ganciclovir treatment failure in a patient with two mutations in the UL97 viral gene. Foscarnet induced biopsy-proven kidney crystal precipitation that resulted in severe acute transplant failure and nephrotic syndrome. Despite a large decrease in immunosuppression, CMV disease was not controlled and a salvage therapy with Brincidofovir (BCV), which is an oral lipid conjugate of cidofovir with limited nephrotoxicity, was attempted. Clinical and virological remission was observed after a 21-day course of BCV, despite mild and reversible liver toxicity. However, a new relapse could not be effectively cured by BCV due to a new mutation in the UL54 gene, which is known to confer resistance to cidofovir. A new course of foscarnet finally resulted in prolonged CMV remission. Herein, we present a review of foscarnet nephropathy cases in solid-organ transplanted patients. Conclusions. This unique case highlights the potential benefit of BCV use during resistant CMV infection, although mutations in the UL54 gene may limit its therapeutic efficacy. These findings need to be confirmed in clinical trials. PMID:28348914

  8. 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.

  9. Cytomegalovirus infections following umbilical cord blood transplantation using reduced intensity conditioning regimens for adult patients.

    Science.gov (United States)

    Matsumura, Tomoko; Narimatsu, Hiroto; Kami, Masahiro; Yuji, Koichiro; Kusumi, Eiji; Hori, Akiko; Murashige, Naoko; Tanaka, Yuji; Masuoka, Kazuhiro; Wake, Atsushi; Miyakoshi, Shigesaburo; Kanda, Yoshinobu; Taniguchi, Shuichi

    2007-05-01

    Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation (Allo-HSCT); however, we have little information on the clinical features of CMV reactivation after cord blood transplantation using reduced-intensity regimens (RI-CBT) for adults. We reviewed medical records of 140 patients who underwent RI-CBT at Toranomon Hospital between January 2002 and March 2005. All the patients were monitored for CMV-antigenemia weekly, and, if turned positive, received preemptive foscarnet or ganciclovir. Seventy-seven patients developed positive antigenemia at a median onset of day 35 (range, 4-92) after transplant. Median of the maximal number of CMV pp65-positive cells per 50,000 cells was 22 (range, 1-1806). CMV disease developed in 22 patients on a median of day 35 (range, 15-106); 21 had enterocolitis and 1 had adrenalitis. CMV antigenemia had not been detected in 2 patients, when CMV disease was diagnosed. CMV disease was successfully treated using ganciclovir or foscarnet in 14 patients. The other 8 patients died without improvement of CMV disease. In multivariate analysis, grade II-IV acute graft-versus-host disease was a risk factor of CMV disease (relative risk 3.48, 95% confidential interval 1.47-8.23). CMV reactivation and disease develop early after RI-CBT. CMV enterocolitis may be a common complication after RI-CBT.

  10. Adjuvant and salvage therapy with leflunomide for recalcitrant cytomegalovirus infections in hematopoietic cell transplantation recipients: A case series.

    Science.gov (United States)

    El Chaer, Firas; Mori, Nobuyoshi; Shah, Dimpy; Oliver, Nora; Wang, Emily; Jan, Anna; Doan, Vi; Tverdek, Frank; Tayar, Jean; Ariza-Heredia, Ella; Chemaly, Roy F

    2016-11-01

    Cytomegalovirus (CMV) reactivation is a clinically significant complication in hematopoietic stem cell transplant (HCT) recipients. Alternative therapy for multidrug-resistant CMV is limited and often fails. Leflunomide has been used to treat resistant CMV infections, however, data on efficacy, safety, and guidance for therapeutic drug level monitoring are lacking. In this report, we describe 3 HCT recipients with multi-drug resistant CMV infections who received leflunomide as adjuvant and salvage therapy. The therapeutic effect of leflunomide as an anti-CMV agent based on virologic responses and therapeutic drug monitoring were evaluated.

  11. γδ T Cell-Mediated Immunity to Cytomegalovirus Infection

    Science.gov (United States)

    Khairallah, Camille; Déchanet-Merville, Julie; Capone, Myriam

    2017-01-01

    γδ T lymphocytes are unconventional immune cells, which have both innate- and adaptive-like features allowing them to respond to a wide spectrum of pathogens. For many years, we and others have reported on the role of these cells in the immune response to human cytomegalovirus in transplant patients, pregnant women, neonates, immunodeficient children, and healthy people. Indeed, and as described for CD8+ T cells, CMV infection leaves a specific imprint on the γδ T cell compartment: (i) driving a long-lasting expansion of oligoclonal γδ T cells in the blood of seropositive individuals, (ii) inducing their differentiation into effector/memory cells expressing a TEMRA phenotype, and (iii) enhancing their antiviral effector functions (i.e., cytotoxicity and IFNγ production). Recently, two studies using murine CMV (MCMV) have corroborated and extended these observations. In particular, they have illustrated the ability of adoptively transferred MCMV-induced γδ T cells to protect immune-deficient mice against virus-induced death. In vivo, expansion of γδ T cells is associated with the clearance of CMV infection as well as with reduced cancer occurrence or leukemia relapse risk in kidney transplant patients and allogeneic stem cell recipients, respectively. Taken together, all these studies show that γδ T cells are important immune effectors against CMV and cancer, which are life-threatening diseases affecting transplant recipients. The ability of CMV-induced γδ T cells to act independently of other immune cells opens the door to the development of novel cellular immunotherapies that could be particularly beneficial for immunocompromised transplant recipients.

  12. 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.

  13. Maternal valacyclovir and infant cytomegalovirus acquisition: a randomized controlled trial among HIV-infected women.

    Directory of Open Access Journals (Sweden)

    Alison C Roxby

    Full Text Available BACKGROUND: Studies in HIV-1-infected infants and HIV-1-exposed, uninfected infants link early cytomegalovirus (CMV acquisition with growth delay and cognitive impairment. We investigated maternal valacyclovir to delay infant acquisition of CMV. METHODS: Pregnant women with HIV-1, HSV-2 and CD4 count >250 cells/µl were randomized at 34 weeks gestation to 500 mg twice-daily valacyclovir or placebo for 12 months. Maternal CMV DNA was measured in plasma at 34 weeks gestation, in cervical secretions at 34 and 38 weeks gestation, and in breast milk at 7 postpartum timepoints; infant CMV DNA was measured in dried blood spots at 8 timepoints including birth. RESULTS: Among 148 women, 141 infants were compared in intent-to-treat analyses. Maternal and infant characteristics were similar between study arms. Infant CMV acquisition did not differ between study arms, with 46/70 infants (66% in placebo arm and 47/71 infants (66% in the valacyclovir arm acquiring CMV; median time to CMV detection did not differ. CMV DNA was detected in 92% of 542 breast milk specimens with no difference in CMV level between study arms. Change in cervical shedding of CMV DNA between baseline and 38 weeks was 0.40-log greater in the placebo arm than the valacyclovir arm (p = 0.05. CONCLUSIONS: In this cohort of HIV-1-seropositive mothers, two-thirds of infants acquired CMV by one year. Maternal valacyclovir had no effect on timing of infant CMV acquisition or breast milk CMV viral loads, although it modestly reduced cervical CMV shedding. Maternal prophylaxis to reduce infant CMV acquisition warrants further evaluation in trials with antiviral agents. TRIALS REGISTRATION: ClinicalTrials.gov NCT00530777.

  14. Use of leflunomide in a cytomegalovirus infection resistant: a report of a case

    Directory of Open Access Journals (Sweden)

    Isabel Gómez Valbuena

    2016-01-01

    Full Text Available Background and objective: cytomegalovirus (CMV infection is one of the most common complications in transplant patients, which can lead to multiple organ failure. The 80-90% of patients are cured with intravenous treatment standard (ganciclovir, or its oral prodrug (valganciclovir. In case there is no answer, we have alternatively another antiviral, foscarnet. A small number of patients do not respond to this, having a bad prognosis. The aim is to describe the case of a double lung transplant for cystic fibrosis, and recurrent CMV infection in which the use of leflunomide gets lower and even reach undetectable viral load. Description of case: woman, 22 year old, double lung transplant for cystic fibrosis in March 2014. The CMV serology performed was positive in the donor and negative in the recipient. Controls viral load during prophylaxis with valganciclovir were negative in the receiver until the 6th month after transplantation, at which viral load was detected in controls (2 090 IU/ml. The patient was admitted to our hospital to receive intravenous treatment with ganciclovir, after one month with intravenous therapy viral load persisted positive (42 400 IU/ml. One study of resistance showed that was resistant to ganciclovir, so began treatment with intravenous foscarnet. This drug achieved negativizar viral load, so the treatment was discontinued, continuing with fortnightly controls viral load. After two months without treatment, viral load increased to 13 665 IU/ml, why was requested to Pharmacy Service the off-label use of leflunomide, with the intention that use oral therapy, instead of intravenous therapy. The patient was treated with valganciclovir until have the authorization of use of leflunomide, although unanswered, since in March 2015, at the start of leflunomide treatment the patient had a viral load of 17 344 IU/ml. The initial regimen was 100 mg of leflunomide daily for the first five days, followed by 20 mg every 12 hours

  15. Vitamin D Levels After Kidney Transplantation and the Risk of Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Saber

    2015-11-01

    Full Text Available Background Some studies reported an association between low levels of vitamin D and the risk of infections, especially viral infections. Kidney transplant patients are at risk of opportunistic infections; however, no study has been conducted on the association between vitamin D levels and the risk of CMV infection. Objectives The aim of this study was to compare the level of vitamin D in two groups of patients with and without CMV infection within four months after the transplantation. Moreover, we aimed to find a relation between vitamin D level, before and after transplantation in each group. Patients and Methods; This prospective cohort study was conducted in Baqiyatallah hospital in Tehran in 2013. A total of 82 kidney transplant patients were enrolled and vitamin D levels were measured in them before transplantation. The kidney transplant patients had been followed up for four months and monitored for the presence of cytomegalovirus antigen (CMV Ag in their blood. In patients with positive CMV Ag, vitamin D level was measured again when they became positive but in other patients it was measured at the end of follow-up; at the end, characteristics of patients and vitamin D levels were compared between the two groups. Results Of all, 40 patients were CMV Ag positive and 42 patients were negative. In most patients transplanted organs were taken from cadaver (66% and the most common type of dialysis was hemodialysis (92%. Most participants did not undergo antithymocyte globulin therapy (69% and pulse corticosteroid therapy (83%. Vitamin D level before transplantation was 17.2 ± 11.6 ng/mL. In patients with positive results or at the end of follow-up in patients without CMV Ag, vitamin D level was 16.3 ± 11.4 ng/mL. Only 11% of kidney transplant patients, within four months after transplantation, had a normal level of vitamin D (> 30 ng/mL. There was no significant difference between the two groups for patients’ characteristics (P > 0

  16. 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.

  17. Prevalence, Characteristics, and One-Year Follow-Up of Congenital Cytomegalovirus Infection in Isfahan City, Iran

    Directory of Open Access Journals (Sweden)

    Pegah Karimian

    2016-01-01

    Full Text Available Introduction. Need of neonatal screening for Cytomegalovirus (CMV infection is under debate, in part because of limited data on importance of the disease regarding the prevalence of congenital CMV (cCMV infection and associated morbidity and mortality. We aimed to evaluate the prevalence and prognosis of cCMV infection in Iran, where there is high maternal seroprevalence of CMV. Methodology. This prospective study was conducted in Isfahan city, Iran, from 2014 to 2016. CMV was investigated in urine specimens by using the real-time polymerase chain reaction (RT-PCR method. CMV-infected infants were examined for clinical and laboratory findings attributed to CMV infection and followed up for one year. Results. Among 1617 studied neonates, eight (0.49% were positive for CMV infection. CMV-infected neonates were more likely to be preterm than noninfected ones (25% versus 4.5%, p=0.0508, and they had lower birth weight. Three out of the eight CMV-infected neonates had transient symptoms at birth. At follow-up, one case had mild hearing loss. Most patients had impaired growth during the one-year follow-up. Conclusions. The primary object of this study was determination of prevalence of cCMV infection in Iran as a developing country, which was at the lower range compared with other such countries. cCMV infection may result in short-term impairment in growth.

  18. Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Yutaka Hirayama; Takafumi Ando; Yoshiki Hirooka; Osamu Watanabe; Ryoji Miyahara; Masanao Nakamura; Takeshi Yamamura; Hidemi Goto

    2016-01-01

    AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus(CMV)-associated colitis in patients with active ulcerative colitis(UC).METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis.RESULTS: Multivariate analysis indicated independent associations with the extent of disease(pancolitis) anduse of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC(odds ratio = 12.672, 95%CI: 4.210-38.143).CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.

  19. Allograft rejection-related gene expression in the endothelial cells of renal transplantation recipients after cytomegalovirus infection

    Institute of Scientific and Technical Information of China (English)

    Yang LI; Jun HOU; Hang YAN; Wu-jun XUE; Pu-xun TIAN; Xiao-ming DING; Xiao-ming PAN; Xin-shun FENG; Xiao-hui TIAN; He-li XIANG

    2009-01-01

    Objective: To explore the effects of cytomegalovirus (CMV) infection on rejection-related gene expression in the endothelial cells of renal transplantation recipients. Methods: Endothelial cells (ECs) were cultured and stimulated by a variety of factors: A, normal control group; B, inactivated human cytomegalovirus (HCMV) infection group; C, HCMV infection group; D, HCMV supematant infection group; and E, ganciclovir HCMV group. Expression of intercellular adhesion molecule-1 (ICAM-1) and major histocompability complex (MHC) class Ⅰ and class Ⅱ antigens was detected by flow cytometry (FCM) and immuno-histochemistry. Results: We found characteristic CMV-infected ECs in this study. There were no significant differences among groups A, B and D (P>0.05). Although the expression levels of ICAM-1 were not significantly different between groups C and E (P>0.05), the ICAM-1 expression in these two groups was significantly higher than that in group A (P0.05). Human leucocyte antigen (HLA)-ABC expression was detected in all the groups, while HLA-DR expression was only detected in groups C and E. There were no significant dif-ferences of HLA-ABC and HLA-DR expression among groups A, B and D (P>0.05). However, the HLA-ABC and HLA-DR expression levels in groups C and D were higher than those of the remaining groups previously reported (P<0.05). Meanwhile, the HLA-ABC and HLA-DR expression levels in group E were lower than those of group C (P<0.05). Conclusion: CMV could up-regulate the expression levels of ICAM-1 and MHC antigens, which was closely related to allograft rejection.

  20. 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.

  1. Late-onset cytomegalovirus infection complicated by Guillain-Barre syndrome in a kidney transplant recipient: case report and review of the literature.

    Science.gov (United States)

    Shaban, E; Gohh, R; Knoll, B M

    2016-04-01

    Cytomegalovirus (CMV) infection remains a common infection after solid-organ transplantation. In the general population CMV disease is associated with Guillain-Barre syndrome (GBS), an autoimmune disease leading to an acute peripheral neuropathy, in 1 of 1000 cases. Interestingly, GBS is a rarely observed complication in solid-organ transplant recipients, possibly related to maintenance immunosuppression. We describe a case of CMV infection complicated by GBS in a kidney transplant recipient and review the literature.

  2. 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.

  3. 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.

  4. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  5. Activation of porcine cytomegalovirus, but not porcine lymphotropic herpesvirus, in pig-to-baboon xenotransplantation.

    Science.gov (United States)

    Mueller, Nicolas J; Livingston, Christine; Knosalla, Christoph; Barth, Rolf N; Yamamoto, Shin; Gollackner, Bernd; Dor, Frank J M F; Buhler, Leo; Sachs, David H; Yamada, Kazuhiko; Cooper, David K C; Fishman, Jay A

    2004-05-01

    Tissue-invasive disease due to porcine cytomegalovirus (PCMV) has been demonstrated after pig-to-baboon solid-organ xenotransplantation. Porcine lymphotropic herpesvirus (PLHV)-1 is associated with B cell proliferation and posttransplant lymphoproliferative disorder after allogeneic bone marrow transplantation in swine but has not been observed in pig-to-primate xenotransplantation. Activation of PCMV and PLHV-1 was investigated in 22 pig-to-baboon xenotransplants by use of quantitative polymerase chain reaction. PCMV was found in all xenografts; increased viral replication occurred in 68% of xenografts during immunosuppression. PLHV-1 was found in 12 xenografts (55%); no increases in viral replication occurred during immunosuppression. Control immunosuppressed swine coinfected with PCMV and PLHV-1 had activation of PCMV but not PLHV-1. PCMV, but not PLHV-1, is activated in solid-organ xenotransplantation.

  6. A Study on the Traditional Chinese Medicine Jinyebaidu for Prevention and Treatment of Intrauterine Infection with Guinea Pigs Cytomegalovirus

    Institute of Scientific and Technical Information of China (English)

    CHEN Suhua; XIONG Jinwen; XING Wei; WEN Liangzhen; LIU Haizhi; WANG Xinrong

    2005-01-01

    The purpose is to study the prophylactic and therapeutic effect of the traditional Chinese Medicine (TCM)-Jinyebaidu (JYBD) to guinea pig cytomegalovirus (GPCMV) intrauterine infec tion. The virus-free female and male guinea pigs were screened with nest-polymerase chain reaction (N-PCR). After inbred, pregnant guinea pigs were selected and divided into 3 groups randomly: 5guniea pigs of the blank control group were not given either GPCMV or JYBD. 31 guniea pigs of the positive control group were inoculated 1 mL (107 TCID50 ) suspension of GPCMV intraperitoneal. 10 guniea pigs of the experimental group were inoculated GPCMV firstly and then perfused stomach with JYBD for 14 days (Dosage in accordance with the modulus of the weight ratio of human to guniea pig). The effects of JYBD on the intrauterine infection of GPCMV were observed.The results showed that JYBD could decrease the maternal infection rate from 100 % (31/31) to 50% (5/10) (P<0. 001), the intrauterine infection rate from 100 % (72/72) to 75 % (21/28) (P<0. 001), and the rate of abnormal outcome of pregnancy from 64.4 % (29/45) to 25.0 % (7/28)(P<0. 001), the infective symptoms being relieved. It can be concluded that traditional Chinese medicine JYBD can prevent and treat GPCMV intrauterine infection, and can be expected a prophy lactic drug for HCMV intrauterine infection.

  7. 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.

  8. 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.

  9. 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.

  10. Successful use of oral ganciclovir for the treatment of intrauterine cytomegalovirus infection in a renal allograft recipient.

    Science.gov (United States)

    Puliyanda, D P; Silverman, N S; Lehman, D; Vo, A; Bunnapradist, S; Radha, R K; Toyoda, M; Jordan, S C

    2005-06-01

    Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns and is the leading infectious cause of congenital birth defects. Female renal allograft recipients who develop CMV infection during pregnancy are at risk for both graft dysfunction and fetal morbidity. DNA-based analysis of amniotic fluid (AF) from at-risk pregnancies has been suggested as an adjunct/substitute for traditional culture. We have shown that CMV-polymerase chain reaction of AF is a useful diagnostic test for congenital CMV infection. Using this test we diagnosed CMV infection in the fetus of a 30-year-old renal transplant recipient. As termination was not an option for the family, the patient was extensively counseled and treated with oral ganciclovir. This resulted in clearance of the virus from the AF and the delivery of a healthy newborn girl, free of CMV disease. This is the first reported case to our knowledge of successful use of maternal ganciclovir to treat intrauterine CMV infection in a pregnant renal transplant recipient.

  11. Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation

    Science.gov (United States)

    Fielding, Ceri A; Weekes, Michael P; Nobre, Luis V; Ruckova, Eva; Wilkie, Gavin S; Paulo, Joao A; Chang, Chiwen; Suárez, Nicolás M; Davies, James A; Antrobus, Robin; Stanton, Richard J; Aicheler, Rebecca J; Nichols, Hester; Vojtesek, Borek; Trowsdale, John; Davison, Andrew J; Gygi, Steven P

    2017-01-01

    The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1300 cell surface and ~7200 whole cell proteins, we demonstrate that the US12 family selectively targets plasma membrane proteins and plays key roles in regulating NK ligands, adhesion molecules and cytokine receptors. US18 and US20 work in concert to suppress cell surface expression of the critical NKp30 ligand B7-H6 thus inhibiting NK cell activation. The US12 family is therefore identified as a major new hub of immune regulation. DOI: http://dx.doi.org/10.7554/eLife.22206.001 PMID:28186488

  12. 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.

  13. Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections

    Directory of Open Access Journals (Sweden)

    Müller Marcel A

    2005-02-01

    Full Text Available Abstract Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. Cytomegalovirus iritis.

    Science.gov (United States)

    Cheng, L; Rao, N A; Keefe, K S; Avila, C P; Macdonald, J C; Freeman, W R

    1998-11-01

    We describe a case of focal cytomegalovirus iritis in a patient with acquired immunodeficiency syndrome (AIDS) who had CMV retinitis. The autopsy showed histologic evidence of focal iritis in the left eye. This iritis was characterized by infiltration of acute inflammatory cells mixed with cytomegalic cells, which was confirmed by CMV-specific immunohistochemical staining. The case suggested that cytomegalovirus could be a direct causative agent of infectious iritis in AIDS patients.

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

    Directory of Open Access Journals (Sweden)

    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. 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.

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

    Directory of Open Access Journals (Sweden)

    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. The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.

    Science.gov (United States)

    Cavignac, Yolaine; Lieber, Diana; Laib Sampaio, Kerstin; Madlung, Johannes; Lamkemeyer, Tobias; Jahn, Gerhard; Nordheim, Alfred; Sinzger, Christian

    2015-01-01

    While it is well established that human cytomegalovirus (HCMV) upregulates many cellular proteins and incorporates several of them into its virion, little is known about the functional relevance of such virus-host interactions. Two cellular proteins, Grb2 and DDX3, gained our interest as they appeared enriched in virion particles and this incorporation depended on the viral tegument protein pp65, suggesting a functional relevance. We therefore tested whether the level of these proteins is altered upon HCMV infection and whether they support viral replication. Immunoblotting analyses of cellular fractions showed increased levels of both proteins in infected cells with a maximum at 2 d p.i. and a reduction of the soluble Grb2 fraction. Knockdown of either gene by transfection of siRNAs reduced viral spread not only of the cell culture adapted HCMV strain TB40/E but also of recent clinical isolates. Apparently, Grb2 and DDX3 are proviral cellular factors that are upregulated in infected cells.

  1. The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.

    Directory of Open Access Journals (Sweden)

    Yolaine Cavignac

    Full Text Available While it is well established that human cytomegalovirus (HCMV upregulates many cellular proteins and incorporates several of them into its virion, little is known about the functional relevance of such virus-host interactions. Two cellular proteins, Grb2 and DDX3, gained our interest as they appeared enriched in virion particles and this incorporation depended on the viral tegument protein pp65, suggesting a functional relevance. We therefore tested whether the level of these proteins is altered upon HCMV infection and whether they support viral replication. Immunoblotting analyses of cellular fractions showed increased levels of both proteins in infected cells with a maximum at 2 d p.i. and a reduction of the soluble Grb2 fraction. Knockdown of either gene by transfection of siRNAs reduced viral spread not only of the cell culture adapted HCMV strain TB40/E but also of recent clinical isolates. Apparently, Grb2 and DDX3 are proviral cellular factors that are upregulated in infected cells.

  2. Oral ulceration associated with concurrent herpes simplex virus, cytomegalovirus, and Epstein-Barr virus infection in an immunocompromised patient.

    Science.gov (United States)

    Mainville, Gisele N; Marsh, William L; Allen, Carl M

    2015-06-01

    In immunocompromised patients, oral ulcerations are common and have a wide spectrum of causes, including herpesvirus infection. We report on a case in which an oral ulcer was simultaneously infected by herpes simplex (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in a kidney-pancreas transplant recipient. A 46-year-old woman presented with a clinically nonspecific dorsal tongue ulcer of 3 months duration. Histopathologic evaluation indicated keratinocytes exhibiting herpetic viral cytopathic effect. Nuclear and cytologic alterations suggestive of CMV infection were found in endothelial cells subjacent to the ulcer. Immunohistochemistry testing for HSV and CMV was positive in these cells. Large atypical mononuclear cells were also evident in the ulcer bed's inflammatory infiltrate, which had intense nuclear positivity for Epstein-Barr encoding region in situ hybridization. We believe this is the first well-documented report of the definitive concomitant presence of HSV, CMV, and EBV in an immunocompromised patient. Although the pathogenesis of coinfected ulcers remains unknown, a synergistic effect is possible.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Bassem Toema

    2011-01-01

    Hidden="false" UnhideWhenUsed="false" QFormat="true" Name="Subtle Emphasis" />

    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

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

    Directory of Open Access Journals (Sweden)

    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. 

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Primary Cytomegalovirus Infection in Seronegative Kidney Transplant Patients Is Associated with Protracted Cold Ischemic Time of Seropositive Donor Organs

    Science.gov (United States)

    Hoffmann, Dieter; Matevossian, Edouard; Lutz, Jens; Heemann, Uwe; Hösel, Volker; Busch, Dirk H.; Renders, Lutz; Neuenhahn, Michael

    2017-01-01

    Human Cytomegalovirus (CMV) can lead to primary infection or reactivation in CMV-seronegative or -seropositive kidney transplant recipients, respectively. Complications comprise severe end-organ diseases and acute or chronic transplant rejection. Risk for CMV manifestation is stratified according to the CMV-IgG-serostatus, with donor+/recipient- (D+/R-) patients carrying the highest risk for CMV-replication. However, risk factors predisposing for primary infection in CMV-seronegative recipients are still not fully elucidated. Therefore, we monitored D+/R- high-risk patients undergoing kidney transplantation in combination with antiviral prophylaxis for the incidence of CMV-viremia for a median follow-up time of 784 days (156–1155 days). In this period, we analyzed the functional CMV-specific T cell response by intracellular cytokine staining and CMV-serology by ELISA. Only four of eight D+/R- patients developed clinically relevant CMV-viremia followed by seroconversion. Viremia triggered expansion of functional CMV-specific T cells correlating with protection against secondary CMV-reactivations. In contrast, all other patients remained permanently aviremic and showed no immunological correlate of infection after discontinuation of antiviral prophylaxis for up to three years. Comparing cold ischemic times (CIT) of viremic (median = 1020 min; 720–1080 min) and aviremic patients (median = 335 min; 120–660 min) revealed significantly (p = 0.0286) protracted CIT in patients with primary CMV-infection. Taken together, primary CMV-infection affects only a subgroup of D+/R- patients correlating with length of CIT. Therefore, patients with extended CIT should be thoroughly monitored for CMV-replication well beyond discontinuation of antiviral prophylaxis. In contrast, patients with short CIT remained permanently uninfected and might benefit from shorter prophylactic treatment. PMID:28129395

  11. History of the molecular biology of cytomegaloviruses.

    Science.gov (United States)

    Stinski, Mark F

    2014-01-01

    The history of the molecular biology of cytomegaloviruses from the purification of the virus and the viral DNA to the cloning and expression of the viral genes is reviewed. A key genetic element of cytomegalovirus (the CMV promoter) contributed to our understanding of eukaryotic cell molecular biology and to the development of lifesaving therapeutic proteins. The study of the molecular biology of cytomegaloviruses also contributed to the development of antivirals to control the viral infection.

  12. Human cytomegalovirus active infection in patients with systemic lupus erythematosus: an analysis of 105 cases%系统性红斑狼疮合并人类巨细胞病毒活动性感染105例诊治分析

    Institute of Scientific and Technical Information of China (English)

    张瑾; 吴华香; 丁健; 王健; 杨婧; 张奉春; 赵岩; 曾晓峰; 张煊

    2013-01-01

    Objective To study clinical characteristics of human cytomegalovirus ( HCMV ) active infection in patients with systemic lupus erythematosus( SLE). Method All 105 cases,who were diagnosed as HCMV active infection in patients with SLE,were in-patients of the department of rheumatology of PUMC hospital from January 2006 to January 2012 and were devided into three groups based on the relationship of HCMV infection and SLE including 42 cases of HCMV triggering SLE, 31 cases of HCMV exacerbating SLE, and 32 cases of HCMV mimicking SLE flare. Their clinical manifestations, laboratory examinations and antiviral therapies were studied. Data were statistically analyzed by SPSS 17.0. Result Hematocytopenia (81% ) , fever (73. 3% ) , liver dysfunction (54. 3% ) were the most common clinical manifestations of HCMV active infection in patients with SLE, for which presence of butterfly erythema, cutaneous vasculitis, arthritis, polyserositis, central nervous system lesions and kidney lesions were clues of SLE flare. Positive rate of HCMV-pp65 was highest (84. 9% ). Afterl4-21days of inductive treatment of ganci-clovir, nine (47. 6% ) HCMV-IgM positive patients and seventeen (45. 9% ) HCMV-pp65 positive patients still remained positive, among which seven cases relapsed in three months including six (85. 7% )with continuous HCMV-pp65 antigenemia after antiviral therapy. Conclusion Clinical manifestations of HCMV active infection are similar to those of lupus flare. HCMV-pp65 is a sensitive indicator to guide antiviral therapy. Induction therapy using ganci-clovir with a duration of 14 ~21 days is not enough, and prolonged period of antiviral therapy is necessary to patients whose HCMV-pp65 remains positive.%目的 研究系统性红斑狼疮(SLE)合并人类巨细胞病毒(HCMV)活动性感染的临床特点.方法 SLE合并HCMV活动性感染的病例105例,按照HCMV感染和SLE之间的关系分为三组,即HCMV触发SLE组42例、HCMV加重SLE组31

  13. The clinical impact of cytomegalovirus infection following allogeneic hematopoietic cell transplantation: Why the quest for meaningful prophylaxis still matters.

    Science.gov (United States)

    Chan, Shawna T; Logan, Aaron C

    2017-02-02

    Latent infection with human cytomegalovirus (CMV) is common. Functional immunity effectively contains such latent infections; however, CMV reactivation may cause significant complications in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). In spite of the universal implementation of post-transplant screening for CMV viremia and the institution of pre-emptive antiviral management, CMV disease still occurs in a small portion of patients. Moreover, interactions between CMV and the immune system have significant implications for the incidence of graft-versus-host disease, the recurrence of malignancy, and non-relapse mortality following alloHCT, even in the era of pre-emptive antiviral management. CMV serostatus thus remains an important consideration for patients undergoing alloHCT. We review the clinical impact of CMV in the setting of alloHCT, interactions between CMV serostatus, viral reactivation, and transplant outcomes, as well as current and evolving strategies for prevention and treatment of CMV-related complications that may have significant impact for alloHCT recipients.

  14. Clinical features of late cytomegalovirus infection after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Asano-Mori, Yuki; Kanda, Yoshinobu; Oshima, Kumi; Kako, Shinichi; Shinohara, Akihito; Nakasone, Hideki; Sato, Hiroyuki; Watanabe, Takuro; Hosoya, Noriko; Izutsu, Koji; Asai, Takashi; Hangaishi, Akira; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2008-04-01

    Late cytomegalovirus (CMV) disease beyond day 100 after hematopoietic stem cell transplantation (HSCT) has become an increasing problem after the introduction of preemptive ganciclovir (GCV) administration. To clarify the risk factors and outcome for late CMV reactivation and disease, we retrospectively analyzed the records of 101 Japanese adult patients who underwent allogeneic HSCT between 1998 and 2005 at our hospital. Fifty-one developed late positive CMV antigenemia, with a cumulative incidence of 53%. Recipient CMV seropositivity, the use of alemtuzumab, chronic GVHD, and high-dose steroids were significantly associated with late positive antigenemia. Eight patients developed late CMV disease, with a cumulative incidence of 8%, including retinitis and gastrointestinal disease. None progressed to a fatal disease. The use of alemtuzumab was identified as an independent significant risk factor for late CMV disease, although it was not associated with increased non-relapse mortality. Among the 51 patients with late positive antigenemia, 28 had consistently less than three positive cells, 25 of whom showed negative conversion without antiviral agents. In conclusion, late CMV antigenemia appeared to develop frequently, especially in patients with profound immune suppression; however, a fatal outcome could be prevented by optimal preemptive therapy. Low-level antigenemia may not require antiviral treatments.

  15. 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.

  16. 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.

  17. Reduced dose of foscarnet as preemptive therapy for cytomegalovirus infection following reduced-intensity cord blood transplantation.

    Science.gov (United States)

    Narimatsu, H; Kami, M; Kato, D; Matsumura, T; Murashige, N; Kusumi, E; Yuji, K; Hori, A; Shibata, T; Masuoka, K; Wake, A; Miyakoshi, S; Morinaga, S; Taniguchi, S

    2007-03-01

    Although foscarnet is a promising alternative for the treatment of cytomegalovirus (CMV) infection, its toxicity can be significant in patients with advanced age. We retrospectively reviewed medical records of 123 patients (median age of 55; range, 17-79) who received reduced-intensity cord blood transplantation (RI-CBT). Patients preemptively received reduced-dose foscarnet 30 mg/kg twice daily when CMV antigenemia exceeded 10/50,000. Sixty-three patients developed CMV antigenemia on a median of day 34, and 29 received foscarnet preemptively. The median level of CMV antigenemia at the initiation of foscarnet was 30. Median duration of foscarnet administration was 24 days. Adverse effects included electrolyte abnormalities (n=19), renal impairment (n=13), and skin eruption requiring discontinuation of foscarnet (n=1). Preemptive therapy of foscarnet was completed in 18 patients. Seven patients died during foscarnet use without developing CMV disease. The remaining 3 developed CMV enterocolitis 5, 14, and 17 days after initiation of foscarnet. All of them were successfully treated with ganciclovir or foscarnet. Reduced dose of foscarnet is beneficial to control CMV reactivation following RI-CBT; however, it has considerable toxicities in RI-CBT recipients with advanced age. Further studies are warranted to minimize toxicities and identify optimal dosages.

  18. Colonic perforation in a patient with systemic lupus erythematosus accompanied by cytomegalovirus infection: A case report

    Directory of Open Access Journals (Sweden)

    Yuichi Tachikawa

    2016-01-01

    Conclusion: Our case underscores the importance of exploring the possibility of CMV infection as a differential diagnosis in SLE patients with obvious gastrointestinal symptoms who were treated by immunosuppressive drugs.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    Fornara, O; Bartek, J; Rahbar, A;

    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......-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...

  2. Dual-color bioluminescent assay using infected HepG2 cells sheds new light on Chlamydia pneumoniae and human cytomegalovirus effects on human cholesterol 7α-hydroxylase (CYP7A1) transcription.

    Science.gov (United States)

    Michelini, Elisa; Donati, Manuela; Aldini, Rita; Cevenini, Luca; Mezzanotte, Laura; Nardini, Paola; Foschi, Claudio; Zvi, Ido Ben; Cevenini, Monica; Montagnani, Marco; Marangoni, Antonella; Roda, Aldo; Cevenini, Roberto

    2012-11-01

    Chlamydia pneumoniae and human cytomegalovirus (HCMV) are intracellular pathogens able to infect hepatocytes, causing an increase in serum triglycerides and cholesterol levels due to the production of inflammatory cytokines. We investigated whether these pathogens could interfere with cholesterol metabolism by affecting activity of hepatic cholesterol 7α-hydroxylase (CYP7A1) promoter. CYP7A1 is the rate-limiting enzyme responsible for conversion of cholesterol to bile acids, which represents the main route of cholesterol catabolism. A straightforward dual-reporter bioluminescent assay was developed to simultaneously monitor CYP7A1 transcriptional regulation and cell viability in infected human hepatoblastoma HepG2 cells. C. pneumoniae and HCMV infection significantly decreased CYP7A1 promoter activity in a dose-dependent manner, with maximal inhibitions of 33±10% and 32±4%, respectively, at a multiplicity of infection of 1. To support in vitro experiments, serum cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and glucose levels were also measured in Balb/c mice infected with C. pneumoniae. Serum cholesterol and triglycerides also increased in infected mice compared with controls. Although further investigation is required, this work presents the first experimental evidence that C. pneumoniae and HCMV inhibit CYP7A1 gene transcription in the cultured human hepatoblastoma cell line.

  3. Acute cervicitis and vulvovaginitis may be associated with Cytomegalovirus

    OpenAIRE

    Abou, Magali; Dällenbach, Patrick

    2013-01-01

    Cytomegalovirus (CMV) infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosic syndrome. Its association with acute cervicitis and vulvovaginitis has rarely been reported.

  4. 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

  5. Prevalence of cytomegalovirus infection in different patient groups of a urban university in Brazil

    Directory of Open Access Journals (Sweden)

    José Hermôgenes Rocco Suassuna

    1995-06-01

    Full Text Available This study sought for etndence of previous CMV infection in patients of a general hospital serving the low income population of Rio de Janeiro. An enzyme immunoassay was used to detect anti-CMV antibodies in 713 typical hospital patients classified into eight different groups. Positive tests were found in 87% of pregnant women, 85% of newborns, 61% of pediatric patients, 77% of adolescent patients, 81% of adult patients, 87% of dialysed transplant candidates, 89% of kidney donors, and 92% of patients after transplantation. Depending of the subgroup studied these results carry different meanings and necessitate different clinical approaches. The risk of congenital disease is probably low in view of the reduced number of pregnant women still susceptible to primary infection. The number of primary infections will also be low in transplant recipients. However, those still susceptible will almost certainly acquire the infection from, their donor. Prophylactic CMV matching in kidney transplantation is not a realistic approach due to the low probability of finding pairs of seronegative donors and recipients.

  6. Clinical manifestations of human cytomegalovirus (HCMV) infection in children in the first few months of life

    OpenAIRE

    Aziza Khodjaeva

    2012-01-01

    The research objective was to study frequency of antenatal infection and record probable clinical manifestations in 100 children with HCMV born from mother with HCMV in blood and mononuclear cells. The study identified poly-systemic internal organ damage in neonates due to prenatal HCMV. Research procedures involved study of 100 pairs of patients, Mother-Child tandem, using regular clinical assessment methods per algorithm and HCMV diagnostic methods: ELISA, affinity and avidity of HCMV antib...

  7. 巨细胞病毒感染免疫逃避机制研究进展%Progress in immune evasion mechanisms of cytomegalovirus infection

    Institute of Scientific and Technical Information of China (English)

    刘逦玮

    2014-01-01

    巨细胞病毒人群感染率较高.初次感染后,巨细胞病毒通过其独特的免疫逃避机制抑制宿主固有及获得性免疫应答,使机体无法完全清除病毒而形成潜伏感染.然而,其感染的免疫逃避机制仍未明确.近年来研究发现,巨细胞病毒可通过阻止感染细胞表面病毒抗原的表达来影响T细胞的识别,以及调节NK细胞表面抑制性/活化性受体-配体之间的平衡来抑制自然杀伤细胞的杀伤作用等多种途径逃避机体的抗病毒反应,达到免疫抑制的目的.该文阐述巨细胞病毒感染后逃避宿主免疫系统攻击的机制,并展望免疫治疗前景,为进一步展开免疫逃避机制的研究提供参考.%Human cytomegalovirus (HCMV) is a highly prevalent infection and it has become a paradigm for viral immune evasion due to its unique multitude of immune-modulatory strategies on host innate and adaptive immune response.Following primary infection,CMV can persist as a subclinical,recurrent infection for the lifetime of an individual because human immune system is unable to clarify.However,the immune evasion mechanism of CMV remains unclear.Recent data has revealed an astounding variety of methods in immune evasion to suppress host immune system,including inhibiting antigen presentation on infected cell surfaces to protect against T cell recognition and regulating the balance between natural killer cell inhibitory/activating receptor and ligand pairs to avoid NK cell attack.This review summarizes the latest literature regarding how CMV encodes a multitude of immune modulatory mechanisms devoted to escaping the host antiviral response,presents the future perspective of immunotherapy,and provides references for in-depth understanding of the immune evasion mechanisms leading to the control of CMV.

  8. The Effects of Allitridin on the Expression of Transcription Factor T-bet/GATA-3 in Mice Infected by Murine Cytomegalovirus

    Institute of Scientific and Technical Information of China (English)

    徐翼; 方峰; 甄宏; 向稚丹; 李革

    2004-01-01

    The aim of this study is to investigate the effects of allitridin on the expression of transcription factor T-bet/GA-TA-3 in mice infected by murine cytomegalovirus. BALB/c mice model system of murine cytomegalovirus (MCMV) infection was established. In which 20 model mice were allocated randomly into allitridin treated group ( n = 10) and infected control group (n=10). Allitridin (25mg·kg-1·d-1 ) was used in treated group at the 24 h by intraperitoneal route (once/d× 14d), and the same volume of saline solution was injected control mice. Normal control mice (n = 10), were only given with the same volume of 0.89% sodium chloride, without infection with MCMV. The expression levels of transcription factor T-bet/GATA-3 mRNA were measured by RT-PCR, and the expression levels of T helper 1 (Thl) cytokine IFN-γ and Th2 cytokine IL-10 in supernatant of spleen cell culture were measured by ELISA. Experimental results showed MCMV infection could markedly down-modulate the expression of IFN-γ and T-bet, and significantly up-modulate the expression of IL-10 and GATA-3 mRNA. Allitridin could induce increased expression of transcription factor T-bet mRNA and Thl cytokine IFN-γ significantly ( P < 0.01 ), and decreased expression of transcription factor GATA-3 mRNA and Th2 cytokine IL-10 markedly (P<0.01). It is concluded that MCMV infection leads to disequilibrium of Thl/Th2 cytokine expression: the level of Thlcytokine IFN-γ decreases significantly and Th2 cytokine IL-10 overexpresses markedly. Allitridin can up-regulate the expression of T-bet and IFN-γ, and inhibit the expression of GATA-3 mRNA and IL-10 in MCMV infected mice, indicating a Th1 dominant state which should enhance the specific cellular immune reactions against CMV and be helpful for clearance of the cytomegalovirus in host.

  9. 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".

  10. 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.

  11. Prevalence of cytomegalovirus infection in different patient groups of a urban university in Brazil

    Directory of Open Access Journals (Sweden)

    José Hermôgenes Rocco Suassuna

    1995-06-01

    Full Text Available This study sought for etndence of previous CMV infection in patients of a general hospital serving the low income population of Rio de Janeiro. An enzyme immunoassay was used to detect anti-CMV antibodies in 713 typical hospital patients classified into eight different groups. Positive tests were found in 87% of pregnant women, 85% of newborns, 61% of pediatric patients, 77% of adolescent patients, 81% of adult patients, 87% of dialysed transplant candidates, 89% of kidney donors, and 92% of patients after transplantation. Depending of the subgroup studied these results carry different meanings and necessitate different clinical approaches. The risk of congenital disease is probably low in view of the reduced number of pregnant women still susceptible to primary infection. The number of primary infections will also be low in transplant recipients. However, those still susceptible will almost certainly acquire the infection from, their donor. Prophylactic CMV matching in kidney transplantation is not a realistic approach due to the low probability of finding pairs of seronegative donors and recipients.Evidência de infecção passada por citomegalovírus foi pesquisada em pacientes de um hospital que serve à população de baixa renda na cidade do Rio de faneiro. Realizou-se, com um imunoensaio enzimãtico, a pesquisa de anticoipos anti-CMV em 713 pacientes hospitalares, divididos em oito grupos. As taxas observadas foram 87% para grávidas, 85% para recém-natos, 61% para pacientes pediátricos, 77% para adolescentes e 81% para adultos, 87% para pacientes em diálise, 89% para doadores de rim e 92% para pacientes após o transplante renal. Estes resultados têm diferentes significados e implicam em diferentes abordagens clínicas dependendo do subgrupo estudado. O risco de infecção congênita provavelmente é baixo devido ao reduzido número de mulheres grávidas ainda susceptíveis a infecções primárias. Pelo mesmo motivo, o número de

  12. Clinical manifestations of human cytomegalovirus (HCMV infection in children in the first few months of life

    Directory of Open Access Journals (Sweden)

    Aziza Khodjaeva

    2012-10-01

    Full Text Available The research objective was to study frequency of antenatal infection and record probable clinical manifestations in 100 children with HCMV born from mother with HCMV in blood and mononuclear cells. The study identified poly-systemic internal organ damage in neonates due to prenatal HCMV. Research procedures involved study of 100 pairs of patients, Mother-Child tandem, using regular clinical assessment methods per algorithm and HCMV diagnostic methods: ELISA, affinity and avidity of HCMV antibodies, and HCMV genome identification via PCR method in blood plasma and mononuclear cells. Initial clinical disease manifested in 71% of children during late neonatal period. Children who died of HCMV (5% were infected antenatal, and 39% were born prematurely. Embryonic stigma found in five cases. HCMV’s affinity to different tissues during the process of embryogenesis leads of poly-systemic damage and results in various clinical manifestations in the postnatal period. HCMV’s ability to invade mononuclear blood cells jeopardizes the antivirus defense system. The research is vital to deter the transmission of the virus and provide HCMV specific treatment to couples planning to have children.

  13. 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.

  14. 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.

  15. 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.

  16. Cytomegalovirus (CMV) IE1- and pp65-specific CD8+ T cell responses broaden over time after primary CMV infection in infants.

    Science.gov (United States)

    Gibson, Laura; Dooley, Sheryl; Trzmielina, Sonia; Somasundaran, Mohan; Fisher, Donna; Revello, Maria Grazia; Luzuriaga, Katherine

    2007-06-15

    Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality in young children. We have previously shown that CD8+ T cell responses to CMV pp65 or IE1 protein were readily detectable in children with congenital or postnatal CMV infection. Here, we have further characterized the evolution of the peptide specificity of these responses in 7 infants<6 months of age at the start of the study. Thirteen pp65 and 15 IE1 peptides (median, 5 peptides/infant) were targeted, and most (61%) represented sequences not previously reported. Peptide specificity remained stable or broadened over time despite the clearance of CMV viremia. Loss of peptide recognition was not observed. Responses with the highest functional peptide avidity were not necessarily detected earliest. These data provide additional evidence that young infants can generate diverse CMV-specific CD8+ T cell responses but show that early responses may exhibit relatively focused peptide specificity and lower peptide avidity.

  17. Human cytomegalovirus and mucoepidermoid carcinoma of salivary glands: cell-specific localization of active viral and oncogenic signaling proteins is confirmatory of a causal relationship.

    Science.gov (United States)

    Melnick, Michael; Sedghizadeh, Parish P; Allen, Carl M; Jaskoll, Tina

    2012-02-01

    Human cytomegalovirus (hCMV) infection is common. Although still controversial, there is growing evidence that active hCMV infection is associated with a variety of malignancies, including brain, breast, lung, colon, and prostate. Given that hCMV is frequently resident in salivary gland (SG) ductal epithelium, we hypothesized that hCMV would be important to the pathogenesis of SG mucoepidermoid carcinoma (MEC). This was initially supported by our finding that purified CMV induces malignant transformation in SG cells in an in vitro mouse model, and utilizes a pathogenic pathway previously reported for human MEC. Here we present the histologic and molecular characterizations of 39 human SG MECs selected randomly from a repository of cases spanning 2004-2011. Serial sections were obtained from formalin-fixed, paraffin embedded, tissue blocks from previous incisional or excisional biopsies. Immunohistochemical assays were performed for active hCMV proteins (IE1 and pp65) and the activated COX/AREG/EGFR/ERK signaling pathway. All four prospective causal criteria for viruses and cancer are fully satisfied: (1) protein markers for active hCMV are present in 97% of MECs; (2) markers of active hCMV are absent in non-neoplastic SG tissues; (3) hCMV-specific proteins (IE1, pp65) are in specific cell types and expression is positively correlated with severity; (4) hCMV correlates and colocalizes with an upregulation and activation of an established oncogenic signaling pathway (COX/AREG/EGFR/ERK). Thus, the evidential support reported here and previously in a mouse model is strongly confirmatory of a causal relationship between hCMV and SG mucoepidermoid carcinoma. To our knowledge, this is the first demonstration of hCMV's role in human oncogenesis that fully responds to all of Koch's Postulates as revised for viruses and cancer. In the absence of any contrary evidence, hCMV can reasonably be designated an "oncovirus."

  18. Proteomic analyses of human cytomegalovirus strain AD169 derivatives reveal highly conserved patterns of viral and cellular proteins in infected fibroblasts.

    Science.gov (United States)

    Reyda, Sabine; Büscher, Nicole; Tenzer, Stefan; Plachter, Bodo

    2014-01-07

    Human cytomegalovirus (HCMV) particle morphogenesis in infected cells is an orchestrated process that eventually results in the release of enveloped virions. Proteomic analysis has been employed to reveal the complexity in the protein composition of these extracellular particles. Only limited information is however available regarding the proteome of infected cells preceding the release of HCMV virions. We used quantitative mass spectrometry to address the pattern of viral and cellular proteins in cells, infected with derivatives of the AD169 laboratory strain. Our analyses revealed a remarkable conservation in the patterns of viral and of abundant cellular proteins in cells, infected for 2 hours, 2 days, or 4 days. Most viral proteins increased in abundance as the infection progressed over time. Of the proteins that were reliably detectable by mass spectrometry, only IE1 (pUL123), pTRS1, and pIRS1 were downregulated at 4 days after infection. In addition, little variation of viral proteins in the virions of the different viruses was detectable, independent of the expression of the major tegument protein pp65. Taken together these data suggest that there is little variation in the expression program of viral and cellular proteins in cells infected with related HCMVs, resulting in a conserved pattern of viral proteins ultimately associated with extracellular virions.

  19. 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.

  20. Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation

    NARCIS (Netherlands)

    Hertoghs, K.M.L.; Moerland, P.D.; van Stijn, A.; Remmerswaal, E.B.M.; Yong, S.L.; van de Berg, P.J.E.J.; Ham, S.M.; Baas, F.; ten Berge, R.J.M.; van Lier, R.A.W.

    2010-01-01

    CD8+ T cells play a critical role in the immune response to viral pathogens. Persistent human cytomegalovirus (HCMV) infection results in a strong increase in the number of virus-specific, quiescent effector-type CD8+ T cells with constitutive cytolytic activity, but the molecular pathways involved

  1. 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.

  2. 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.

  3. Cytomegalovirus pp71 protein is expressed in human glioblastoma and promotes pro-angiogenic signaling by activation of stem cell factor.

    Directory of Open Access Journals (Sweden)

    Lisa A Matlaf

    Full Text Available Glioblastoma multiforme (GBM is a highly malignant primary central nervous system neoplasm characterized by tumor cell invasion, robust angiogenesis, and a mean survival of 15 months. Human cytomegalovirus (HCMV infection is present in >90% of GBMs, although the role the virus plays in GBM pathogenesis is unclear. We report here that HCMV pp71, a viral protein previously shown to promote cell cycle progression, is present in a majority of human GBMs and is preferentially expressed in the CD133+, cancer stem-like cell population. Overexpression of pp71 in adult neural precursor cells resulted in potent induction of stem cell factor (SCF, an important pro-angiogenic factor in GBM. Using double immunofluorescence, we demonstrate in situ co-localization of pp71 and SCF in clinical GBM specimens. pp71 overexpression in both normal and transformed glial cells increased SCF secretion and this effect was specific, since siRNA mediated knockdown of pp71 or treatment with the antiviral drug cidofovir resulted in decreased expression and secretion of SCF by HCMV-infected cells. pp71- induced upregulation of SCF resulted in downstream activation of its putative endothelial cell receptor, c-kit, and angiogenesis as measured by increased capillary tube formation in vitro. We demonstrate that pp71 induces a pro-inflammatory response via activation of NFΚB signaling which drives SCF expression. Furthermore, we show that pp71 levels and NFKB activation are selectively augmented in the mesenchymal subtype of human GBMs, characterized by worst patient outcome, suggesting that HCMV pp71-induced paracrine signaling may contribute to the aggressive phenotype of this human malignancy.

  4. 妊娠期巨细胞病毒感染诊断研究进展%Update on Diagnosis of Cytomegalovirus Infection During Pregnancy

    Institute of Scientific and Technical Information of China (English)

    沈凤贤

    2013-01-01

    Human cytomegalovirus (CMV) is the most common pathogene of congenital viral infection. Pathological changes of placenta resulted from CMV infection of placenta combined with cytopathy caused by fetal infection induce serious birth defects, which will be severe challenges to aristogenesis rearing of the state. For a long time, scholars in different countries have been working together to prevent and control symptomatic congenital CMV infection. Both primary and secondary maternal infection can cause intrauterine transmission. CMV serological screening is important for identifying high risk pregnancy. HCMV-specific IgG avidity assay provides more information besides IgG and IgM testing. Once we prove maternal CMV infection, fetal prognosis assessment is most critical. Amniotic fluid CMV-DNA detection and imaging studies could be used to diagnosis of intrauterine infection and fetal prognosis.%人巨细胞病毒(cytomegalovirus,CMV)是最常见的先天感染病毒.胎盘细胞感染CMV致胎盘病理改变和胎儿感染CMV导致严重的出生缺陷,对优生优育是严峻的挑战,长期以来各国学者一直致力于先天性CMV感染及其出生缺陷的防治研究.妊娠妇女的原发感染或者继发感染均可引起先天性CMV感染,妊娠前或者妊娠期CMV血清学筛查对于发现高危妊娠妇女非常重要,IgG抗体亲和力测定方法为现有IgG和IgM检测提供了很好的信息补充.一旦确诊妊娠妇女感染CMV,胎儿预后的评估非常重要,羊水CMV检测和影像学检查一方面可以用于宫内感染的诊断,另一方面也可以提供一定的胎儿预后信息.

  5. Congenital cytomegalovirus infection in severe fetal malformations%巨细胞病毒宫内感染与胎儿严重畸形的相关性

    Institute of Scientific and Technical Information of China (English)

    林晓倩; 王景美; 刘景丽; 王志群; 戴毅敏; 李洁; 朱湘玉; 茹彤; 周乙华

    2015-01-01

    45) years, t=-1.792], weight [(51.3±6.7) vs (55.0±8.0) kg, t=-1.204], and the proportion of education background lower than junior high school [3/7 vs 30.0% (129/429), Fisher's exact test], previous adverse pregnancy outcomes [0/7 vs 6.8% (29/429), Fisher's exact test], vaginal bleeding in early pregnancy [1/7 vs 22.8%(98/429), Fisher's exact test], and male fetuses [4/7 vs 54.3% (233/429), Fisher's exact test], all P > 0.05.There were respectively six and 151 fetuses in CMV-infected and non CMV-infected group receiving chromosome analysis.However, the incidence of chromosomal abnormalities was not significantly different between the two groups [0/6 vs 30.5% (46/151)] (Fisher's exact test, P=0.181).Of the 293 women with serum samples available, 285 (97.3%) were CMV IgG positive, and six (2.0%) were also CMV IgM positive (active infection).Conclusions There is no strong association between CMV infection and severe fetal malformations in Nanjing and the surrounding areas, which indicates that routine prenatal screening for CMV has limited value to evaluate severe fetal malformations.%目的 探讨巨细胞病毒(cytomegalovirus,CMV)宫内感染与胎儿严重畸形的相关性. 方法 2007年1 2月至2014年12月,在南京大学医学院附属鼓楼医院就诊的南京及周边地区孕妇中,经产前B超和/或MRI发现胎儿严重畸形而终止妊娠者共436例.留取孕妇外周血和脐血,采用酶联免疫吸附试验检测血清CMV IgM和IgG抗体.引产后行病理解剖,取胎肾、肺、肝、皮肤、心脏和胎盘组织以及脐血白细胞、脐血血浆和羊水沉淀悬液,采用荧光定量聚合酶链反应技术检测CMV DNA.胎肾CMV DNA阳性和/或脐血CMV IgM阳性诊断CMV宫内感染.采用独立样本t检验、x2检验或Fisher精确概率法进行统计学分析. 结果 436例胎儿中,7例(1.6%)胎肾CMV DNA阳性,且肺、肝、皮肤、心脏和胎盘以及脐血、羊水等组织或

  6. 21 CFR 866.3175 - Cytomegalovirus serological reagents.

    Science.gov (United States)

    2010-04-01

    ... cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal... (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection...

  7. Evaluation of different cytomegalovirus (CMV) DNA PCR protocols for analysis of dried blood spots from consecutive cases of neonates with congenital CMV infections.

    Science.gov (United States)

    Soetens, Oriane; Vauloup-Fellous, Christelle; Foulon, Ina; Dubreuil, Pascal; De Saeger, Ben; Grangeot-Keros, Liliane; Naessens, Anne

    2008-03-01

    Two protocols for the extraction of cytomegalovirus (CMV) DNA and two methods for the amplification of CMV DNA in dried blood spots were evaluated for the retrospective diagnosis of congenital CMV infection. During the period from 1996 to 2006, a urine screening program detected 76 congenitally infected neonates. Stored Guthrie cards with blood from 55 cases and 12 controls were tested. Two spots of dried blood were cut from each card and evaluated in two centers. CMV DNA was extracted from a whole single spot. Center 1 used phenol-chloroform extraction and ethanol precipitation followed by a conventional PCR. Center 2 used the NucliSens easyMAG automated DNA/RNA extraction platform (bioMérieux) followed by a real-time PCR. For evaluation of the extraction method, DNA extracted from each blood spot was evaluated by the amplification method used by the collaborating center. The sensitivities were 66% for center 1 and 73% for center 2. None of the controls were positive. A sensitivity as high as 82% could be obtained by combining the most sensitive extraction method (the phenol-chloroform procedure) with the most sensitive PCR method (real-time PCR). The detection rate was not influenced by the duration of storage of the spots. The sensitivity was higher with blood from congenitally infected cases due to a primary maternal CMV infection, regardless of the protocol used. However, the difference reached significance only for the least-sensitive protocol (P = 0.036).

  8. 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.

  9. Epigenetic Control of Cytomegalovirus Latency and Reactivation

    Directory of Open Access Journals (Sweden)

    Mary Hummel

    2013-05-01

    Full Text Available Cytomegalovirus (CMV gene expression is repressed in latency due to heterochromatinization of viral genomes. In murine CMV (MCMV latently infected mice, viral genomes are bound to histones with heterochromatic modifications, to enzymes that mediate these modifications, and to adaptor proteins that may recruit co-repressor complexes. Kinetic analyses of repressor binding show that these repressors are recruited at the earliest time of infection, suggesting that latency may be the default state. Kidney transplantation leads to epigenetic reprogramming of latent viral chromatin and reactivation of immediate early gene expression. Inflammatory signaling pathways, which activate transcription factors that regulate the major immediate early promoter (MIEP, likely mediate the switch in viral chromatin.

  10. Foscarnet-Resistant Cytomegalovirus Esophagitis with Stricturing

    Directory of Open Access Journals (Sweden)

    Vinaya Gaduputi

    2013-01-01

    Full Text Available We report the case of a 52-year-old man with HIV-AIDS, non-complaint with highly active antiretroviral therapy, who presented with long-standing dysphagia. He was treated for three episodes of severe Candida esophagitis with fluconazole and later caspofungin due to poor response. In spite of the prolonged treatment courses the patient did not report an improvement in his symptoms. He was also concomitantly being treated for other opportunistic infections including cytomegalovirus (CMV retinitis with i.v. foscarnet for almost 2 months prior to the index presentation. Upper esophagogastroduodenoscopy revealed multiple superficial ulcers with stricturing. Bougie dilatation was attempted but failed. The biopsy specimens revealed multiple intracellular inclusion bodies pathognomonic of CMV infection. We aim to highlight the increasing resistance of CMV to conventional first-line antiviral agents such as foscarnet.

  11. 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.

  12. Properties of virion transactivator proteins encoded by primate cytomegaloviruses

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  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. 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.

  16. Improving Safety of Preemptive Therapy with Oral Valganciclovir for Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Corinna Barkam

    2012-01-01

    Full Text Available Valganciclovir (VGC, an oral prodrug of ganciclovir (GCV, has been shown to clear cytomegalovirus (CMV viremia in preemptive treatment of patients after allogeneic hematopoietic stem cell transplantation (alloHSCT, apparently without significant toxicity. Since VGC obviates hospitalization, it is increasingly being adopted, although not approved, in alloHSCT. When we retrospectively evaluated preemptive treatment with VGC versus GCV, foscarnet or cidofovir, in all 312 consecutive CMV viremias of 169 patients allotransplanted at our institution between 1996 and 2006, we found VGC more efficacious (79% than non-VGC therapies (69%. The advantage of outpatient VGC, however, was outbalanced by more profound neutropenias (including two cases of agranulocytosis, one with graft loss requiring subsequent prolonged rehospitalization. Thus, in a second, prospective cohort from 2007 to 2011 (all 202 consecutive CMV viremias of 118 yet older and sicker patients, we implemented twice weekly neutrophil monitoring during outpatient VGC treatment and avoided VGC maintenance therapy. While conserving efficacy (VGC 71%, non-VGC 72%, we could now demonstrate a reduced mean duration of hospitalization with VGC (9 days (0–66 compared to non-VGC (25 days (0–115, without any agranulocytosis episodes. We conclude that safe outpatient VGC therapy is possible in alloHSCT recipients, but requires frequent monitoring to prevent severe myelotoxicity.

  17. 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

  18. Specific remodeling of splenic architecture by cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Chris A Benedict

    2006-03-01

    Full Text Available Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21. The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  19. Specific remodeling of splenic architecture by cytomegalovirus.

    Science.gov (United States)

    Benedict, Chris A; De Trez, Carl; Schneider, Kirsten; Ha, Sukwon; Patterson, Ginelle; Ware, Carl F

    2006-03-01

    Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV) infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC) as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21). The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT)-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  20. Effect of Mycoplasma hominis and cytomegalovirus infection on pregnancy outcome: A prospective study of 200 Mongolian women and their newborns

    Science.gov (United States)

    Batbaatar, Gunchin; Tsogtsaikhan, Sandag; Enkhtsetseg, Jamsranjav; Enkhjargal, Altangerel; Pfeffer, Klaus; Adams, Ortwin; Battogtokh, Chimeddorj

    2017-01-01

    In Mongolia, diagnostic tests for the detection of the sexually transmitted mycoplasmas, ureaplasmas, Herpes simplex virus (HSV), and cytomegalovirus (CMV) are currently not routinely used in clinical settings and the frequency of these STIs are enigmatic. The prevalence of these STI pathogens were prospectively evaluated among 200 Mongolian pregnant women and their newborns and correlated with pregnancy outcome. TaqMan PCRs were used to detect bacterial and viral STI pathogens in pre-birth vaginal swabs of the pregnant women and in oral swabs of their newborns. A standardized questionnaire concerning former and present pregnancies was developed and linear regression analysis was used to correlate pathogen detection with pregnancy outcome. Ureaplasmas were the most prevalent of the tested pathogens (positive in 90.5% positive women and 47.5% newborns), followed by mycoplasmas (32.5% and 7.5%), chlamydia (14.5% and 7.5%), trichomonas (8.5% and 4.0%) and gonococcus (0.5% and 0%). CMV was found in 46.5% of the pregnant women and in 10.5% of their newborns, whereas HSV-2 was detected in only two mothers. Multiple regression analyses indicate that colonization of the mothers with U. urealyticum, M. hominis, T. vaginalis or CMV is associated with transmission to newborns and that transmission of M. hominis or CMV from Mongolian pregnant women to offspring is associated with reduced neonatal length and gestational age. Thus, diagnostic tests for their detection should be implemented in the clinical settings in Mongolia. PMID:28257513

  1. EPSTEIN-BARR VIRUS AND CYTOMEGALOVIRUS – TWO HERPES VIRUSES WITH ORAL MANIFESTATIONS.

    Directory of Open Access Journals (Sweden)

    Assya Krasteva

    2013-09-01

    Full Text Available Diseases caused by cytomegalovirus and Epstein-Barr virus are reported with increasing frequency. Epstein-Barr virus damages usually are due to reactivation of latent infection. while cytomegalovirus disease result from primary or reactivated infection in susceptible hosts. The booth infections can have oral manifestations.

  2. 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

  3. Detection of human cytomegalovirus pp67 late gene transcripts in cerebrospinal fluid of human immunodeficiency virus type 1-infected patients by nucleic acid sequence-based amplification.

    Science.gov (United States)

    Zhang, F; Tetali, S; Wang, X P; Kaplan, M H; Cromme, F V; Ginocchio, C C

    2000-05-01

    This study examined the clinical correlation between the presence of human cytomegalovirus (HCMV) pp67 mRNA in cerebrospinal fluid (CSF) and active HCMV central nervous system (CNS) disease in patients with human immunodeficiency virus type 1 (HIV-1). In total, 76 CSF specimens collected from 65 HIV-1-positive patients diagnosed with HCMV CNS disease, other non-HCMV-related CNS diseases, or no CNS disease were tested for the presence of HCMV pp67 mRNA using the NucliSens cytomegalovirus (CMV) pp67 assay (Organon Teknika, Durham, N.C.). The results were compared to those of a nested PCR for the detection of HCMV glycoprotein B DNA and to those obtained by viral culture (54 samples). CSF specimens collected from patients without HCMV CNS disease yielded the following results: pp67 assay negative, 62 of 62 specimens; culture negative, 41 of 41 specimens; and PCR negative, 56 of 62 specimens (6 specimens were positive). CSF specimens collected from patients with HCMV CNS disease yielded the following results: pp67 assay positive, 9 of 13 specimens; PCR positive, 13 of 13 specimens; and culture positive, 2 of 13 specimens. After resolution of the discordant results, the following positive and negative predictive values (PPV and NPV, respectively) for the diagnosis of HCMV CNS disease were determined. The PPV for PCR, pp67 assay, and culture were 68.4, 100, and 100%, respectively, and the NPV for PCR, pp67 assay, and culture were 100, 97.0, and 82. 7%, respectively. The sensitivities for DNA PCR, pp67 assay, and culture for the detection of HCMV were 100, 84.6, and 18%, respectively, and the clinical specificities were 90.5, 100, and 100%, respectively. This study indicates that the detection of HCMV pp67 mRNA in CSF has good correlation with active HCMV CNS disease, whereas CSF culture is insensitive and qualitative DNA PCR may detect latent nonreplicating virus in CSF from patients without HCMV CNS disease.

  4. 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

  5. [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.

  6. Monocytes harboring cytomegalovirus: interactions with endothelial cells, smooth muscle cells, and oxidized low-density lipoprotein. Possible mechanisms for activating virus delivered by monocytes to sites of vascular injury.

    Science.gov (United States)

    Guetta, E; Guetta, V; Shibutani, T; Epstein, S E

    1997-07-01

    Cytomegalovirus (CMV) infection and its periodic reactivation from latency may contribute to atherogenesis and restenosis. It is unknown how CMV is delivered to the vessel wall and is reactivated. We examined the following hypothesis: CMV, present in monocytes recruited to sites of vascular injury, is activated by endothelial cell (EC) or smooth muscle cell (SMC) contact and by oxidized low-density lipoproteins (oxLDLs). The CMV major immediate-early promoter (MIEP) controls immediate-early (IE) gene expression, and thereby viral replication. To determine whether elements of the vessel wall can activate CMV present in monocytes, we transiently transfected the promonocytic cell line HL-60 with a chloramphenicol acetyltransferase reporter gene construct driven by MIEP. MIEP activity increased 1.7 +/- 0.5-fold (P = .02) when the transfected HL-60 cells were cocultured with ECs, 4.5 +/- 1.5-fold when cocultured with SMCs (P = .03), and 2.0 +/- 0.5-fold (P = .01) when exposed to oxLDL. The combination of oxLDL and EC coculture increased MIEP activity over 7-fold. We also found that freshly isolated human monocytes, infected with endothelium-passaged CMV, were capable of transmitting infectious virus to cocultured ECs or SMCs. CMV-related progression of atherosclerosis or restenosis may, at least in part, involve monocyte delivery of the virus to the site of vascular injury, where the vascular milieu, ie, contact with ECs, SMCs, and oxLDL, can contribute to viral reactivation and/or replication by enhancing CMV IE gene expression. The virus may then infect neighboring ECs or SMCs, initiating a cascade of events predisposing to the development of atherogenesis-related processes.

  7. 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...

  8. [Follow-up serological study of herpes simplex and cytomegalovirus in Cuban patients infected with human immunodeficiency virus (HIV)].

    Science.gov (United States)

    Resik, S; Santana, E; Rivero, J; Pérez, A B; Kourí, V; Larralde, O

    1997-01-01

    The evolution serological response against the herpes simplex virus and citomegalovirus in HIV infected patients grouped into different stages of the disease was studied. Fluctuations in the TPG of antibodies were observed in these values in a cyclical way through time. There was a greater significant difference among the TPG of antibodies against HSV in the group of asymptomatic patients compared with AIDS patients and with those who died. There is a marked decrease in the TPG of antibodies against HSV and CMV approximately one year before the death of patients.

  9. 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.

  10. 小肠移植术后巨细胞病毒感染二例的治疗体会%Cytomegalovirus infection after small bowel transplantation

    Institute of Scientific and Technical Information of China (English)

    李元新; 李宁; 李幼生; 倪小冬; 吴波; 王剑; 李民; 黎介寿

    2011-01-01

    目的 总结小肠移植术后巨细胞病毒(CMV)感染的治疗经验.方法 1994年至2009年间完成15例小肠移植,分为3个阶段:1994-1995年为第1阶段(3例),2003-2006年为第2阶段(7例),2007年以后为第3阶段(5例).第1阶段术后未进行CMV感染的预防;第2阶段通过肠镜、病理检查和血清学检查(CMV IgM、CMV pp65和CMV DNA)进行CMV感染的诊断,术后静脉注射更昔洛韦2~3周,口服阿昔洛韦3个月以预防CMV感染;第3阶段在第2阶段的基础上,应用实时定量PCR技术检测CMV DNA,并制定计划性监测方案,术后静脉注射更昔洛韦2~3周,口服更昔洛韦3个月预防CMV感染,采用CMV感染的抢先治疗方案.结果 15例患者中有2例(13.3 %)术后发生CMV感染.其中第2阶段1例术后45 d发生移植肠CMV肠炎,术后64 d并发CMV肺炎,应用更昔洛韦和胸腺肽,并停用他克莫司,最终转为重度排斥反应后死亡;第3阶段1例术后第3个月发生CMV感染,经CMV抢先治疗后治愈.结论 小肠移植术后应进行CMV的预防性治疗,严密监测CMV血清学指标,适时进行抢先治疗.对于CMV侵袭性疾病在进行有效治疗的同时应注意排斥反应的发生.%Objective Cytomegalovirus (CMV) has remained the most significant pathogen that threatens the outcome of small bowel transplantation (SBTx). This paper To outline preliminary experience of prophylaxis and treatment of cytomegalovirus (CMV) in 15 cases subject to small bowel transplantation (SBTx) and also review current progress of diagnosis and treatment of CMV.Methods Fifteen cases of SBTx were divided into 3 eras: era Ⅰ (1994-1995)-3 SBTx treated with cyclosporine-based immunosuppression; era Ⅱ (2003-2006)-7 SBTx treated with tacrolimus-based immunosuppression; and era Ⅲ (2007-present)-5 SBTx treated with Alemtuzumab induction therapy and maintenance tacrolimus monotherapy. No antiviral prophylaxis after SBTx was applied during era Ⅰ; in era Ⅱ, ileoscopic and pathological

  11. Retrospective analysis of cytomegalovirus infection in children of Wuhu City%芜湖市患儿巨细胞病毒感染回顾性分析

    Institute of Scientific and Technical Information of China (English)

    苏贵灵; 李光友; 王佐; 潘嘉严

    2014-01-01

    目的:了解芜湖市患儿巨细胞病毒感染状况。方法应用酶联免疫吸附试验对874例可疑巨细胞病毒感染患儿血清CMV-IgM抗体进行检测。结果874例患儿CMV-IgM检出率为4.46%。其中男童阳性26例(26/531),阳性率4.89%;女童阳性13例(13/343),阳性率3.79%;男童与女童CMV-IgM阳性率之间差异无统计学意义(χ2=0.37,P>0.05)。在不同年龄组中,以>6个月~1岁组阳性率最高,达10.19%。其中主要表现依次为肝功能异常、神经系统疾病、黄疸、肺炎。结论芜湖市患儿CMV感染率较高,应引起儿科医生的重视。%Objective To investigate the cytomegalovirus( CMV) infection in children of Wuhu City. Methods Serum samples from children n=874 were tested for CMV-IgM using commercial ELISA kits. Re-sults The CMV-IgM detective rate of serum samples from 874 children was 4. 46%. The positive rate of CMV-IgM was 4. 89%(26/531cases)and 3. 79%(13/343 cases)in boys and girls,respectively. There was no signifi-cant difference in the positive rate of CMV-IgM between boys and girls(χ2 =0. 37,P>0. 05). The positive rate peaked in children at age of >6 months~1 year(10. 19%). Clinical manifestations included liver dysfunction, neurological diseases,jaundice and pneumonia. Conclusion The positive rate of CMV-IgM in children in local district of Wuhu city is high,which should be given due attention.

  12. 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.

  13. Cytomegalovirus immune evasion of myeloid lineage cells.

    Science.gov (United States)

    Brinkmann, Melanie M; Dağ, Franziska; Hengel, Hartmut; Messerle, Martin; Kalinke, Ulrich; Čičin-Šain, Luka

    2015-06-01

    Cytomegalovirus (CMV) evades the immune system in many different ways, allowing the virus to grow and its progeny to spread in the face of an adverse environment. Mounting evidence about the antiviral role of myeloid immune cells has prompted the research of CMV immune evasion mechanisms targeting these cells. Several cells of the myeloid lineage, such as monocytes, dendritic cells and macrophages, play a role in viral control, but are also permissive for CMV and are naturally infected by it. Therefore, CMV evasion of myeloid cells involves mechanisms that qualitatively differ from the evasion of non-CMV-permissive immune cells of the lymphoid lineage. The evasion of myeloid cells includes effects in cis, where the virus modulates the immune signaling pathways within the infected myeloid cell, and those in trans, where the virus affects somatic cells targeted by cytokines released from myeloid cells. This review presents an overview of CMV strategies to modulate and evade the antiviral activity of myeloid cells in cis and in trans.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 婴幼儿人巨细胞病毒感染的临床表现和糖蛋白B基因分型%Clinical manifestations of human cytomegalovirus infection of infants and genotype of glycoprotein B

    Institute of Scientific and Technical Information of China (English)

    陆晓东; 单小云; 袁青; 朱以军; 郑雅萍; 徐瑞龙

    2011-01-01

    Objective: To understand the clinical manifestations of human cytomegalovirus (HCMV) activate infection of infants and its relationship with genotype of glycoprotein B. Methods: ELISA method was used to detect 51 infants with positive HCMV diagnosed by HCMV - IgM, and the different clinical symptoms were analyzed. Genotyping of HCMV glycoprotein B was performed among 43 infants by nested PCR and restriction fragment length polymorphism (RFLP) . Results: Among 51 infants with HCMV infection, 25. 49% of them were systemic infection and 74. 51% of them were single organ infection, the proportions of HCMV inclusion disease and hepatitis were 25.49% and 21.57%, respectively. The results of genotyping of HCMV glycoprotein B among 43 infants: 20 infants with glycoprotein B Ⅰ genotype, 7 infants with glycoprotein B Ⅱ genotype, 9 infants with glycoprotein B Ⅲ genotype, 4 infants with glycoprotein B Ⅰ genotype and glycoprotein B Ⅱ genotype, 2 infants with glycoprotein B Ⅰ genotype and glycoprotein B Ⅲ genotype, one infant with glycoprotein B Ⅱ genotype and glycoprotein B Ⅲ genotype, no infant was found with glycoprotein B Ⅳ genotype; glycoprotein B Ⅰ genotype accounted for 46. 51%.Conclusion: The clinical manifestations of infantile HCMV infection are various; glycoprotein B Ⅰ genotype is in the majority among HCMV infected infants.%目的:了解婴幼儿人巨细胞病毒(HCMV)活动性感染的临床表现,以及与糖蛋白B(gB)基因型的关系.方法:ELISA法检测HCMV-lgM确定的HCMV阳性的婴幼儿51例,对其不同临床症状进行分析.对其中43例患儿使用套式PCR(nPCR)法加限制性长度多态性分析(RFLP)进行HCMV gB基因分型.结果:在51例HCMV感染患儿中全身性感染和单脏器感染分别占25.49%和74.51%,HCMV包涵体病和肝炎分别占25.49%和21.57%.43例患儿HCMV gB的基因分型结果为,gBI型20例,gBⅡ型7例,gBⅢ型9例,gB Ⅰ、Ⅱ混合型4例,gBⅠ、Ⅲ混合型2

  19. 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....

  20. 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.

  1. 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.

  2. Neurological Consequences of Cytomegalovirus Infection

    Science.gov (United States)

    ... handling body fluids or contaminated materials (such as diapers or tissues), avoiding shared dishes, utensils, and other ... handling body fluids or contaminated materials (such as diapers or tissues), avoiding shared dishes, utensils, and other ...

  3. 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

  4. 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.

  5. 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.......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...

  6. Cytomegalovirus retinitis after initiation of antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Zahra Ahmadinejad

    2013-10-01

    Full Text Available Patients with human immunodeficiency virus (HIV infection receiving antiretroviral therapy (ART, despite a reduced viral load and improved immune responses, may experience clinical deterioration. This so called "immune reconstitution inflammatory syndrome (IRIS" is caused by inflammatory response to both intact subclinical pathogens and residual antigens. Cytomegalovirus retinitis is common in HIV-infected patients on ART with a cluster differentiation 4 (CD4+ counts less than 50 cells/mm3. We reported a patient with blurred vision while receiving ART. She had an unmasking classic CMV retinitis after ART.

  7. 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.

  8. Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo

    DEFF Research Database (Denmark)

    Spiess, Katja; Jeppesen, Mads G.; Malmgaard-Clausen, Mikkel

    2015-01-01

    to target the human viral pathogen, human cytomegalovirus (HCMV), on the basis of its expression of the 7TM G protein-coupled chemokine receptor US28. The virus origin of US28 provides an exceptional chemokine-binding profile with high selectivity and improved binding for the CX3C chemokine, CX3CL1......The use of receptor-ligand interactions to direct toxins to kill diseased cells selectively has shown considerable promise for treatment of a number of cancers and, more recently, autoimmune disease. Here we move the fusion toxin protein (FTP) technology beyond cancer/autoimmune therapeutics...

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Mirjam Steingruber

    2015-08-01

    Full Text Available 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.

  11. 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

  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. 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.

  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. Cytomegalovirus in pregnancy and the neonate

    Science.gov (United States)

    Emery, Vincent C.; Lazzarotto, Tiziana

    2017-01-01

    Congenital cytomegalovirus (CMV) remains a leading cause of disability in children. Understanding the pathogenesis of infection from the mother via the placenta to the neonate is crucial if we are to produce new interventions and provide supportive mechanisms to improve the outcome of congenitally infected children. In recent years, some major goals have been achieved, including the diagnosis of primary maternal CMV infection in pregnant women by using the anti-CMV IgG avidity test and the diagnosis and prognosis of foetal CMV infection by using polymerase chain reaction real-time tests to detect and quantify the virus in amniotic fluid. This review summarises recent advances in our understanding and highlights where challenges remain, especially in vaccine development and anti-viral therapy of the pregnant woman and the neonate. Currently, no therapeutic options during pregnancy are available except those undergoing clinical trials, whereas valganciclovir treatment is recommended for congenitally infected neonates with moderately to severely symptomatic disease. PMID:28299191

  16. 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.

  17. Seropositivity of cytomegalovirus in patients with recurrent pregnancy loss

    OpenAIRE

    Roya Sherkat; Mohsen Meidani; Hossein Zarabian; Abbas Rezaei; Ali Gholamrezaei

    2014-01-01

    Background: Some evidence has shown a relationship between human cytomegalovirus (CMV) infection and pregnancy loss. However, whether recurrent or latent CMV infection or altered immune response to CMV is related to recurrent pregnancy loss (RPL) is unclear. We evaluated CMV infection and avidity of antibodies to CMV in women with RPL. Materials and Methods: This case-control study was conducted on 43 women with RPL referred to a clinical immunology out-patient clinic in Isfahan (Iran), and 4...

  18. Human cytomegalovirus-encoded UL33 and UL78 heteromerize with host CCR5 and CXCR4 impairing their HIV coreceptor activity.

    Science.gov (United States)

    Tadagaki, Kenjiro; Tudor, Daniela; Gbahou, Florence; Tschische, Pia; Waldhoer, Maria; Bomsel, Morgane; Jockers, Ralf; Kamal, Maud

    2012-05-24

    Human cytomegalovirus (HCMV) encodes four 7-transmembrane-spanning (7TM) proteins, US28, US27, UL33, and UL78, which present important sequence homology with human chemokine receptors. Whereas US28 binds a large range of chemokines and disturbs host cell signaling at different levels, the others are orphans with largely unknown functions. Assembly of 2 different 7TM proteins into hetero-oligomeric complexes may profoundly change their respective functional properties. We show that HCMV-encoded UL33 and UL78 form heteromers with CCR5 and CXCR4 chemokine receptors in transfected human embryonic kidney 293T cells and monocytic THP-1 cells. Expression of UL33 and UL78 had pleiotropic, predominantly negative, effects on CCR5 and CXCR4 cell surface expression, ligand-induced internalization, signal transduction, and migration without modifying the chemokine binding properties of CCR5 and CXCR4. Importantly, the coreceptor activity of CCR5 and CXCR4 for HIV was largely impaired in the presence of UL33 and UL78 without affecting expression of the primary HIV entry receptor CD4 and its interaction with CCR5 and CXCR4. Collectively, we identified the first molecular function for the HCMV-encoded orphan UL33 and UL78 7TM proteins, namely the regulation of cellular chemokine receptors through receptor heteromerization.

  19. Interferon-alpha subtype 11 activates NK cells and enables control of retroviral infection.

    Directory of Open Access Journals (Sweden)

    Kathrin Gibbert

    Full Text Available The innate immune response mediated by cells such as natural killer (NK cells is critical for the rapid containment of virus replication and spread during acute infection. Here, we show that subtype 11 of the type I interferon (IFN family greatly potentiates the antiviral activity of NK cells during retroviral infection. Treatment of mice with IFN-α11 during Friend retrovirus infection (FV significantly reduced viral loads and resulted in long-term protection from virus-induced leukemia. The effect of IFN-α11 on NK cells was direct and signaled through the type I IFN receptor. Furthermore, IFN-α11-mediated activation of NK cells enabled cytolytic killing of FV-infected target cells via the exocytosis pathway. Depletion and adoptive transfer experiments illustrated that NK cells played a major role in successful IFN-α11 therapy. Additional experiments with Mouse Cytomegalovirus infections demonstrated that the therapeutic effect of IFN-α11 is not restricted to retroviruses. The type I IFN subtypes 2 and 5, which bind the same receptor as IFN-α11, did not elicit similar antiviral effects. These results demonstrate a unique and subtype-specific activation of NK cells by IFN-α11.

  20. Childhood environments and cytomegalovirus serostatus and reactivation in adults

    NARCIS (Netherlands)

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

    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. 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.

  2. Case of cytomegalovirus-associated direct anti-globulin test-negative autoimmune hemolytic anemia.

    Science.gov (United States)

    Kaneko, Saeko; Sato, Masanori; Sasaki, Goro; Eguchi, Hiroyuki; Oishi, Tsutomu; Kamesaki, Toyomi; Kawaguchi, Hiroyuki

    2013-12-01

    A 1-year-old boy developed autoimmune hemolytic anemia after a negative direct anti-globulin test. The concentration of erythrocyte membrane-associated immunoglobulin G, determined using an immunoradiometric assay, correlated with disease activity. He was positive for cytomegalovirus (CMV) both serologically and by quantitative real-time polymerase chain reaction, indicating that his autoimmune hemolytic anemia was directly caused by CMV infection. Since anti-CMV immunoglobulin G was not absorbed by the patient's erythrocytes, cross-reaction between erythrocyte antigens and CMV was not likely a causative factor for hemolysis.

  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. Preconceptual administration of an alphavirus replicon UL83 (pp65 homolog) vaccine induces humoral and cellular immunity and improves pregnancy outcome in the guinea pig model of congenital cytomegalovirus infection.

    Science.gov (United States)

    Schleiss, Mark R; Lacayo, Juan C; Belkaid, Yasmine; McGregor, Alistair; Stroup, Greg; Rayner, Jon; Alterson, Kimberly; Chulay, Jeffrey D; Smith, Jonathan F

    2007-03-15

    Development of a vaccine against congenital cytomegalovirus (CMV) infection is a major public health priority. We report the use of a propagation-defective, single-cycle, RNA replicon vector system, derived from an attenuated strain of the alphavirus Venezuelan equine encephalitis virus, to produce virus-like replicon particles (VRPs) expressing GP83, the guinea pig CMV (GPCMV) homolog of the human CMV pp65 phosphoprotein. Vaccination with VRP-GP83 induced antibodies and CD4(+) and CD8(+) T cell responses in GPCMV-seronegative female guinea pigs. Guinea pigs immunized with VRP-GP83 vaccine or with a VRP vaccine expressing influenza hemagglutinin (VRP-HA) were bred for pregnancy and subsequent GPCMV challenge during the early third trimester. Dams vaccinated with VRP-GP83 had improved pregnancy outcomes, compared with dams vaccinated with the VRP-HA control. For VRP-GP83-vaccinated dams, there were 28 live pups and 4 dead pups (13% mortality) among 10 evaluable litters, compared with 9 live pups and 12 dead pups (57% mortality) among 8 evaluable litters in the VRP-HA-vaccinated group (P<.001, Fisher's exact test). Improved pregnancy outcome was accompanied by reductions in maternal blood viral load, measured by real-time polymerase chain reaction. These results indicate that cell-mediated immune responses directed against a CMV matrix protein can protect against congenital CMV infection and disease.

  5. PKR-like endoplasmic reticulum kinase is necessary for lipogenic activation during HCMV infection.

    Directory of Open Access Journals (Sweden)

    Yongjun Yu

    Full Text Available PKR-like endoplasmic reticulum (ER kinase (PERK is an ER-associated stress sensor protein which phosphorylates eukaryotic initiation factor 2α (eIF2α to induce translation attenuation in response to ER stress. PERK is also a regulator of lipogenesis during adipocyte differentiation through activation of the cleavage of sterol regulatory element binding protein 1 (SREBP1, resulting in the upregulation of lipogenic enzymes. Our recent studies have shown that human cytomegalovirus (HCMV infection in human fibroblasts (HF induces adipocyte-like lipogenesis through the activation of SREBP1. Here, we report that PERK expression is highly increased in HCMV-infected cells and is necessary for HCMV growth. Depletion of PERK, using short hairpin RNA (shRNA, resulted in attenuation of HCMV growth, inhibition of lipid synthesis and reduction of lipogenic gene expression. Examination of the cleavage of SREBP proteins showed PERK depletion inhibited the cleavage of SREBP1, but not SREBP2, in HCMV-infected cells, suggesting different cleavage regulatory mechanisms for SREBP1 and 2. Further studies showed that the depletion of SREBP1, but not SREBP2, reduced lipid synthesis in HCMV infection, suggesting that activation of SREBP1 is sufficient to induce lipogenesis in HCMV infection. The reduction of lipid synthesis by PERK depletion can be partially restored by expressing a Flag-tagged nuclear form of SREBP1a. Our studies also suggest that the induction of PERK in HCMV-infected cells stimulates SREBP1 cleavage by reducing levels of Insig1 (Insulin inducible gene 1 protein; this occurs independent of the phosphorylation of eIF2α. Introduction of an exogenous Insig1-Myc into HCMV infected cells significantly reduced HCMV growth and lipid synthesis. Our data demonstrate that the induction of PERK during HCMV infection is necessary for full activation of lipogenesis; this effect appears to be mediated by limiting the levels of Insig1 thus freeing SREBP1-SCAP

  6. PKR-like endoplasmic reticulum kinase is necessary for lipogenic activation during HCMV infection.

    Science.gov (United States)

    Yu, Yongjun; Pierciey, Francis J; Maguire, Tobi G; Alwine, James C

    2013-01-01

    PKR-like endoplasmic reticulum (ER) kinase (PERK) is an ER-associated stress sensor protein which phosphorylates eukaryotic initiation factor 2α (eIF2α) to induce translation attenuation in response to ER stress. PERK is also a regulator of lipogenesis during adipocyte differentiation through activation of the cleavage of sterol regulatory element binding protein 1 (SREBP1), resulting in the upregulation of lipogenic enzymes. Our recent studies have shown that human cytomegalovirus (HCMV) infection in human fibroblasts (HF) induces adipocyte-like lipogenesis through the activation of SREBP1. Here, we report that PERK expression is highly increased in HCMV-infected cells and is necessary for HCMV growth. Depletion of PERK, using short hairpin RNA (shRNA), resulted in attenuation of HCMV growth, inhibition of lipid synthesis and reduction of lipogenic gene expression. Examination of the cleavage of SREBP proteins showed PERK depletion inhibited the cleavage of SREBP1, but not SREBP2, in HCMV-infected cells, suggesting different cleavage regulatory mechanisms for SREBP1 and 2. Further studies showed that the depletion of SREBP1, but not SREBP2, reduced lipid synthesis in HCMV infection, suggesting that activation of SREBP1 is sufficient to induce lipogenesis in HCMV infection. The reduction of lipid synthesis by PERK depletion can be partially restored by expressing a Flag-tagged nuclear form of SREBP1a. Our studies also suggest that the induction of PERK in HCMV-infected cells stimulates SREBP1 cleavage by reducing levels of Insig1 (Insulin inducible gene 1) protein; this occurs independent of the phosphorylation of eIF2α. Introduction of an exogenous Insig1-Myc into HCMV infected cells significantly reduced HCMV growth and lipid synthesis. Our data demonstrate that the induction of PERK during HCMV infection is necessary for full activation of lipogenesis; this effect appears to be mediated by limiting the levels of Insig1 thus freeing SREBP1-SCAP complexes for

  7. 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

  8. Cytomegalovirus pp65 limits dissemination but is dispensable for persistence

    OpenAIRE

    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

    2014-01-01

    The most abundantly produced virion protein in human cytomegalovirus (HCMV) is the immunodominant phosphoprotein 65 (pp65), which is frequently included in CMV vaccines. Although it is nonessential for in vitro CMV growth, pp65 displays immunomodulatory functions that support a potential role in primary and/or persistent infection. To determine the contribution of pp65 to CMV infection and immunity, we generated a rhesus CMV lacking both pp65 orthologs (RhCMVΔpp65ab). While ...

  9. Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

    Science.gov (United States)

    Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

    2016-12-01

    We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients.

  10. 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.

  11. Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Albrecht, T.; Cohrs, R.

    2009-01-01

    The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering

  12. The Human Cytomegalovirus MHC Class I Homolog UL18 Inhibits LIR-1+ but Activates LIR-1− NK Cells1

    OpenAIRE

    Prod’Homme, Virginie; Griffin, Cora; Rebecca J. Aicheler; Wang, Eddie C.Y.; McSharry, Brian P.; Rickards, Carole R.; Stanton, Richard J; Borysiewicz, Leszek K.; López-Botet, Miguel; Wilkinson, Gavin W. G.; Tomasec, Peter

    2007-01-01

    The inhibitory leukocyte Ig-like receptor 1 (LIR-1, also known as ILT2, CD85j, or LILRB1) was identified by its high affinity for the human CMV (HCMV) MHC class I homolog gpUL18. The role of this LIR-1-gpUL18 interaction in modulating NK recognition during HCMV infection has previously not been clearly defined. In this study, LIR-1+ NKL cell-mediated cytotoxicity was shown to be inhibited by transduction of targets with a replication-deficient adenovirus vector encoding UL18 (RAd-UL18). Fibro...

  13. 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.

  14. 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...

  15. 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

  16. 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

  17. Epstein-Barr and cytomegalovirus DNA salivary shedding correlate with long-term plasma HIV RNA detection in HIV-infected men who have sex with men.

    Science.gov (United States)

    Scaggiante, Renzo; Andreis, Samantha; Basso, Monica; Franchin, Elisa; Franzetti, Marzia; Del Vecchio, Claudia; Torti, Carlo; Mengoli, Carlo; Cruciani, Mario; Sarmati, Loredana; Palù, Giorgio; Parisi, Saverio Giuseppe

    2016-07-01

    The aim of the study was to evaluate cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA salivary shedding in HIV-positive men who have sex with men (MSM) and to determine whether viro-immunological parameters and long-term (24 months) plasma HIV RNA (pHIV) detection may predict herpesviruses replication. A total of 193 HIV-positive MSM were consecutively recruited (mean CD4+ cell count 607 cells/mm(3) and mean nadir value 333 cells/mm(3) ); pHIV was analyzed for 24 months prior to saliva sampling: patients were categorized as successfully suppressed (SS) and not suppressed (NS). The EBV viral load was categorized as high viral load (HVL), intermediate (IVL), or low (LVL), CMV DNA as positive or negative. NS patients experienced both herpesviruses detectability more frequently respect to SS patients (P = 0.034); conversely, no salivary shedding was more frequent in SS patients (P = 0.014). HVL EBV was more frequent in NS patients than in SS subjects (P = 0.038 for isolated EBV detection and P = 0.001 when CMV shedding was associated). NS subjects with HVL EBV had a median pHIV of 43,820 copies/ml, significantly higher respect to IVL and LVL patients (P = 0.027 and P = 0.0005, respectively). CMV shedding was mostly associated to EBV shedding. NS patients showed a significantly higher frequency of saliva HVL EBV detection compared to SS patients; moreover, NS patients with HVL EBV had a higher pHIV respect to those with IVL and LVL shedding. Our results suggest that a successful pHIV suppression could reduce the burden of salivary EBV replication and likely the risk of herpesviruses-related cancers.

  18. Amebic and cytomegalovirus colitis mimic ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Meng-Tzu Weng

    2016-06-01

    Full Text Available Here we present a 50-year-old man who suffered from progressively bloody diarrhea for 2 months. A colonoscopy revealed pancolonic mucosal inflammation, ulceration, and spontaneous bleeding. Ulcerative colitis was initially diagnosed and sulfasalazine was prescribed. Hypoalbuminemia and renal function deterioration developed 1 year later. Steroids were prescribed for suspected nephrotic syndrome. His bloody diarrhea and abdominal symptoms worsened after steroid use. Progressive sepsis and acute renal function deterioration also developed. Positive human immunodeficiency virus (HIV antibody was found during routine hemodialysis screening. An episode of colon perforation occurred and surgery was performed. The resected colon showed amoeba, cytomegalovirus, and fungal infection. The patient died of sepsis. In this report, we discuss how to diagnose ulcerative colitis. It is important to exclude infection before using an immunosuppressive agent.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Clinical relevance between human cytomegalovirus infection and colorectal cancer%人巨细胞病毒感染与大肠癌临床相关性

    Institute of Scientific and Technical Information of China (English)

    叶梦思; 何云; 杨守醒; 林豪; 薛战雄; 蔡振寨

    2016-01-01

    目的:探讨大肠癌患者人巨细胞病毒(human cytomegalovirus,HCMV)感染情况及其临床相关性.方法:采用化学发光(CLIA)法对大肠癌组∽=60)、大肠息肉组0=60)及健康对照组∞=60)的外周血清进行HCMV免疫球蛋白G(immunoglobulin G,lgG)、IgM抗体检测;巢式PCR技术结合原位杂交方法检测32例大肠癌组织及癌旁正常肠黏膜组织中HCMV-UL 138基因表达;用Fisher确切概率法比较两组间阳性率,均数比较采用t检验或单因素方差分析.P<0.05为差异有统计学意义.结果:大肠癌组、大肠息肉组、健康对照组血清HCMV-IgG阳性率为分别为95.0%(57/60)、98.3%(59/60)、96.7%(58/60);血清HCMV-IgM阳性率分别为5.0%(3/60)、1.7%(1/60)、1.7%(1/60),3组血清HCMV-IgG、IgM差异无统计学意义(P>0.05).32例大肠癌组织巢式PCR检测HCMV-UL138阳性率为65.6%(19/32),相应癌旁正常肠黏膜组织中为12.5%(4/32),原位杂交法检测癌组织HCMV-UL138阳性率为62.5%(20/32),癌旁正常肠黏膜组织中为9.4%(3/32),大肠癌组织HCMV阳性检出率较癌旁正常组织显著升高(P<0.01).未发现HCMV感染与大肠癌患者的年龄、性别、肿块位置、肿块大小、组织病理分化类型、转移及Dukes分期有显著性关联.结论:大肠癌组织中存在HCMV感染,且HCMV相较于癌旁正常组织更倾向感染癌灶,提示HCMV感染可能参与大肠癌的发生发展过程.

  4. Neonatal gastrointestinal involvement and congenital cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alessandro Porta

    2016-11-01

    Full Text Available Cytomegalovirus (CMV is the most common cause of congenital viral infection, affecting 0.2 to 2.3% of all live births in developed countries. Very low birth weight and extremely low birth weight newborns are at higher risk of symptomatic CMV infection, most commonly secondary and acquired through breast milk. Gastrointestinal involvement is rare in acquired CMV infections, but it could be an important manifestation of postnatal infection in preterm infants admitted to neonatal intensive care units. Early onset of CMV gastrointestinal signs/symptoms is very rare. In a review of the literature it is described in 5 newborns in the first 24 hours of life, and 6 considering the onset in the first week of life. This review describes also a case report of congenital CMV in an immunocompetent newborn with onset of gastrointestinal signs immediately after birth: a possible association between viral infection and enteric manifestations was considered in the differential diagnosis. A review of the literature of the different case reports found has done, with description and comparison of the different patients and clinical presentations.

  5. HCMV感染影响HUVEC中ADAMTS13表达水平的研究%Study on the effect of human cytomegalovirus infection on the ADAMTS13 expression level of human umbilical vein endothelial cells

    Institute of Scientific and Technical Information of China (English)

    何文竹; 尹宗智; 魏兆莲; 李韵

    2015-01-01

    目的:探讨人巨细胞病毒( HCMV)感染对人脐静脉内皮细胞( HUVEC)中ADAMTS13表达水平的影响. 方法:通过培养原代HUVEC,建立HCMV感染HUVEC细胞模型. Western blot法检测 HUVEC 细胞中 ADAMTS13 蛋白表达水平的情况. 结果:100 PFU或更高毒力的 HCMV 可感染 HUVEC 细胞,导致明显的细胞病变:病毒感染后24h,细胞部分开始出现变圆,细胞内颗粒增多;48h后,部分细胞开始出现细胞膜破裂、细胞坏死;随着病毒感染时间的延长,细胞坏死比例逐渐增加. 原代培养的HUVEC细胞裂解液及细胞上清中均有大量的ADAMTS13表达;与未感染HCMV细胞比较,感染HCMV 48h后,HUVEC细胞裂解液及细胞上清中的ADAMTS13蛋白表达水平均显著下降,差异具有显著性( P<0 . 05 ). 结论:HCMV可感染HUVEC并通过抑制细胞中ADAMTS13的表达促进血栓形成.%Objective:To explore the human cytomegalovirus ( HCMV ) infection on ADAMTS13 expression level of human umbilical vein endothelial cells ( HUVEC ) . Methods:By cultivating the original generation of HUVEC,the HCMV infection HUVEC cell model was established . Western blot was used to detect the ADAMTS13 protein expression level of HUVEC cells. Results:100 PFU or higher toxicity of HCMV infected HUVEC cells,lead to obvious cell lesions:24h after virus infection,membrane of part cells turned round and the intracellular par-ticles increased. After 48h infection,some cells began to membrane of rupture,and cellular nei-roses appeared. With the extension of the time of infection,cell death ratio increased gradually. Primary cultured HUVEC cell lysates and cell supernatants showed high expression of AD-AMTS13. Compared with uninfected cells,48h after HCMV infection,ADAMTS13 protein levels of HUVEC cell lysates and cell supernatants significantly decreased ( P<0 . 05 ) . Conclusion:HCMV can infect HUVEC and may promote the formation of thrombosis by inhibiting the ex-pression of ADAMTS13 in cells.

  6. Bacterial Muramyl Dipeptide (MDP) Restricts Human Cytomegalovirus Replication via an IFN-β-Dependent Pathway.

    Science.gov (United States)

    Kapoor, Arun; Fan, Yi-Hsin; Arav-Boger, Ravit

    2016-02-02

    We recently reported that induction of NOD2 by human Cytomegalovirus (HCMV) resulted in virus inhibition and upregulation of antiviral and inflammatory cytokines. Here we investigated the effects of muramyl dipeptide (MDP), a bacterial cell wall component that activates NOD2, on HCMV replication and antiviral responses. HCMV infection of human foreskin fibroblasts induced NOD2, the downstream receptor-interacting serine/threonine-protein kinase 2 (RIPK2), resulting in phosphorylation of TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3). MDP treatment following infection at low multiplicity (MOI = 0.1 PFU/cell) inhibited HCMV in a dose-dependent manner and further induced phosphorylation of TBK1, IRF3 and expression of IFN-β. None of these effects of MDP were observed following infection at multiplicity of 1. In infected NOD2 knocked-down cells MDP did not induce IFN-β, irrespective of MOI. Treatment with MDP before infection also inhibited HCMV, an effect augmented with treatment duration. Treatment with an IFN-β receptor blocking antibody or knockdown of IFN-β significantly attenuated the inhibitory effect of MDP on HCMV. MDP treatment before or after infection with herpesvirus 1 did not inhibit its replication. Summarized, NOD2 activation exerts anti-HCMV activities predominantly via IFN-β. Since MDP is a bacterial cell wall component, ongoing microbial exposure may influence HCMV replication.

  7. 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.

  8. Effect of combination antiretroviral therapy on cytomegalovirus retinitis

    Directory of Open Access Journals (Sweden)

    Banker Alay

    2002-01-01

    Full Text Available Purpose: To study the various changes in the course of cytomegalovirus (CMV retinitis following combination antiretroviral treatment. Methods: Combination antiretroviral treatment was given to 12 patients with active CMV retinitis following which all anti-CMV medications were discontinued once the CD4 cell counts were> 100/mm3 for 3 months. Results: The median CD4 cell count increased from 36.5/mm3 (range, 3-74/mm3 at baseline to 175.5/mm3 (range, 97-410/mm3 at 3 months. No patient had reactivation of CMV retinitis or developed extraocular CMV infection during median follow-up of 16.7 months. In one patient with peripheral active CMV retinitis, the retinitis resolved completely and remained so throughout the follow-up period without specific anti-CMV treatment. Five (41.7% patients had immune recovery vitritis. Conclusion: Patients receiving combination antiretroviral treatment following treatment for CMV retinitis have better control of CMV retinitis but immune recovery vitritis is a common sequelae. Reactivation of CMV retinitis is common in patients who discontinue combination antiretroviral treatment

  9. 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

  10. 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

  11. Prevalência de infecção congênita por citomegalovírus em recém-nascidos de uma unidade de tratamento intensivo de um hospital público The prevalence of congenital cytomegalovirus infection in newborn infants at an intensive care unit in a public hospital

    Directory of Open Access Journals (Sweden)

    Clarissa Schreiner Miura

    2006-02-01

    Full Text Available OBJETIVO: Determinar a prevalência da infecção congênita por citomegalovírus em recém-nascidos internados na unidade de terapia intensiva neonatal de um hospital público de Porto Alegre. METODOS: Estudo transversal, incluindo 261 recém-nascidos que nasceram em um hospital público da cidade de Porto Alegre no ano de 2003 e foram internados na unidade de terapia intensiva neonatal. Foi coletada amostra de urina nos primeiros 7 dias de vida e realizado o teste de reação em cadeia da polimerase para a pesquisa do DNA do citomegalovírus. RESULTADOS: A prevalência de infecção congênita por citomegalovírus na população estudada foi de 0,8% (IC 95%: 0,097-2,86. Devido à baixa prevalência, não foi possível associar fatores de risco. CONCLUSÕES: A prevalência de infecção congênita por citomegalovírus em uma unidade de terapia intensiva neonatal de um hospital público de Porto Alegre não foi considerada elevada, sendo semelhante à prevalência encontrada em outros estudos realizados.OBJECTIVE: To determine the prevalence of congenital cytomegalovirus infection in newborn infants admitted to an intensive care unit in a public hospital in Porto Alegre. METHODS: A cross-sectional study of 261 newborn infants born at a public hospital in the city of Porto Alegre in 2003 and admitted to the intensive care ward. Urine samples were collected within 7 days of birth and a polymerase chain reaction-PCR performed to test for cytomegalovirus DNA. RESULTS: The prevalence of congenital cytomegalovirus infection among the study population was 0.8% (95% CI: 0.097%-2.86%. It was not possible to assess risk factors because this prevalence was so low. CONCLUSIONS: The prevalence of congenital cytomegalovirus infection in an intensive care unit at a public hospital in Porto Alegre was not considered elevated and was comparable with prevalence rates found by other studies.

  12. Murine cytomegalovirus protein pM92 is a conserved regulator of viral late gene expression.

    Science.gov (United States)

    Chapa, Travis J; Perng, Yi-Cheih; French, Anthony R; Yu, Dong

    2014-01-01

    In this study, we report that murine cytomegalovirus (MCMV) protein pM92 regulates viral late gene expression during virus infection. Previously, we have shown that MCMV protein pM79 and its human cytomegalovirus (HCMV) homologue pUL79 are required for late viral gene transcription. Identification of additional factors involved is critical to dissecting the mechanism of this regulation. We show here that pM92 accumulated abundantly at late times of infection in a DNA synthesis-dependent manner and localized to nuclear viral replication compartments. To investigate the role of pM92, we constructed a recombinant virus SMin92, in which pM92 expression was disrupted by an insertional/frameshift mutation. During infection, SMin92 accumulated representative viral immediate-early gene products, early gene products, and viral DNA sufficiently but had severe reduction in the accumulation of late gene products and was thus unable to produce infectious progeny. Coimmunoprecipitation and mass spectrometry analysis revealed an interaction between pM92 and pM79, as well as between their HCMV homologues pUL92 and pUL79. Importantly, we showed that the growth defect of pUL92-deficient HCMV could be rescued in trans by pM92. This study indicates that pM92 is an additional viral regulator of late gene expression, that these regulators (represented by pM92 and pM79) may need to complex with each other for their activity, and that pM92 and pUL92 share a conserved function in CMV infection. pM92 represents a potential new target for therapeutic intervention in CMV disease, and a gateway into studying a largely uncharted viral process that is critical to the viral life cycle.

  13. SPONTANEOUS PNEUMOPERICARDIUM RELATED TO ACTIVE CYTOMEGALOVIRAL INFECTION IN A LUNG-TRANSPLANT RECIPIENT

    NARCIS (Netherlands)

    MANNES, GPM; VANDERBIJ, W

    1995-01-01

    Spontaneous pneumopericardium occurred in a patient almost 4 weeks after bilateral lung transplantation for cystic fibrosis. The patient had no specific complaints and was in stable haemodynamic condition. We suggest that this pneumopericardium was related to a concomitant active cytomegalovirus (CM

  14. 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.

  15. 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.

  16. 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

  17. Acute cervicitis and vulvovaginitis may be associated with Cytomegalovirus.

    Science.gov (United States)

    Abou, Magali; Dällenbach, Patrick

    2013-04-19

    Cytomegalovirus (CMV) infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosic syndrome. Its association with acute cervicitis and vulvovaginitis has rarely been reported. A 24-year-old woman presented with pelvic pain, vulvodynia, abnormal vaginal discharge, burning with urination, fatigue, fever, vomiting and diarrhoea. The vulva and cervix were red with vesicular lesions on the cervix. Genital herpes simplex infection (HSV) was suspected and valacyclovir was given orally. However, serial viral cultures performed 7 weeks apart did not isolate HSV as suspected, but CMV was confirmed by immunofluorescence and early antigen research. Blood tests confirmed an acute CMV infection. Typical inclusions were found at histology. Symptoms resolved slowly with persistence of cervical lesions at 7 weeks from diagnosis. The frequency of CMV genital infection is probably underestimated. The infection is not always asymptomatic and might be confused with genital HSV infection. The clinical course is longer.

  18. 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...

  19. Seroprevalence of cytomegalovirus infection among healthy blood donors in Bahia State, Brazil Soroprevalência da infecção por citomegalovírus entre doadores de sangue saudáveis no estado da Bahia, Brasil

    Directory of Open Access Journals (Sweden)

    Sócrates B. Matos

    2010-02-01

    Full Text Available We aimed at analyzing the seroprevalence of cytomegalovirus infection (CMV and to assess particular aspects of the related immunological profile among blood donors in the State of Bahia, Brazil. Immunoassays were performed to detect anti-CMV IgG and IgM antibodies and the anti-CMV IgG avidity was evaluated. The methodology used was Enzyme Linked Immuno Sorbent Assay (ELISA with results being confirmed by chemiluminescence. Reactivity to CMV was compared between genders and age groups. Among the 636 healthy blood donors tested, 428 (67.3% were men and 208 (32.7% were women. The overall seroprevalence of CMV was 87.9%; seroprevalence was statistically higher in women (94.7% than in men (84.6% - pNós objetivamos analisar a soroprevalência para infecção por citomegalovírus (CMV e avaliar aspectos particulares do perfil imunológico relacionado em doadores de sangue no estado da Bahia. Foram realizados imunoensaios de detecção de IgG e IgM anti-CMV, bem como avaliação da avidez dos anticorpos IgG anti-CMV. A metodologia utilizada foi o Teste imunoenzimático ELISA, confirmado por quimioluminescência. A reatividade das amostras para a infecção por CMV foi comparada entre gêneros e grupos etários. Entre os 636 doadores testados, 428 (67,3% eram do sexo masculino e 208 (32,7% do sexo feminino. A soroprevalência geral para CMV observada foi de 87,9%, sendo maior estatisticamente entre as mulheres (94,7% do que entre os homens (84,6% (p<0,05. Nenhuma amostra foi positiva para IgM anti-CMV. Cerca de 4,6% das amostras testadas apresentaram IgG anti-CMV em altos títulos, nestes casos foi realizado o imunoensaio de avidez do IgG anti-CMV que evidenciou: baixa avidez (31%, moderada avidez (21% e alta avidez (48%. A alta soroprevalência encontrada ressalta a importância do uso de estratégias como a leucorredução e a transfusão com hemocomponente CMV-negativo em pacientes com alto risco de desenvolverem infecção severa por CMV. Os altos t

  20. [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).

  1. Vesicular Stomatitis Virus Infection Promotes Immune Evasion by Preventing NKG2D-Ligand Surface Expression

    DEFF Research Database (Denmark)

    Jensen, Helle; Andresen, Lars; Nielsen, Jens

    2011-01-01

    leads to a robust induction of MICA mRNA expression, however the subsequent surface expression is potently hindered. Thus, VSV lines up with human cytomegalovirus (HCMV) and adenovirus, which actively subvert the immune system by negatively affecting NKG2D-ligand surface expression. VSV infection caused...

  2. 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.

  3. 人巨细胞病毒感染与高血压的关系研究%Relationship between human cytomegalovirus infections and high blood pressure

    Institute of Scientific and Technical Information of China (English)

    苏怀勇; 鹿克风; 侯晓阳; 王勇; 李敏

    2015-01-01

    目的:比较高血压患者群体与健康人群的人巨细胞病毒(HCM V )感染率及血浆中和抗体水平,探讨 HC‐M V感染率与高血压的关系,为预防和治疗高血压提供临床依据。方法选取2013年12月-2014年12月在医院接受治疗的60例高血压患者作为观察组,同期选取60名健康体检者作为对照组,比较两组受试者临床资料,数据采用SPSS 19.0软件进行统计分析。结果 HCM V的阳性率观察组为78.33%、对照组28.33%,观察组HCMV UL93DAN、HCMV IgG 及 HCMV IgM 阳性率分别为71.67%、70.00%及41.67%,对照组分别为55.00%、56.67%及3.33%;HCM V特异性中和抗体检测观察组集合滴度为37.55±20.06,对照组集合滴度为59.69±24.32;各项指标结果对照组均优于观察组,其中HCMV、HCMV UL93DNA及HCMV IgG的结果比较,差异有统计学意义(P<0.05)。结论高血压患者 HCMV感染率显著高于健康人群,特异性中和抗体水平降低,说明 HCM V体液免疫状态低下,人巨细胞病毒与高血压显著相关。%OBJECTIVE To compare the HCMV infection rates and plasma neutralizing antibody levels in patients with high blood pressure and healthy people and to discuss the relationship between HCMV infection rate and high blood pressure ,so as to provide clinical basis for the prevention and treatment of high blood pressure .METHODS Totally 60 cases of high blood pressure patients admitted from Dec .2013 to Dec .2014 were chosen as observation group .In the same period ,60 healthy people were chosen as control group .The clinical data of the two groups were compared .All data were statistically analyzed by SPSS 19 .0 .RESULTS The observation group had the HC‐MV positive ratio of 78 .33% ,while the control group got 28 .33% .The positive rates of HCMV UL93DAN , HCMV IgG and HCMV IgM of the observation group were 71 .67% ,70 .00% and 41 .67% respectively ,while 55

  4. 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.

  5. 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…

  6. Clinical observation for cytomegalovirus infection of infant idiopathic thrombocytopenic purpura%婴儿特发性血小板减少性紫癜巨细胞病毒感染临床观察

    Institute of Scientific and Technical Information of China (English)

    王欣; 乔丽津

    2011-01-01

    Objective To investigate the effect of cytomegalovirus (CMV) infection on the patho-genesis of infant idiopathic thrombocytopenic purpura (FTP). Methods IgM/DNA of serum CMV were detected in 178 cases of infants ITP in our hospital from June of 2004 to December of 2009. According to the results of positive or negative, they were divided into observation group and control group. Their ages of onset, course of disease, inducing factors, bleeding degrees, lab examinations and outcome were analyzed retrospectively. Results The median ages of observation group (81 cases) and control group (97 cases) were three months and six months respectively; The prodromal infection rate for both groups were 37% and 42% respectively and there was no statistical difference (P >0. 05). The prodromal infection was mainly upper respiratory tract infection; 72% and 75% patients in two groups had vaccination history and there was no statistical difference ( P > 0.05); The degrees of bleeding in two groups had no statistical difference (P >0.05). The platelet counts of over half patients were less than 10 ×109/L when admitted into hospital. The mean values were 12.28 × 109/L and 11.67 × 109/L respectively and showed no statistical difference ( P > 0.05); The bone marrow smears of two groups appeared normal or increased number of megakaryocyte combined with maturation arrest and thrombocyte dysplasia; 86% (31/36) and 81% (26/32) patients in two groups had abnormal immunoglobulin and there was no statistical difference (P > 0.05). After treatment of prednisone and/or venous gamma globulin, the platelet counts of 75 cases (93% ) and 93 cases (96% ) in two groups turned to normal and there was no statistical difference ( P > 0. 05 ). Conclusions CMV infection is very common in small children and may be one of inducing factors for thrombocytopenic purpura. Clinical manifestation of ITP patients has no significant difference whether they have CMY infection or not. Infant ITP with or without

  7. 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.

  8. 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

  9. 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

  10. BALB/c mice model of cytomegalovirus-induced myocarditis

    Institute of Scientific and Technical Information of China (English)

    Yi Xu; Feng Fang; Zhidan Xiang; Hong zeng; Ge Li

    2005-01-01

    Objective: A BALB/c mice model of cytomegalovirus-induced myocarditis was established. Methods: Twentyfive inbred female BALB/c mice free of murine cytomegalovirus(MCMV) infection (5 weeks old, 16-18 g), were infected with 1 x 104PFU MCMV by the intraperitoneal (i. p. ) administration. All experimental mice were sacrificed on day 3, 5, 7, 10, and 14 after i. p. administration. The hearts were removed under aseptic conditions, and were transected along the midline. Aliquots of hearts were handled with Bouin' s fixative for histological examination. Residual hearts were immediately frozen in liquid nitrogen and stored at - 80℃ until MCMV titre was determined by a plaque assay. Seurm cTnI level was assayed by ELISA. Results: MCMV in the heart was at extremely low level on day 3 after i. p. administration, reached to the peak on day 7-10, and then ran down. A mixed cellular infiltrate composed of polymorphonuclear neutrophils and mononuclear lymphocytes was observed on day 3, reaching to the peak on day 7-10 after MCMV infection, and was maintained for at least 3-4 months later. Seurm cTnI levels were elevated on day 3 after i.p. administration, reaching to the peak it day7-10. Conclusion: The BALB/c mice model for cytomegalovirus-induced myocarditis was successfully established, that might make it possible to screen antiviral drugs for treating viral myocarditis and to investigate and evaluate the pathogenesis and prognosis of this disease.

  11. 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.

  12. 南京市0~8岁儿童巨细胞病毒感染流行病学调查%Seroprevalence of Cytomegalovirus infection in children aged 0-8 years in Nanjing

    Institute of Scientific and Technical Information of China (English)

    吴美玲; 陈洁; 钟天鹰; 周乙华; 胡娅莉

    2013-01-01

    目的 调查儿童巨细胞病毒(CMV)感染率及首次感染的年龄,为了解中国CMV感染现状提供循证医学证据.方法 随机抽取2011年6月至9月在南京市儿童医院体检的837例儿童.男513例,女324例;年龄1d~8岁,平均3.6岁.采用固相ELISA酶联免疫试剂,定性检测体检儿童血清中CMV IgM抗体、定量检测CMV IgG抗体浓度及IgG亲合力指数.结果 837例儿童血清中,CMV IgG阳性690例,阳性率为82.4%.其中男童阳性427例,阳性率83.2%;女童阳性263例,阳性率81.2%,男童与女童CMV IgG阳性率之间差异无统计学意义(x2=0.584,P=0.445).在92例6月龄以内的儿童中,其中86例CMV IgG阳性,阳性率为93.5%;7月龄之后阳性率逐渐下降,在9月龄下降至最低,为66.7%,然后随年龄增长而升至80.0%左右(x2=15.4,P<0.001).从837例儿童中按年龄段随机抽取352例,同时检测其血清CMV IgM,共23例阳性,总IgM阳性率为6.5%,其中以2~3月龄婴儿阳性率最高,达58.3%,之后逐渐下降,6岁以后未检出CMV IgM阳性病例(x2=5.1,P <0.001).进一步检测23例活动性感染标本的IgG抗体亲合力指数,发现13例IgG亲合力指数<30%,原发感染率为56.5%,其中以<1岁儿童居多(7例),占总原发感染数的53.8%.结论 目前南京地区儿童CMV感染率大约为80.0%,低于成人,其首次感染多数发生在3月龄前.%Objective To investigate the seroprevalence of Cytomegalovirus (CMV) infection and ages of the children in primary for better understanding the status of CMV infection in China with evidence-based medicine.Methods Total 837 children randomly selected from Nanjing Children's Hospital,from Jun.to Sep.in 2011,including 513 boys and 324 girls,aged from 1 day to 8 years,with mean age of 3.6 years old,were recruited.Serum samples were tested for CMV IgM,CMV IgG,and CMV IgG avidity index using commercial enzyme-linked immunosorbent assay kits.Results Of the total serum samples from 837

  13. 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.

  14. Human cytomegalovirus induces a distinct innate immune response in the maternal-fetal interface.

    Science.gov (United States)

    Weisblum, Yiska; Panet, Amos; Zakay-Rones, Zichria; Vitenshtein, Alon; Haimov-Kochman, Ronit; Goldman-Wohl, Debra; Oiknine-Djian, Esther; Yamin, Rachel; Meir, Karen; Amsalem, Hagai; Imbar, Tal; Mandelboim, Ofer; Yagel, Simcha; Wolf, Dana G

    2015-11-01

    The initial interplay between human cytomegalovirus (HCMV) and innate tissue response in the human maternal-fetal interface, though crucial for determining the outcome of congenital HCMV infection, has remained unknown. We studied the innate response to HCMV within the milieu of the human decidua, the maternal aspect of the maternal-fetal interface, maintained ex vivo as an integral tissue. HCMV infection triggered a rapid and robust decidual-tissue innate immune response predominated by interferon (IFN)γ and IP-10 induction, dysregulating the decidual cytokine/chemokine environment in a distinctive fashion. The decidual-tissue response was already elicited during viral-tissue contact, and was not affected by neutralizing HCMV antibodies. Of note, IFNγ induction, reflecting immune-cell activation, was distinctive to the maternal decidua, and was not observed in concomitantly-infected placental (fetal) villi. Our studies in a clinically-relevant surrogate human model, provide a novel insight into the first-line decidual tissue response which could affect the outcome of congenital infection.

  15. Human Cytomegalovirus US28 Facilitates Cell-to-Cell Viral Dissemination

    Directory of Open Access Journals (Sweden)

    Vanessa M. Noriega

    2014-03-01

    Full Text Available Human cytomegalovirus (HCMV encodes a number of viral proteins with homology to cellular G protein-coupled receptors (GPCRs. These viral GPCRs, including US27, US28, UL33, and UL78, have been ascribed numerous functions during infection, including activating diverse cellular pathways, binding to immunomodulatory chemokines, and impacting virus dissemination. To investigate the role of US28 during virus infection, two variants of the clinical isolate TB40/E were generated: TB40/E-US28YFP expressing a C-terminal yellow fluorescent protein tag, and TB40/E-FLAGYFP in which a FLAG-YFP cassette replaces the US28 coding region. The TB40/E-US28YFP protein localized as large perinuclear fluorescent structures at late times post-infection in fibroblasts, endothelial, and epithelial cells. Interestingly, US28YFP is a non-glycosylated membrane protein throughout the course of infection. US28 appears to impact cell-to-cell spread of virus, as the DUS28 virus (TB40/E-FLAGYFP generated a log-greater yield of extracellular progeny whose spread could be significantly neutralized in fibroblasts. Most strikingly, in epithelial cells, where dissemination of virus occurs exclusively by the cell-to-cell route, TB40/E-FLAGYFP (DUS28 displayed a significant growth defect. The data demonstrates that HCMV US28 may contribute at a late stage of the viral life cycle to cell-to-cell dissemination of virus.

  16. 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.

  17. Stepwise adaptation of murine cytomegalovirus to cells of a foreign host for identification of host range determinants.

    Science.gov (United States)

    Ostermann, Eleonore; Pawletko, Kerstin; Indenbirken, Daniela; Schumacher, Uwe; Brune, Wolfram

    2015-06-01

    Ever since their first isolation 60 years ago, cytomegaloviruses have been recognized as being highly species specific. They replicate only in cells of their own or a closely related host species, while cells of phylogenetically more distant hosts are usually not permissive for viral replication. For instance, human cytomegalovirus replicates in human and chimpanzee fibroblasts but not in rodent cells, and murine cytomegalovirus (MCMV) replicates in cells of mice and rats but not in primate cells. However, the viral and cellular factors determining the narrow host range of cytomegaloviruses have remained largely unknown. We show that MCMV can be adapted stepwise to replicate in cultured human retinal pigment epithelial (RPE-1) cells and human fibroblasts. The human RPE-1 cells used for the initial adaptation step showed a pronounced contact inhibition and produced very low level of interferon-β transcripts upon cytomegalovirus infection, suggesting that these cells provide a particularly favorable environment for adaptation. By whole genome sequencing of the 230 kbp viral genomes of several adapted mutants, a limited number of mutations were detected. Comparison of several human cell-adapted MCMV clones and introduction of specific mutations into the wild-type MCMV genome by site-directed mutagenesis allows for the identification of viral host range determinants and provides the basis for elucidating the molecular basis of the cytomegalovirus host species specificity.

  18. Murine cytomegalovirus targets transcription factor ATF4 to exploit the unfolded-protein response.

    Science.gov (United States)

    Qian, Zhikang; Xuan, Baoqin; Chapa, Travis J; Gualberto, Nathaniel; Yu, Dong

    2012-06-01

    The unfolded-protein response (UPR), activated by sensor molecules PERK, ATF6, and IRE1 to resolve endoplasmic reticulum (ER) stress, has emerged as a key target for host cells and viruses to control the infection outcomes. The UPR regulates ER protein folding, controls cell fate upon ER stress, and plays an important role in innate immunity. We and others have shown that human cytomegalovirus (HCMV) modulates the UPR. We show here that murine CMV (MCMV), the widely used CMV model for small animal infection, regulated the UPR in a manner similar to that of HCMV. This modulatory ability was triggered by virion entry and enhanced by viral immediate-early and early gene expression. Thus, while vulnerable at early times, MCMV became resistant to exogenous ER stress at late times of infection. MCMV activated the PERK-ATF4 pathway but only induced a subset of representative ATF4 targets at levels somewhat lower than those by the ER stress inducer tunicamycin. Moreover, MCMV induced ER chaperone Bip but actively blocked IRE1-mediated Xbp1(s) protein accumulation. ATF4 depletion severely attenuated viral growth at a low multiplicity of infection by modestly reducing viral DNA synthesis and more pronouncedly inhibiting late gene transcription. Collectively, we show that the UPR is a conserved target of CMVs and identify ATF4, a key UPR component, as a factor critical for MCMV infection. This work sets the stage for using the MCMV model to explore the role of this stress response in CMV biology, particularly during infection of the host, which is difficult to study in HCMV.

  19. 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.

  20. Cytomegalovirus and inflammatory bowel disease: Is there a link?

    Institute of Scientific and Technical Information of China (English)

    Valeria Criscuoli; Maria Rosa Rizzuto; Mario Cottone

    2006-01-01

    The objective of this report is to give an overall view of the epidemiological, clinical, diagnostic and therapeutic features of Cytomegalovirus (CMV) infection in inflammatory bowel disease (IBD). A review of published reports on this topic was carried out, with particular attention paid to the selection of patients included in studies and the diagnostic methods employed. CMV is frequently associated with IBD. In some cases, CMV infection is as sociated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. The use of anti-viral therapy in IBD is controversial and an empirical study with controls is needed. The natural history of CMV infection related to the development and treatment of IBD has not been clarified but it is important to take it in consideration because of the possibility of viral persistence in the immunocompromised host and viral interaction with the immune system.

  1. The Role of Cytomegalovirus in the Development of ARC-AIDS

    Science.gov (United States)

    1991-08-30

    sera, taken in chronological order of receipt into the laboratory, from HLV -1- seropositive subjects, for the presence of antibodies to cellular...CI)4 +T-cell numbers in IIIV-1 infected subjects, but CMV infections appear to be important. The drug DHPG (gancyclovir) has been used in suppressing...CMV drugs that can be given orally. The data we have presented in this paper reinforce the recommendation of DiNubile [37] that in cytomegalovirus

  2. 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.

  3. Cytomegalovirus

    Science.gov (United States)

    ... virus, your doctor may suggest a test called amniocentesis. During this test, a needle is inserted into ... familydoctor.org editorial staff Tags: Allergy and Immunologic, Amniocentesis, child, fever, infant, jaundice, newborn, Throat Pain, weakness ...

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Human cytomegaloviruses expressing yellow fluorescent fusion proteins--characterization and use in antiviral screening.

    Science.gov (United States)

    Straschewski, Sarah; Warmer, Martin; Frascaroli, Giada; Hohenberg, Heinrich; Mertens, Thomas; Winkler, Michael

    2010-02-11

    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.

  9. 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.

  10. Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

    Directory of Open Access Journals (Sweden)

    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.

  11. Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation.

    Directory of Open Access Journals (Sweden)

    Ceri A Fielding

    2014-05-01

    Full Text Available NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC A andB, and UL16-binding proteins (ULBP1-6 induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV have aided both the identification and characterization of NKG2D ligands (NKG2DLs. HCMV immediate early (IE gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12-US21; a genetic arrangement, which is suggestive of an 'accordion' expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US

  12. Characterization of the transcripts of human cytomegalovirus UL144

    Directory of Open Access Journals (Sweden)

    Sun Zhengrong

    2011-06-01

    Full Text Available Abstract Background The genome of human cytomegalovirus (HCMV has been studied extensively, particularly in the UL/b' region. In this study, transcripts of one of the UL/b' genes, UL144, were identified in 3 HCMV isolates obtained from urine samples of congenitally infected infants. Methods Northern blot hybridization, cDNA library screening, and RACE-PCR were used. Results We identified at least 4 differentially regulated 3'-coterminal transcripts of UL144 in infected cells of 1,300, 1,600, 1,700, and 3,500 nucleotides (nt. The 1600 nt transcript was the major form of UL144 mRNA. The largest transcript initiated from the region within the UL141 open reading frame (ORF and included UL141, UL142, UL143, UL144, and UL145 ORFs. Conclusions These findings reveal the complex nature of the transcription of the UL144 gene in clinical isolates.

  13. Knowledge and Awareness of Congenital Cytomegalovirus Among Women

    Directory of Open Access Journals (Sweden)

    Jiyeon Jeon

    2006-01-01

    Full Text Available Background. Congenital cytomegalovirus (CMV infection is a leading cause of disabilities in children, yet the general public appears to have little awareness of CMV. Methods. Women were surveyed about newborn infections at 7 different geographic locations. Results. Of the 643 women surveyed, 142 (22% had heard of congenital CMV. Awareness increased with increasing levels of education (P<.0001. Women who had worked as a healthcare professional had a higher prevalence of awareness of CMV than had other women (56% versus 16%, P <.0001. Women who were aware of CMV were most likely to have heard about it from a healthcare provider (54%, but most could not correctly identify modes of CMV transmission or prevention. Among common causes of birth defects and childhood illnesses, women's awareness of CMV ranked last. Conclusion. Despite its large public health burden, few women had heard of congenital CMV, and even fewer were aware of prevention strategies.

  14. 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

  15. 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.

  16. Human Cytomegalovirus and Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Anne Halenius

    2014-01-01

    Full Text Available Human cytomegalovirus (HCMV represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE, systemic sclerosis (SSc, diabetes mellitus type 1, and rheumatoid arthritis (RA is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.

  17. 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

    BACKGROUND: In the 'USPHS/IDSA Guidelines for Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus', the indications for chemoprophylaxis are based on nadir CD4 cell count. Many patients have, however, experienced an increase in CD4 cell count after....../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...

  18. 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.

  19. Leukotriene B4-mediated release of antimicrobial peptides against cytomegalovirus is BLT1 dependent.

    Science.gov (United States)

    Gaudreault, Eric; Gosselin, Jean

    2007-09-01

    Leukotriene B4 (LTB(4)) is a potent lipid mediator of inflammation that possesses antiviral activities. Here we provide evidence that LTB(4)-mediated defense against in vitro cytomegalovirus (CMV) infection of human leukocytes involves activation of the high-affinity LTB(4) receptor (BLT1) and neutrophil degranulation. Treatment of CMV-infected peripheral blood leukocytes with LTB(4) (10 nM) leads to a significant reduction in viral titers. This activity involves neutrophil activation through the BLT1 receptor, because no reduction in viral titers was observed after neutrophil depletion from cellular preparation or when leukocytes were pretreated with the BLT1 antagonist U75,302. Direct stimulation of neutrophils with LTB(4) (in the presence or absence of CMV) leads to the release of myeloperoxidase, alpha-defensins, eosinophil-derived neurotoxin, and the human cathelicidin LL-37 in a BLT1-dependent manner. LTB(4) does not act exclusively on the secretion of preformed antimicrobial peptides, but also acts on the synthesis of selected peptides as reflected by the increase in transcriptional levels of eosinophil-derived neurotoxin (EDN) and LL-37 in LTB(4)-treated neutrophils. Treatment of cell cultures with neutralizing antibodies directed against alpha-defensins, EDN, and LL-37 significantly reduces the antiviral effect of LTB(4), suggesting that LTB(4) may act through the release of antimicrobial peptides. Ex vivo experiments using LTB(4)-treated neutrophils from peritoneal washing of wild-type and BLT1 knockout mice further supported the role played by antimicrobial peptides in LTB(4)-mediated antiviral activity toward CMV. These results provide evidence of a mechanism by which LTB(4) induces host defense against viral infection.

  20. Physical activity and upper respiratory tract infections.

    Science.gov (United States)

    Kostka, T; Drygas, W; Jegier, A; Praczko, K

    2008-02-01

    We explored the relationship of current and lifetime physical activity (PA) with upper respiratory tract infections (URTI) symptomatology in 142 male volunteers aged 33 to 90. They participated in baseline and one-year follow-up examinations and fulfilled the log books for daily recording of URTI symptomatology during the whole year. PA was assessed by the Seven Day Recall PA Questionnaire and the Historical Leisure Activity Questionnaire. Number of URTI episodes per year and the number of days with URTI per year were significantly inversely associated with the follow-up 7-Day Recall Hard score (rho = - 0.21; p = 0.013 and rho = - 0.18; p = 0.032, respectively). In logistic regression model, after adjustment for age and anthropometric data, the subjects with high follow-up 7-Day Recall Hard score (dichotomised as high vs. low) had a lower probability of having at least 2 URTI episodes per year (OR = 0.38; CI = 0.18 - 0.78), lower probability of having at least 3 URTI episodes per year (OR = 0.42; CI = 0.20 - 0.87), and lower probability of having at least 15 days with URTI (OR = 0.36; CI = 0.15 - 0.88). URTI symptomatology was not related to cardiorespiratory fitness or any measures of the historical PA questionnaire. We conclude that in middle-aged and older men the symptomatology of URTI over long periods of time is inversely related to current but not to lifetime PA.

  1. 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

  2. Cytomegalovirus pneumonia as the first manifestation of severe combined immunodeficiency

    Science.gov (United States)

    Jończyk-Potoczna, Katarzyna; Ossowska, Lidia; Bręborowicz, Anna; Bartkowska-Śniatkowska, Alicja; Wachowiak, Jacek

    2014-01-01

    Severe combined immunodeficiency (SCID) is characterized by the absence of functional T lymphocytes and impairment of adaptive immunity. While heterogeneity of the genetic background in SCID leads to the variability of immune phenotypes, most of affected newborns appear healthy but within the first few months they develop life-threatening opportunistic respiratory or gastrointestinal tract infections. The objective of the study was to define the presenting features and etiology of infections in children with SCID. We retrospectively reviewed five children in whom the diagnosis of SCID had been established in our pediatric immunology clinic over the last 10-year period. A viral respiratory tract infection was the first manifestation of SCID in all the children studied. Cytomegalovirus (CMV) pneumonia was recognized in as many as 4 cases and coronavirus pulmonary infection was diagnosed in one case, whereas Pneumocystis jiroveci was identified as a co-pathogen in one CMV-infected patient. Severe combined immunodeficiency is a pediatric emergency condition and given the significant impact of pulmonary CMV infection in SCID children, establishing an accurate etiological diagnosis is of essential importance in instituting the specific treatment and improving the outcome. PMID:26155153

  3. In Vitro Characterization of Human Cytomegalovirus-Targeting Therapeutic Monoclonal Antibodies LJP538 and LJP539

    Science.gov (United States)

    Patel, Hetalkumar D.; Nikitin, Pavel; Gesner, Thomas; Lin, James J.; Barkan, David T.; Ciferri, Claudio; Carfi, Andrea; Akbarnejad Yazdi, Tahmineh; Skewes-Cox, Peter; Wiedmann, Brigitte; Jarousse, Nadine; Zhong, Weidong; Feire, Adam

    2016-01-01

    Human cytomegalovirus (HCMV) infection is usually benign in healthy individuals but can cause life-threatening disease in those with compromised immune systems. Approved drugs available to treat HCMV disease, including ganciclovir, cidofovir, and foscarnet, have significant toxicities that limit their use in certain patient populations. LJP538 and LJP539 are human monoclonal antibodies that are being evaluated as immunoglobulin therapeutics. The antibodies target glycoproteins gB and the gH/gL/UL128/UL130/UL131a pentameric complex, respectively. Here we present an in vitro characterization of these antibodies. We show that LJP538 and LJP539 are more potent than a marketed immunoglobulin at inhibiting HCMV infection of various cell lines relevant to pathogenesis. We find that LJP538 and LJP539 are active against a panel of clinical isolates in vitro and demonstrate minor-to-moderate synergy in combination. Passage of HCMV in the presence of LJP538 or LJP539 alone resulted in resistance-associated mutations that mapped to the target genes. However, no loss of susceptibility to the combination of antibodies was observed for >400 days in culture. Finally, the binding regions of LJP538 and LJP539 are conserved among clinical isolates. Taken together, these data support the use of LJP538 and LJP539 in combination for clinical trials in HCMV patients. PMID:27270290

  4. Human cytomegalovirus increases HUVEC sensitivity to thrombin and modulates expression of thrombin receptors.

    Science.gov (United States)

    Popović, Milan; Paskas, Svetlana; Zivković, Maja; Burysek, Ladislav; Laumonnier, Yves

    2010-08-01

    Human cytomegalovirus (HCMV) establishes a life-long persistent infection. HCMV infection could be associated with chronic inflammatory diseases, such as cardiovascular disease and atherosclerosis. Here we observed that in HCMV (AD-169) pre-exposed human umbilical vein endothelial cells (HUVEC), thrombin-induced expression of IL-1alpha and M-CSF is markedly enhanced compared to the un-exposed cells. Study of the expression of thrombin receptor genes in HUVEC showed that HCMV triggered a time- and concentration-dependent expression of the thrombin receptors PAR1, PAR3 and PAR4 at the mRNA level. Induction of PAR1 and PAR3 mRNA expression is due to transcriptional activation of their promoters as shown by gene reporter assay. Furthermore, the virus induced expression of PAR1 and PAR3 but not PAR4 proteins, as analyzed by Western immunoblotting. However, flow cytometric analysis revealed that only PAR3, expressed at very low level in control HUVEC, is induced at the surface during the exposure to the virus. Our data suggest that although exposure to HCMV induces a minor increase of cell-surface receptors expression, it does make endothelial cells more responsive to additional thrombin stimulation.

  5. Chitinase Activity in Healthy and Sclerotium rolfsii Infected Peanut

    Directory of Open Access Journals (Sweden)

    ENDANG PUDJIHARTATI

    2006-06-01

    Full Text Available The objectives of this experiment were to analyze the endo- or exo-chitinase activities of healthy and Sclerotium rolfsii infected peanuts. The experiment analyzed 24 different peanut genotypes. Results of the experiment showed chromogenic dimer was the most suitable substrate for analysing chitinase activities. Both endo- and exo-chitinases activities were detected in leaf, stem, and crown tissues. Increased in chitinase activities were detected in S. rolfsii infected peanut tissues than in healthy plant. Regression analysis showed negative slope between disease intensity and chitinase activity in S. rolfsii infected peanut tissue (R2= 0.45.

  6. Diagnosis and Treatment of Cytomegalovirus Keratitis%巨细胞病毒性角膜炎的诊断与治疗

    Institute of Scientific and Technical Information of China (English)

    王玉珏; 朱丹; 陶勇

    2016-01-01

    Cytomegalovirus is widespread in nature, is a high rate of human infection of a virus, it can infringe the human body organs, so that the human body for a long time to carry the virus. In the research of cytomegalovirus, we ifnd the cytomegalovirus can infect cornea, which is called cytomegalovirus keratitis. The clinical features of cytomegalovirus keratitis were corneal edema, Keratic Precipitates (KP), intraocular pressure, repeated infection and corneal endothelial cells decreased. Cytomegalovirus keratitis can be diagnosed by real-time PCR, and this diagnosis can not only diagnose cytomegalovirus infection, but also evaluate the severity of the disease. Currently the prevention and treatment of cytomegalovirus keratitis of drugs, including: ganciclovir and phosphonoformate, cidofovir, poly I-C etc., these drugs in largely improves the doctor of cytomegalovirus infection prevention and control capacity. The diagnosis and treatment of cytomegalovirus keratitis are discussed in this paper.%巨细胞病毒在自然界中广泛存在,是人类感染率极高的一种病毒,它可侵犯人体的各个器官,使人体长期以致终生携带病毒。在对巨细胞病毒的研究中表明巨细胞病毒可感染角膜引起角膜炎症,称巨细胞病毒性角膜炎。巨细胞病毒性角膜炎的临床特征是不同程度的角膜水肿、角膜后沉淀物、高眼压、反复感染和角膜内皮细胞减少。巨细胞病毒性角膜炎可以利用实时定量荧光PCR进行诊断,这种诊断方法不仅可以确诊巨细胞病毒感染,还可评估疾病的严重性。目前预防和治疗巨细胞病毒性角膜炎的药物包括更昔洛韦、膦甲酸、西多福韦、聚肌胞等,这些药物在很大程度上提高了医生对巨细胞病毒感染的防治能力。本文将对巨细胞病毒性角膜炎的诊断与治疗做系统论述。

  7. Cytomegalovirus Reactivation in Adult Recipients of Autologous Stem Cell Transplantation: a Single Center Experience

    OpenAIRE

    Al-Rawi, Omar; Abdel-Rahman, Fawzi; Al-Najjar, Rula; Abu-Jazar, Husam; Salam, Mourad; Saad, Mustafa

    2015-01-01

    Introduction Cytomegalovirus (CMV) reactivation and infection are well-recognized complications after allogeneic stem cell transplantation (SCT). Only a few studies have addressed CMV reactivation after autologous SCT (ASCT). Methods We retrospectively reviewed medical records of 210 adult patients who underwent ASCT for lymphoma or multiple myeloma (MM) at a single center from January 1st, 2007 until December 31st, 2012. All patients were monitored weekly with CMV antigenemia test till day 4...

  8. Intractable Diarrhea from Cytomegalovirus Colitis in a Case with Hereditary Spherocytosis

    Directory of Open Access Journals (Sweden)

    Murat Ozkale

    2015-09-01

    Full Text Available Cytomegalovirus (CMV infection is a common viral infection worldwide, with a frequency as high as 90% in developing countries. Only 10% of primary CMV infection is symptomatic in immunocompetent patients, and it rarely causes specific complications. We report CMV colitis in an immunocompetent adolescent with hereditary spherocytosis and spontaneous rupture of the spleen, who was critically ill with septicemia and significant non-bloody diarrhoea that responded to specific CMV treatment. [Cukurova Med J 2015; 40(3.000: 609-613

  9. 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.

  10. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    Science.gov (United States)

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  11. 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.

  12. Case report: persistent cytomegalovirus (CMV) infection after haploidentical hematopoietic stem cell transplantation using in vivo alemtuzumab: emergence of resistant CMV due to mutations in the UL97 and UL54 genes.

    Science.gov (United States)

    Oshima, Kumi; Kanda, Yoshinobu; Kako, Shinichi; Asano-Mori, Yuki; Watanabe, Takuro; Motokura, Toru; Chiba, Shigeru; Shiraki, Kimiyasu; Kurokawa, Mineo

    2008-10-01

    Addition of in vivo alemtuzumab to the conditioning regimen enabled 2- or 3-locus-mismatched hematopoietic stem cell transplantation with an acceptable incidence of graft-versus-host-disease. However, the procedure was associated with a high incidence of cytomegalovirus (CMV) reactivation. Although preemptive therapy with ganciclovir prevented successfully severe CMV diseases and CMV-related mortality, a patient developed persistent positive CMV antigenemia for more than 1 year after transplantation and CMV disease, despite the use of ganciclovir and foscarnet. The in vitro susceptibility assay showed that the clinical isolate was resistant to foscarnet, moderately resistant to ganciclovir, but sensitive to cidofovir. Therefore, cidofovir was administered. CMV antigenemia became negative within 2 weeks and never developed again. Nucleotide sequence of the UL54 and UL97 of the clinical isolate showed 4 amino acid substitutions (V11L, Q578H, S655L, and G874R) in UL54 and 2 mutations (A140V and A594V) in UL97 compared with the Towne and AD169 strains. Ganciclovir resistance was suspected to be caused by both A594V of UL97 and Q578H of UL54, whereas foscarnet resistance was due mainly to Q578H of UL54. In conclusion, the in vitro susceptibility assay as well as nucleotide sequence of clinical isolate is important to choose appropriate antiviral agents for patients who have persistent CMV reactivation after stem cell transplantation.

  13. Congenital Cytomegalovirus: a "Now" Problem-No Really, Now.

    Science.gov (United States)

    Bernstein, David I

    2017-01-01

    Despite the clear need, progress toward a vaccine for congenital cytomegalovirus (CMV) has been slow. However, recent events have provided new interest, and several vaccine candidates are either in clinical trials or the trials are close to starting. In this issue of Clinical and Vaccine Immunology, Schleiss and colleagues show that a nonreplicating lymphocytic choriomeningitis virus (rLCMV)-vectored vaccine expressing CMV glycoprotein B (gB) and/or pp65 induces B and T cells and improves pup survival in a guinea pig model of congenital CMV infection (Clin Vaccine Immunol 24:e00300-16, 2017, https://doi.org/10.1128/CVI.00300-16). The combination vaccine appeared to be the most effective.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Cytomegalovirus ileocolitis in a rheumatoid arthritis patient: case report and literature review

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. 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.

  1. CC and CX3C chemokines differentially interact with the N terminus of the human cytomegalovirus-encoded US28 receptor

    DEFF Research Database (Denmark)

    Casarosa, Paola; Waldhoer, Maria; LiWang, Patricia J;

    2005-01-01

    , that displays homology to the human chemokine receptor CCR1 and binds several chemokines of the CC family as well as the CX3C chemokine fractalkine with high affinity. Most importantly, following HCMV infection, US28 activates several intracellular pathways, either constitutively or in a chemokine-dependent...... binding to US28, whereas receptor activation depends on the presence of the N terminus of CCL4, as shown previously for CCR5.......Human cytomegalovirus (HCMV) is the causative agent of life-threatening systemic diseases in immunocompromised patients as well as a risk factor for vascular pathologies, like atherosclerosis, in immunocompetent individuals. HCMV encodes a G-protein-coupled receptor (GPCR), referred to as US28...

  2. Incidence and relationship of human cytomegalovirus infection and human herpesvirus 6 infection in pediatric patients after hemopoietic stem cell transplantation%儿童造血干细胞移植患者人巨细胞病毒与疱疹病毒6型感染及相互关系

    Institute of Scientific and Technical Information of China (English)

    吕典一; 秦茂权; 王燕; 高立伟; 谢正德

    2010-01-01

    Objective To study the incidence of human cytomegalovirus (CMV) and human herpesvirus 6(HHV-6) infection in pediatric patients with hemopoietic stem cell transplantation (HSCT),and to explore the relationship between CMV and HHV-6 infection in pediatric patients with HSCT.Methods Pediatric patients with HSCT in hemotology center of Beijing Children's Hospital were enrolled into this study from June 2007 to October 2009. Peripheral blood were collected every week after HSCT, and Fluorescent quantitation PCR and conventional PCR were used to detect CMV DNA load in serum and HHV-6 DNA in peripheral blood respectively. Genetic typing was conducted on HHV-6. Results Fifty two pediatric patients with HSCT were enrolled into this study, and six hundreds and thirty six specimens were collected totally. CMV DNA was detected in fifty two specimens from twenty cases. The median time was 56days after HSCT. The incidence of CMV infection was 38.5% (20/52)in all HSCT patients and 47. 6% (20/42) in allogene HSCT patients. The incidence of late CMV infection was 22.2% (6/27)in allogene HSCT.Three patients died of C MV infection,and two died of CMV interstitial pneumonia. HHV-6 DNA was detected in thirty three specimens from fourteen cases. The median time was 23 days after HSCT. The incidence of HHV-6 infection was 26.9% ( 14/52 ) in all HSCT patients and 31% ( 13/42 ) in allogene HSCT patients. The genotype of HHV6 was all type B. HHV-6 DNA was positive in six of twenty cases with CMV infection. The%目的 了解儿童造血干细胞移植患者术后人巨细胞病毒与疱疹病毒6型的感染情况以及相互关系.方法 患者为2007年6月至2009年10月间北京儿童医院血液病中心的造血干细胞移植的患儿,患儿术后每周采集外周静脉血,分别应用荧光定量PCR和常规PCR检测患者血清中CMV DNA载量及外周全血中HHV-6,并对HHV-6进行分型.结果 共52例造血干细胞移植患者,636份标本.20例造血干细胞移植患者共52

  3. Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages.

    Directory of Open Access Journals (Sweden)

    Aline Cristina Abreu Moreira-Souza

    Full Text Available Infection by the protozoan parasite Toxoplasma gondii is highly prevalent worldwide and may have serious clinical manifestations in immunocompromised patients. T. gondii is an obligate intracellular parasite that infects almost any cell type in mammalian hosts, including immune cells. The immune cells express purinergic P2 receptors in their membrane--subdivided into P2Y and P2X subfamilies--whose activation is important for infection control. Here, we examined the effect of treatment with UTP and UDP in mouse peritoneal macrophages infected with T. gondii tachyzoites. Treatment with these nucleotides reduced parasitic load by 90%, but did not increase the levels of the inflammatory mediators NO and ROS, nor did it modulate host cell death by apoptosis or necrosis. On the other hand, UTP and UDP treatments induced early egress of tachyzoites from infected macrophages, in a Ca2+-dependent manner, as shown by scanning electron microscopy analysis, and videomicroscopy. In subsequent infections, prematurely egressed parasites had reduced infectivity, and could neither replicate nor inhibit the fusion of lysosomes to the parasitophorous vacuole. The use of selective agonists and antagonists of the receptor subtypes P2Y2 and P2Y4 and P2Y6 showed that premature parasite egress may be mediated by the activation of these receptor subtypes. Our results suggest that the activity of P2Y host cell receptors controls T. gondii infection in macrophages, highlighting the importance of pyrimidinergic signaling for innate immune system response against infection. Finally the P2Y receptors should be considered as new target for the development of drugs against T. gondii infection.

  4. Cytomegalovirus oesophagitis in a patient with non-hodgkin′s lymphoma

    Directory of Open Access Journals (Sweden)

    Hingmire S

    2008-01-01

    Full Text Available Cytomegalovirus (CMV infection is frequent in immunocompromised patients, especially in AIDS, organ transplantation and rarely in Hodgkin′s disease and Non-Hodgkin′s lymphoma (NHL. We present a case of NHL with CMV oesophagitis, which has rarely been documented in literature. Apart from fungal and herpes simplex infections, as the common differential diagnosis for oesophagitis in patients of lymphoma, CMV should be considered an important etiologic agent. Early diagnosis and prompt treatment of CMV oesophagitis with gancyclovir can avert significant morbidity and avoid unacceptable treatment delays.

  5. Molecular and Biological Characterization of a New Isolate of Guinea Pig Cytomegalovirus

    Directory of Open Access Journals (Sweden)

    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.

  6. Highly quantitative serological detection of anti-cytomegalovirus (CMV antibodies

    Directory of Open Access Journals (Sweden)

    Alter Harvey J

    2009-05-01

    Full Text Available Abstract Background Human cytomegalovirus infection is associated with a variety of pathological conditions including retinitis, pneumonia, hepatitis and encephalitis that may be transmitted congenitally, horizontally and parenterally and occurs both as a primary infection and as reactivation in immunocompromised individuals. Currently, there is a need for improved quantitative serological tests to document seropositivity with high sensitivity and specificity. Methods Here we investigated whether luciferase immunoprecipitation systems (LIPS would provide a more quantitative and sensitive method for detecting anti-CMV antibodies. Four protein fragments of immunodominant regions of CMV antigens pp150 and pp65 were generated as Renilla luciferase (Ruc fusion proteins and used in LIPS with two cohorts of CMV positive and negative sera samples previously tested by ELISA. Results Analysis of the antibody responses to two of these antigen fragments, pp150-d1 and pp150-d2, revealed geometric mean antibody titers in the first cohort that were 100–1000 fold higher in the CMV positive sera compared to the CMV negative samples (p rs = 0.93, p Conclusion These results suggest that LIPS provides a highly robust and quantitative method for studying anti-CMV antibodies and has the potential to more accurately document CMV infection than standard ELISA.

  7. 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.

  8. Mayaro virus infection cycle relies on casein kinase 2 activity.

    Science.gov (United States)

    Barroso, Madalena M S; Lima, Carla S; Silva-Neto, Mário A C; Da Poian, Andrea T

    2002-09-06

    Replication of Mayaro virus in Vero cells induces dramatic cytopathic effects and cell death. In this study, we have evaluated the role of casein kinase 2 (CK2) during Mayaro virus infection cycle. We found that CK2 was activated during the initial stages of infection ( approximately 36% after 4h). This activation was further confirmed when the enzyme was partially purified from the cellular lysate either by Mono Q 5/5Hr column or heparin-agarose column. Using this later column, we found that the elution profile of CK2 activity from infected cells was different from that obtained for control cell enzyme, suggesting a structural modification of CK2 after infection. Treatment of infected cells with a cell-permeable inhibitor of CK2, dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DRB), abolished the cytopathic effect in a dose-dependent manner. Together this set of data demonstrates for the first time that CK2 activity in host cells is required in Mayaro virus infection cycle.

  9. Experimental Study of Prevention and Therapeutic Effect of Jinyebaidu Granules on Cytomegalovirus Infection During Mid-pregnancy%金叶败毒颗粒防治妊娠中期巨细胞病毒宫内感染的实验研究

    Institute of Scientific and Technical Information of China (English)

    李伟; 陈素华; 熊锦文; 陈娟娟; 刘涛; 肖娟; 刘静; 张艳丽; 冯云; 曾雪

    2015-01-01

    目的:观察金叶败毒颗粒防治妊娠中期豚鼠巨细胞病毒宫内感染的效果。方法选择无感染史性、成熟期雌雄豚鼠同笼受精,随机选择妊娠中期母豚鼠分为3组,每组15只,正常对照组无特殊处理,模型对照组腹腔接种病毒,金叶败毒组接种病毒同时灌胃给予金叶败毒颗粒(3.09 mL· kg-1),7 d后观察各组母豚鼠病毒血症发生率,20 d后观察各组胎盘感染率、胎仔感染率及死胎率。结果正常对照组和模型对照组死胎率分别为8.33%,34.55%( P<0.05)。模型对照组和金叶败毒组亲代感染率分别为86.67%,33.33%;胎盘感染率分别为91.67%,61.22%;胎仔感染率分别为90.91%,48.28%;死胎率分别为34.55%,15.52%(均P<0.05)。结论金叶败毒颗粒可减少妊娠中期病毒接种引起的母胎感染及胎仔死亡,减少胎盘感染。%Objective To study the effect of Jingyebaidu granules on treating cytomegalovirus ( CMV) infection during mid-pregnancy. Methods The sexually mature guinea pigs with no CMV infection history served as the subjects. Put the male and female ones in the same cages. Then the female ones were randomly divided into three groups during mid-pregnancy. Model control group:15 guinea pigs which were inoculated 1 mL suspension of GPCMV intraperitoneally. Jingyebaidu Medicine group:15 guinea pigs which were treated with Jingyebaidu(3. 09 mL·kg-1 ) through stomach perfusion after inoculation for 14 days. Normal control group:15 normal mid-pregnant guinea pigs. Viremia rates were examined 7 days after infection. All animals were sacrificed 20 days after infection. The placenta infection rate, pup infection rate, still-born rate were examined. Results Compared with the normal controls, the still-born rate was increased in model control group(8. 33% vs 34. 55%, P<0. 05). In comparison to the model control group, the GPCMV maternal infection rate(86. 67% vs 33. 33%), placenta infection rate (91. 67% vs 61. 22%), pup infection

  10. 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

    2016-01-01

    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

  11. Platelet activation determines the severity of thrombocytopenia in dengue infection

    Science.gov (United States)

    Ojha, Amrita; Nandi, Dipika; Batra, Harish; Singhal, Rashi; Annarapu, Gowtham K.; Bhattacharyya, Sankar; Seth, Tulika; Dar, Lalit; Medigeshi, Guruprasad R.; Vrati, Sudhanshu; Vikram, Naval K.; Guchhait, Prasenjit

    2017-01-01

    Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections. PMID:28139770

  12. 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.

  13. Multiple host kinases contribute to Akt activation during Salmonella infection.

    Science.gov (United States)

    Roppenser, Bernhard; Kwon, Hyunwoo; Canadien, Veronica; Xu, Risheng; Devreotes, Peter N; Grinstein, Sergio; Brumell, John H

    2013-01-01

    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.

  14. 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.

  15. Coincident helminth infection modulates systemic inflammation and immune activation in active pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    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.

  16. The oncogenic potential of human cytomegalovirus and breast cancer.

    Directory of Open Access Journals (Sweden)

    Georges eHerbein

    2014-08-01

    Full Text Available Breast cancer is among the leading causes of cancer-related death among women. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. Numerous articles indicate that breast tumors exhibit diverse phenotypes depending on their distinct physiopathological signatures, clinical courses and therapeutic possibilities. The human cytomegalovirus (HCMV is a multifaceted highly host specific betaherpesvirus that is regarded as asymptomatic or mildly pathogenic virus in immunocompetent host. HCMV may cause serious in utero infections as well as acute and chronic complications in immunocompromised individual. The involvement of HCMV in late inflammatory complications underscores its possible role in inflammatory diseases and cancer. HCMV targets a variety of cell types in vivo, including macrophages, epithelial cells, endothelial cells, fibroblasts, stromal cells, neuronal cells, smooth muscle cells, and hepatocytes. HCMV can be detected in the milk after delivery and thereby HCMV could spread to adjacent mammary epithelial cells. HCMV also infects macrophages and induces an atypical M1/M2 phenotype, close to the tumor associated macrophage phenotype, which is associated with the release of cytokines involved in cancer initiation or promotion and breast cancer of poor prognosis. HCMV antigens and DNA have been detected in tissue biopsies of breast cancers and elevation in serum HCMV IgG antibody levels has been reported to precede the development of breast cancer in some women. In this review, we will discuss the potential role of HCMV in the initiation and progression of breast cancer.

  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

    Directory of Open Access Journals (Sweden)

    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. Inner ear infections as cause of perinatal deafness

    Directory of Open Access Journals (Sweden)

    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.

  19. Multiple lymphoid nodules in bone marrow biopsy in immunocompetent patient with cytomegalovirus infection: an immunohistochemical analysis Múltiplos nódulos linfóides na medula óssea de paciente imunocompetente com infecção pelo citomegalovirus: uma análise imunohistoquímica

    Directory of Open Access Journals (Sweden)

    Silvia Maria Meire Magalhães

    2001-01-01

    Full Text Available In Brazil, a high prevalence of cytomegalovirus (CMV infection has been documented. In immunocompetent adults CMV infection is usually asymptomatic and therefore morphologic and immunophenotypic bone marrow changes have rarely been described. The authors report the case of a previously healthy patient who developed fever of undetermined origin. The diagnosis of acute CMV infection was based on serological testing. A computed tomographic scan showed mediastinal lymphadenopathy. A bone marrow biopsy revealed a hypercellular haematopoiesis with eosinophilia and large mixed T- and B-cell lymphoid aggregates. In spite of bcl-2 positivity, their reactive nature was demonstrated. Polymerase chain reaction (PCR and immunohistochemistry were unable to detect CMV-DNA in paraffin-embedded bone marrow sections. Much like in other systemic disorders, the lymphoid nodules in this case seemed to be caused by immunological mechanisms, possibly due to cytokines released in response to the systemic infectious process.Uma elevada prevalência de infecção pelo citomegalovírus (CMV está documentada no Brasil. Em adultos imunocompetentes a infecção pelo CMV é, em geral, assintomática e, portanto, as alterações morfológicas e imunohistoquímicas na medula óssea têm sido raramente descritas. Relatamos o caso de um paciente previamente assintomático que desenvolveu febre de origem obscura. O diagnóstico de infecção aguda pelo CMV foi baseado em estudo sorológico. A tomografia computadorizada do tórax mostrou linfadenopatia mediastinal. A biópsia óssea revelou medula hipercelular com eosinofilia e grandes agregados linfóides mistos de células B e T. Apesar da positividade para bcl-2, a sua natureza reacional foi demostrada. A reação em cadeia da polimerase (PCR e a imunohistoquímica não detectaram DNA viral nos cortes de medula óssea em parafina. Assim como em outros distúrbios sistêmicos, os nódulos linfóides no nosso caso parecem ser

  20. 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.

  1. Diagnostic value of enzyme linked immuno-sorbent assay for cytomegalovirus disease.

    Directory of Open Access Journals (Sweden)

    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.

  2. Activation of an NLRP3 inflammasome restricts Mycobacterium kansasii infection.

    Directory of Open Access Journals (Sweden)

    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.

  3. Optimal management of cytomegalovirus retinitis in patients with AIDS

    Directory of Open Access Journals (Sweden)

    Michael W Stewart

    2010-04-01

    Full Text Available Michael W StewartDepartment of Ophthalmology, Mayo School of Medicine, Jacksonville, FL, USAAbstract: Cytomegalovirus (CMV retinitis is the most common cause of vision loss in patients with acquired immunodeficiency syndrome (AIDS. CMV retinitis afflicted 25% to 42% of AIDS patients in the pre-highly active antiretroviral therapy (HAART era, with most vision loss due to macula-involving retinitis or retinal detachment. The introduction of HAART significantly decreased the incidence and severity of CMV retinitis. Optimal treatment of CMV retinitis requires a thorough evaluation of the patient’s immune status and an accurate classification of the retinal lesions. When retinitis is diagnosed, HAART therapy should be started or improved, and anti-CMV therapy with oral valganciclovir, intravenous ganciclovir, foscarnet, or cidofovir should be administered. Selected patients, especially those with zone 1 retinitis, may receive intravitreal drug injections or surgical implantation of a sustained-release ganciclovir reservoir. Effective anti-CMV therapy coupled with HAART significantly decreases the incidence of vision loss and improves patient survival. Immune recovery uveitis and retinal detachments are important causes of moderate to severe loss of vision. Compared with the early years of the AIDS epidemic, the treatment emphasis in the post-HAART era has changed from short-term control of retinitis to long-term preservation of vision. Developing countries face shortages of health care professionals and inadequate supplies of anti-CMV and anti-HIV medications. Intravitreal ganciclovir injections may be the most cost effective strategy to treat CMV retinitis in these areas.Keywords: cytomegalovirus, AIDS, retinitis, immune recovery uveitis, retinal detachment, treatment

  4. 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.

  5. [Seroprevalence of rubella virus, varicella zoster virus, cytomegalovirus and parvovirus B19 among pregnant women in the Sousse region, Tunisia].

    Science.gov (United States)

    Hannachi, N; Marzouk, M; Harrabi, I; Ferjani, A; Ksouri, Z; Ghannem, H; Khairi, H; Hidar, S; Boukadida, J

    2011-02-01

    The aim of the study is to evaluate seroprevalence of rubella virus (RV), cytomegalovirus (CMV), varicella zoster virus (VZV), and parvovirus B19 (PB19) in 404 Tunisian pregnant women, and to determine reliability of maternal past history of eruption. Sociodemographic characteristics, risk factors, and past history of eruption were collected through a questionnaire. Serologic tests were performed using enzyme immunoassays. Risk factors were analyzed using univariate and multivariate logistic regression models. Seroprevalences were 79.7% for rubella, 96.3% for CMV, 80.9% for VZV, and 76.2% for PB19. In multivariate analysis, the number of persons per room (> 2) in the house during childhood was associated with CMV infection (P = 0.004), irregular professional husband's activity was correlated with VZV infection (P = 0.04), and an age of more than 30 years was associated with PB19 infection (P = 0.02). History of rubella, varicella, and PB19 infection was unknown for, respectively, 55.8%, 20%, and 100% of women. False history of rubella and varicella were found for 7.4% and 15% of women, respectively. The positive and negative predictive values (PPV and NPV) of rubella history were, respectively, 92.6% and 17.2%, and were, respectively, 84.9% and 20.9% for varicella history. Susceptibility to RV, VZV, and PB19 infection remains high in pregnancy in our population. Preventive strategies against congenital rubella must be reinforced. Vaccination against VZV should be considered in seronegative women. Systemic CMV screening is not warranted in our country where high immunity is acquired probably in childhood. Since maternal history of eruption is not reliable, we recommend serologic testing to determine immune status of women.

  6. Cytomegalovirus induces abnormal chondrogenesis and osteogenesis during embryonic mandibular development

    Directory of Open Access Journals (Sweden)

    Bringas Pablo

    2008-03-01

    Full Text Available Abstract Background Human clinical studies and mouse models clearly demonstrate that cytomegalovirus (CMV disrupts normal organ and tissue development. Although CMV is one of the most common causes of major birth defects in humans, little is presently known about the mechanism(s underlying CMV-induced congenital malformations. Our prior studies have demonstrated that CMV infection of first branchial arch derivatives (salivary glands and teeth induced severely abnormal phenotypes and that CMV has a particular tropism for neural crest-derived mesenchyme (NCM. Since early embryos are barely susceptible to CMV infection, and the extant evidence suggests that the differentiation program needs to be well underway for embryonic tissues to be susceptible to viral infection and viral-induced pathology, the aim of this study was to determine if first branchial arch NCM cells are susceptible to mCMV infection prior to differentiation of NCM derivatives. Results E11 mouse mandibular processes (MANs were infected with mouse CMV (mCMV for up to 16 days in vitro. mCMV infection of undifferentiated embryonic mouse MANs induced micrognathia consequent to decreased Meckel's cartilage chondrogenesis and mandibular osteogenesis. Specifically, mCMV infection resulted in aberrant stromal cellularity, a smaller, misshapen Meckel's cartilage, and mandibular bone and condylar dysmorphogenesis. Analysis of viral distribution indicates that mCMV primarily infects NCM cells and derivatives. Initial localization studies indicate that mCMV infection changed the cell-specific expression of FN, NF-κB2, RelA, RelB, and Shh and Smad7 proteins. Conclusion Our results indicate that mCMV dysregulation of key signaling pathways in primarily NCM cells and their derivatives severely disrupts mandibular morphogenesis and skeletogenesis. The pathogenesis appears to be centered around the canonical and noncanonical NF-κB pathways, and there is unusual juxtaposition of abnormal stromal

  7. Human cytomegalovirus chemokine receptor US28 induces migration of cells on a CX3CL1-presenting surface

    DEFF Research Database (Denmark)

    Hjortø, Gertrud M; Kiilerich-Pedersen, Katrine; Selmeczi, David

    2013-01-01

    Human cytomegalovirus (HCMV)-encoded G protein-coupled-receptor US28 is believed to participate in virus dissemination through modulation of cell migration and immune evasion. US28 binds different CC chemokines and the CX3C chemokine CX3CL1. Membrane-anchored CX3CL1 is expressed by immune......-activated endothelial cells, causing redirection of CX3CR1-expressing leukocytes in the blood to sites of infection. Here, we used stable transfected cell lines to examine how US28 expression affects cell migration on immobilized full-length CX3CL1, to model how HCMV-infected leukocytes interact with inflamed...... endothelium. We observed that US28-expressing cells migrated more than CX3CR1-expressing cells when adhering to immobilized CX3CL1. US28-induced migration was G protein-signalling dependent and was blocked by the phospholipase Cβ inhibitor U73122 and the intracellular calcium chelator BAPTA-AM. In addition...

  8. 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.

  9. Disseminated rhodococcus equi infection in HIV infection despite highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    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.

  10. Celulitis por citomegalovirus Cytomegalovirus cellulitis

    Directory of Open Access Journals (Sweden)

    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

  11. 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

  12. Activation of Natural Killer cells during microbial infections

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. Direct and Indirect Effects of Cytomegalovirus-induced gamma-delta T Cells after Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    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

  15. Cytomegalovirus Restructures Lipid Rafts via a US28/CDC42-Mediated Pathway, Enhancing Cholesterol Efflux from Host Cells

    OpenAIRE

    2016-01-01

    Cytomegalovirus (HCMV) contains cholesterol, but how HCMV interacts with host cholesterol metabolism is unknown. We found that, in human fibroblasts, HCMV infection increased the efflux of cellular cholesterol, despite reducing the abundance of ABCA1. Mechanistically, viral protein US28 was acting through CDC42, rearranging actin microfilaments, causing association of actin with lipid rafts, and leading to a dramatic change in the abundance and/or structure of lipid rafts. These changes displ...

  16. Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune activation.

    Science.gov (United States)

    Inglis, Fiona M; Lee, Kim M; Chiu, Kevin B; Purcell, Olivia M; Didier, Peter J; Russell-Lodrigue, Kasi; Weaver, Scott C; Roy, Chad J; MacLean, Andrew G

    2016-04-01

    Chikungunya, "that which bends up" in the Makonde dialect, is an emerging global health threat, with increasing incidence of neurological complications. Until 2013, Chikungunya infection had been largely restricted to East Africa and the Indian Ocean, with cases within the USA reported to be from foreign travel. However, in 2014, over 1 million suspected cases were reported in the Americas, and a recently infected human could serve as an unwitting reservoir for the virus resulting in an epidemic in the continental USA. Chikungunya infection is increasingly being associated with neurological sequelae. In this study, we sought to understand the role of astrocytes in the neuropathogenesis of Chikungunya infection. Even after virus has been cleared form the circulation, astrocytes were activated with regard to TLR2 expression. In addition, white matter astrocytes were hypertrophic, with increased arbor volume in gray matter astrocytes. Combined, these would alter the number and distribution of synapses that each astrocyte would be capable of forming. These results provide the first evidence that Chikungunya infection induces morphometric and innate immune activation of astrocytes in vivo. Perturbed glia-neuron signaling could be a major driving factor in the development of Chikungunya-associated neuropathology.

  17. False dual infection of Epstein-Barr virus and cytomegalovirus in children with infectious mononucleosis%假性EBV和CMV双重感染的传染性单核细胞增多症的临床特点

    Institute of Scientific and Technical Information of China (English)

    王云峰

    2014-01-01

    目的 探讨假性EB病毒(EBV)和巨细胞病毒(CMV)双重感染的传染性单核细胞增多症(IM)的临床特点,以及通过临床特点早期识别假性双重感染的临床意义.方法 回顾性总结13例CMV-IgM假阳性的由EBV导致IM的临床特点,并将该病例组与确诊的单纯EBV感染导致的IM病例、已证实由EBV和CMV双重感染导致的IM病例分别比较.结果 ①各组间临床特点比较:发热持续时间、肝肿大及脾肿大的发生率病例组与单纯EBV感染组间差异无统计学意义(均P>0.05),但这些异常在该二组显著低于双重感染组(P<0.05或P<0.01).IM并发症,如贫血和肺炎的发生率,病例组与单纯EBV感染组间差异无统计学意义(P>0.05),但该二组的发生率显著低于双重感染组(P <0.05或P<0.01);②各组间实验室指标比较:异型淋巴细胞百分比和肝功能异常的发生率,病例组与单纯EBV感染组间无统计学差异(P>0.05),但该二组显著低于双重感染组(P<0.05或P<0.01).结论 某些IM病例早期存在CMV-IgM假阳性的情况,确诊依赖于针对EBV和CMV的抗体的动态检测.EBV和CMV双重感染者常临床症状较重,故可通过临床症状早期识别假性EBV和CMV双重感染.%Objective The aim of this study was to explore the characteristics of children with IM suspected for false dual infection of EBV/CMV and the early identification of false positive CMV-IgM through the characteristics of IM.Method The characteristics of 13 patients with IM suspected for the false dual infection of EBV/CMV were retrospectively analyzed and compared with the EBV infection cases and the confirmed dual infection cases of EBV and CMV,respectively.Results ① Clinical manifestations:there were no statistical significance of the duration of fever and the incidence of hepatomegaly and splenomegaly between the false dual infection group and the EBV infection group (P > 0.05),but the anomalies in these two groups were

  18. Spontaneous neutrophil activation in HTLV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Jaqueline B. Guerreiro

    2005-12-01

    Full Text Available Human T cell lymphotropic Virus type-1 (HTLV-1 induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy; 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS-stimulated neutrophil activity (reduction of NBT to formazan. The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001 in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24% and 17±4.8% respectively (p< 0.001, while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20%. Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

  19. 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.

  20. 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

  1. Report from the second cytomegalovirus and immunosenescence workshop.

    Science.gov (United States)

    Wills, Mark; Akbar, Arne; Beswick, Mark; Bosch, Jos A; Caruso, Calogero; Colonna-Romano, Giuseppina; Dutta, Ambarish; Franceschi, Claudio; Fulop, Tamas; Gkrania-Klotsas, Effrossyni; Goronzy, Joerg; Griffiths, Stephen J; Henson, Sian; Herndler-Brandstetter, Dietmar; Hill, Ann; Kern, Florian; Klenerman, Paul; Macallan, Derek; Macualay, Richard; Maier, Andrea B; Mason, Gavin; Melzer, David; Morgan, Matthew; Moss, Paul; Nikolich-Zugich, Janko; Pachnio, Annette; Riddell, Natalie; Roberts, Ryan; Sansoni, Paolo; Sauce, Delphine; Sinclair, John; Solana, Rafael; Strindhall, Jan; Trzonkowski, Piotr; van Lier, Rene; Vescovini, Rosanna; Wang, George; Westendorp, Rudi; Pawelec, Graham

    2011-10-28

    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.

  2. Report from the second cytomegalovirus and immunosenescence workshop

    Directory of Open Access Journals (Sweden)

    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.

  3. Canadian society of transplantation consensus workshop on cytomegalovirus management in solid organ transplantation final report.

    Science.gov (United States)

    Preiksaitis, Jutta K; Brennan, Daniel C; Fishman, Jay; Allen, Upton

    2005-02-01

    The Canadian Society of Transplantation sponsored a Cytomegalovirus (CMV) Consensus Working Group that met on March 19, 2003. The objectives of this group were to determine the current burden of CMV-associated disease in the setting of solid organ transplantation in Canada, make recommendations regarding optimal strategies for the diagnosis, treatment and prevention of CMV infection and disease, highlight gaps in knowledge and outline priorities for research and other initiatives that might further reduce the burden of CMV-associated effects in this setting. This report summarizes the recommendations of the working group including ratings of the strength of evidence supporting the recommendations.

  4. Roles of host and viral microRNAs in human cytomegalovirus biology

    OpenAIRE

    Dhuruvasan, Kavitha; Sivasubramanian, Geetha; Pellett, Philip E.

    2010-01-01

    Human cytomegalovirus (HCMV) has a relatively large and complex genome, a protracted lytic replication cycle, and employs a strategy of replicational latency as part of its lifelong persistence in the infected host. An important form of gene regulation in plants and animals revolves around a type of small RNA known as microRNA (miRNA). miRNAs can serve as major regulators of key developmental pathways, as well as provide subtle forms of regulatory control. The human genome encodes over 900 mi...

  5. Low predictive value of polymerase chain reaction for diagnosis of cytomegalovirus disease in liver transplant recipients.

    Science.gov (United States)

    Delgado, R; Lumbreras, C; Alba, C; Pedraza, M A; Otero, J R; Gómez, R; Moreno, E; Noriega, A R; Payá, C V

    1992-07-01

    The polymerase chain reaction (PCR) and viral culture techniques were prospectively compared for the detection of cytomegalovirus (CMV) in blood samples from 24 liver transplant recipients. Nine patients had one or more episodes of viremia, seven of which were clinically symptomatic infections. All samples in which CMV was isolated by culture were positive by the PCR. However, the PCR result was also positive for one or more samples from 11 patients who never developed CMV-related symptoms. Although the PCR is a very sensitive technique for CMV detection in blood samples from liver transplant recipients, it is not useful as a marker of symptomatic CMV disease.

  6. The level of C.pneumoniae, Cytomegalovirus, and H.pylori antibody in a patient with coronary heart disease

    Directory of Open Access Journals (Sweden)

    Dasnan Ismail

    2002-12-01

    Full Text Available At herosclerosis is still the chief cause of morbidity and mortality in developed nations. Even though in developed nations the modification of risk factors is able to reduce the prevalence rate of atherosclerosis, such reduction is starting to slow down. Such condition has stimulated researchers to identify environmental exposure, including infection, that can influence the process of atherosclerosis. This cross sectional study was conducted from March to August 1998, on 122 patients that clinically demonstrate coronary heart disease and have underwent cardiac catheterization, 92 males and 30 females with an average age of 55 years. Patients undergo clinical and laboratory evaluation (blood glucose, cholesterol, triglyceride, and antibody for C.pneumoniae. Cytomegalovirus, and H.pylori. We found a significant difference in cholesterol, triglyceride, and HDL levels in those with coronary stenosis and those without. However, we did not find a significant difference in the levels of C.pneumoniae, Cytomegalovirus, and H.pylori antibodies. This study is unable to conclude the influence of these antibodies on atherosclerosis, since in the non-stenosis group, we cannot eliminate the possibility of atherosclerosis, since the average age of study subject is 55 years. Studies on the interaction between infection and traditional risk factors as well as gender and nutrition is needed to find a clear answer of the influence of infection in atherosclerosis. (Med J Indones 2002; 11: 211-4Keywords: Level of C.pneumoniae, Cytomegalovirus, H.pylori antibody, coronary heart disease.

  7. 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.

  8. Marine peptides and their anti-infective activities.

    Science.gov (United States)

    Kang, Hee Kyoung; Seo, Chang Ho; Park, Yoonkyung

    2015-01-16

    Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, and antiviral activities. In the last several decades, studies of marine plants, animals, and microbes have revealed tremendous number of structurally diverse and bioactive secondary metabolites. However, the treatments available for many infectious diseases caused by bacteria, fungi, and viruses are limited. Thus, the identification of novel antimicrobial peptides should be continued, and all possible strategies should be explored. In this review, we will present the structures and anti-infective activity of peptides isolated from marine sources (sponges, algae, bacteria, fungi and fish) from 2006 to the present.

  9. Marine Peptides and Their Anti-Infective Activities

    Directory of Open Access Journals (Sweden)

    Hee Kyoung Kang

    2015-01-01

    Full Text Available Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, and antiviral activities. In the last several decades, studies of marine plants, animals, and microbes have revealed tremendous number of structurally diverse and bioactive secondary metabolites. However, the treatments available for many infectious diseases caused by bacteria, fungi, and viruses are limited. Thus, the identification of novel antimicrobial peptides should be continued, and all possible strategies should be explored. In this review, we will present the structures and anti-infective activity of peptides isolated from marine sources (sponges, algae, bacteria, fungi and fish from 2006 to the present.

  10. Influence of congenital asymptonmtic cytomegalovirus infection on development of infants%先天性无症状性巨细胞病毒感染对婴儿期发育的影响

    Institute of Scientific and Technical Information of China (English)

    单若冰; 王晓亮; 傅平

    2008-01-01

    目的 通过对先天性无症状性巨细胞病毒(HCMV)感染的新生儿进行系统随访,观察其听力学、体格发育、智能发育、行为发育等多方面的改变,探讨先天性无症状性HCMV感染对婴儿期发育的影响.方法 按照1998年宜昌会议通过的标准及美国Fowler标准确定先天性无症状性巨细胞病毒感染.2003年7月至2005年7月符合人选条件感染病例41例,对照组21例.进行静脉血荧光定量PCR(FQ-PcR)检测确定HCMV感染.感染组与对照组于新生儿期、3月龄、6月龄、1岁分别进行新生儿20项行为神经检查(NBNA)、听力学检查包括耳声发射听力检查(OAE)、听力脑干诱发电位检查(ABR)、Bayley婴幼儿发育量表评估发育智商、52项运动神经检查(Amid-Tison法)和体格发育检查、一般状况检查.结果 (1)两组新生儿12~14 d时加项NBNA得分分别为38.8±2.75和38.5±2.29,差异无统计学意义(t=0.98,P>0.05).(2)ABR检查:感染组中23例做ABR检查者V波阈值升高异常率为15.2%;对照组21例未发现V波阈值升高,差异有统计学意义,所有病例均通过OAE检查.(3)感染组中38例1岁时行Bayley婴幼儿发育量表检查智力发育指数(MDI)及精神运动发育指数(PDI)分别为106.86±10.24和108.45±18.25,与对照组2l例(107.49±19.31和107.19±10.98)差异亦无统计学意义(t=0.33,P>0.05,t=0.35,P>0.05).(4)52项运动神经发育:两组比较,差异无统计学意义(t=0.02,P>0.05).结论 (1)先天性无症状HCMV感染在婴儿期即可出现脑干听性反应V波阈值升高,而OAE听力筛查未能检出异常.(2)先天性无症状性HCMV感染对新生儿期行为神经、婴儿期智力、婴儿期神经运动发育无明显影响.%Objective Human cytomegalovims(HCMV)is a ubiquitous human-specific DNA virus and is the main cause of congenital virus infection worldwide.Although 90% of the congenitally infected infants are clinically asymptomatic at birth.evidences show that these

  11. Cytotoxic T lymphocyte activity in children infected with HIV.

    Science.gov (United States)

    Froebel, K S; Aldhous, M C; Mok, J Y; Hayley, J; Arnott, M; Peutherer, J F

    1994-01-01

    Of the Edinburgh cohort of approximately 130 children born to HIV-infected women, 9 are infected and alive. This article describes results from the first 18 months of a natural history study of seven of these, and two adopted children, studying the CD8 T cell-mediated cytotoxicity against HIV proteins (Gag, Tat, Pol, and Env), over time, and relating it to clinical progression and viral activity. Autologous EBV cell lines infected with vaccinia-HIV constructs were used as target cells, and bulk-cultured peripheral blood mononuclear cells as effector cells. The children ranged in age from 0 to 93 months, with six of the nine showing CTL activity to one or more HIV proteins. The specificity of the response was directed against Tat in the younger children, switching to Pol, then Gag or Env. Preliminary analysis of virological data showed no association between CTL and virus activity. The children with CTLs tended to be well clinically, but the cohort needs to be studied longer before conclusions can be made about CTL activity and HIV disease progression. Cytotoxic T lymphocyte activity has also been observed in two children diagnosed as HIV uninfected. These results show the importance of looking at CTL specificity, and may have implications in vaccine design.

  12. A temporal gate for viral enhancers to co-opt Toll-like-receptor transcriptional activation pathways upon acute infection.

    Science.gov (United States)

    Kropp, Kai A; Hsieh, Wei Yuan; Isern, Elena; Forster, Thorsten; Krause, Eva; Brune, Wolfram; Angulo, Ana; Ghazal, Peter

    2015-04-01

    Viral engagement with macrophages activates Toll-Like-Receptors (TLRs) and viruses must contend with the ensuing inflammatory responses to successfully complete their replication cycle. To date, known counter-strategies involve the use of viral-encoded proteins that often employ mimicry mechanisms to block or redirect the host response to benefit the virus. Whether viral regulatory DNA sequences provide an opportunistic strategy by which viral enhancer elements functionally mimic innate immune enhancers is unknown. Here we find that host innate immune genes and the prototypical viral enhancer of cytomegalovirus (CMV) have comparable expression kinetics, and positively respond to common TLR agonists. In macrophages but not fibroblasts we show that activation of NFκB at immediate-early times of infection is independent of virion-associated protein, M45. We find upon virus infection or transfection of viral genomic DNA the TLR-agonist treatment results in significant enhancement of the virus transcription-replication cycle. In macrophage time-course infection experiments we demonstrate that TLR-agonist stimulation of the viral enhancer and replication cycle is strictly delimited by a temporal gate with a determined half-maximal time for enhancer-activation of 6 h; after which TLR-activation blocks the viral transcription-replication cycle. By performing a systematic siRNA screen of 149 innate immune regulatory factors we identify not only anticipated anti-viral and pro-viral contributions but also new factors involved in the CMV transcription-replication cycle. We identify a central convergent NFκB-SP1-RXR-IRF axis downstream of TLR-signalling. Activation of the RXR component potentiated direct and indirect TLR-induced activation of CMV transcription-replication cycle; whereas chromatin binding experiments using wild-type and enhancer-deletion virus revealed IRF3 and 5 as new pro-viral host transcription factor interactions with the CMV enhancer in macrophages. In a

  13. A temporal gate for viral enhancers to co-opt Toll-like-receptor transcriptional activation pathways upon acute infection.

    Directory of Open Access Journals (Sweden)

    Kai A Kropp

    2015-04-01

    Full Text Available Viral engagement with macrophages activates Toll-Like-Receptors (TLRs and viruses must contend with the ensuing inflammatory responses to successfully complete their replication cycle. To date, known counter-strategies involve the use of viral-encoded proteins that often employ mimicry mechanisms to block or redirect the host response to benefit the virus. Whether viral regulatory DNA sequences provide an opportunistic strategy by which viral enhancer elements functionally mimic innate immune enhancers is unknown. Here we find that host innate immune genes and the prototypical viral enhancer of cytomegalovirus (CMV have comparable expression kinetics, and positively respond to common TLR agonists. In macrophages but not fibroblasts we show that activation of NFκB at immediate-early times of infection is independent of virion-associated protein, M45. We find upon virus infection or transfection of viral genomic DNA the TLR-agonist treatment results in significant enhancement of the virus transcription-replication cycle. In macrophage time-course infection experiments we demonstrate that TLR-agonist stimulation of the viral enhancer and replication cycle is strictly delimited by a temporal gate with a determined half-maximal time for enhancer-activation of 6 h; after which TLR-activation blocks the viral transcription-replication cycle. By performing a systematic siRNA screen of 149 innate immune regulatory factors we identify not only anticipated anti-viral and pro-viral contributions but also new factors involved in the CMV transcription-replication cycle. We identify a central convergent NFκB-SP1-RXR-IRF axis downstream of TLR-signalling. Activation of the RXR component potentiated direct and indirect TLR-induced activation of CMV transcription-replication cycle; whereas chromatin binding experiments using wild-type and enhancer-deletion virus revealed IRF3 and 5 as new pro-viral host transcription factor interactions with the CMV enhancer in

  14. Calpains mediate the proteolytic modification of human cytomegalovirus UL112-113 proteins.

    Science.gov (United States)

    Wang, Shang-Kwei; Jiang, Meei Jyh; Lin, Shin-Rung; Chen, Mei-Yin; Wang, Hung-Hsueh; Duh, Chang-Yih

    2015-05-01

    The human cytomegalovirus (HCMV) UL112-113 gene is implicated in lytic viral replication. The UL112-113 proteins p34, p43, p50 and p84 are expressed via alternative splicing. However, the mechanism for the generation of three additional virus-associated proteins (p20, p26 and p28), which share the UL112 reading frame, remains unknown. Bioinformatic analyses indicated that p34, p43, p50 and p84 contain potential PEST-like degradation motifs. In this study, inhibitors of calpains, lysosomes and proteasomes reduced p20, p26 and p28 levels in virus-infected cells, suggesting the involvement of proteolytic modification. Moreover, maitotoxin, which increases intracellular calcium levels and activates calpain activity, induced the intracellular proteolysis of p34 into p20, p26 and p28 and the cleavage of p43, p50 and p84 into p38 and a novel protein, p34c. Proteolytic assays further indicated that p34, p43, p50 and p84 were substrates of calpain-1 and calpain-2 and that they generated proteolytic products that corresponded to those detected during the HCMV infectious period. Furthermore, substitution mutations in the putative calpain cleavage sites of p34 reduced accumulation of proteolytic products. The knockdown of endogenous calpain-1 and calpain-2 by RNA interference reduced accumulation of p20, p26 and p28 and concurrently increased levels of nascent p43, p50 and p84 during the infectious cycle. Intriguingly, calpain depletion enhanced viral genome synthesis. Moreover, HCMV-permissive cells that stably expressed p20, p26 or p28 exhibited reduced viral genome synthesis and mature virus production. Our findings suggest that cognate UL112-113 proteins derived from calpain-catalysed proteolysis are involved in the HCMV replication process.

  15. 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.

  16. Herpesvirus infections in xenotransplantation: pathogenesis and approaches.

    Science.gov (United States)

    Mueller, Nicolas J; Fishman, Jay A

    2004-11-01

    Infectious risk remains an important consideration in the clinical application of xenotransplantation. Vascularized xenografts create unique immunological niches in which bidirectional transmission of pathogens between donor and recipient may occur. Enhanced replication of many pathogens is stimulated by the immune responses induced by transplantation and by the immune suppression used to prevent graft rejection. Herpesviruses are the prototype viruses that are activated during immunosuppression. Quantitative diagnostic molecular assays have been developed for the known herpesviruses causing infection in pigs. Recent data suggest that some herpesviral infections, such as porcine cytomegalovirus, may be excluded from swine used as source animals by careful breeding, while others will require novel strategies for control. This review focuses on porcine and baboon herpesviruses in pig-to-non-human primate solid organ xenotransplantation including direct effects (tissue damage), indirect effects (coagulopathy, rejection), and possible approaches to these infections.

  17. Insertion and deletion mutagenesis of the human cytomegalovirus genome

    Energy Technology Data Exchange (ETDEWEB)

    Spaete, R.R.; Mocarski, E.S.

    1987-10-01

    Studies on human cytomegalovirus (CMV) have been limited by a paucity of molecular genetic techniques available for manipulating the viral genome. The authors have developed methods for site-specific insertion and deletion mutagenesis of CMV utilizing a modified Escherichia coli lacZ gene as a genetic marker. The lacZ gene was placed under the control of the major ..beta.. gene regulatory signals and inserted into the viral genome by homologous recombination, disrupting one of two copies of this ..beta.. gene within the L-component repeats of CMV DNA. They observed high-level expression of ..beta..-galactosidase by the recombinant in a temporally authentic manner, with levels of this enzyme approaching 1% of total protein in infected cells. Thus, CMV is an efficient vector for high-level expression of foreign gene products in human cells. Using back selection of lacZ-deficient virus in the presence of the chromogenic substrate 5-bromo-4-chloro-3-indolyl ..beta..-D-galactoside, they generated random endpoint deletion mutants. Analysis of these mutant revealed that CMV DNA sequences flanking the insert had been removed, thereby establishing this approach as a means of determining whether sequences flanking a lacZ insertion are dispensable for viral growth. In an initial test of the methods, they have shown that 7800 base pairs of one copy of L-component repeat sequences can be deleted without affecting viral growth in human fibroblasts.

  18. 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.

  19. 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.

  20. Cytomegalovirus and Epstein-Barr virus in breast cancer.

    Science.gov (United States)

    Richardson, Ann K; Currie, Margaret J; Robinson, Bridget A; Morrin, Helen; Phung, Yen; Pearson, John F; Anderson, Trevor P; Potter, John D; Walker, Logan C

    2015-01-01

    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. 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.

  2. 人类巨细胞病毒感染对血管平滑肌细胞脂代谢相关基因表达的影响%Research on influence of human cytomegalovirus infection on expression of vascular smooth muscle cell lipid metabolism-related gene

    Institute of Scientific and Technical Information of China (English)

    谢明英; 李景苏

    2014-01-01

    Objective To investigate the change of intracellular cholesterol lipid metabolism and related gene expression after vascular smooth muscle cells infection by human cytomegalovirus(HCMV).Methods By separating the primary umbilical artery vascular smooth muscle cells with a multiplicity of infection of HCMV attack as the experimental group and the control group a-dopted the DMEM/F12 medium containing 3% bovine serum for simulating infection.The change of cholesterol content in the smooth muscle cells after virus attack was detected and the gene expression gene was detected by the gene expression profiling chip method.Results After vascular smooth muscle cells were infected by HCMV,the intracellular gene expression changed significant-ly,in which low-density lipoprotein receptor-related protein 10,11,12 and HMG-CoA synthase,HMG-CoA reductase and B scaven-ger receptor were upregulated.Apolipoprotein A1 and apolipoprotein M were downregulated.Conclusion HCMV infecting vascular smooth muscle cells may alter the lipid metabolism pathway related gene expression,enhance intracellular cholesterol synthesis,re-sult in the cholesterol metabolism imbalance,thus participate in the pathogenesis process of atherosclerosis.%目的:探讨血管平滑肌细胞被感染人类巨细胞病毒后,其细胞内胆固醇脂代谢及相关基因表达的变化情况。方法通过分离原代脐动脉血管平滑肌细胞,以1个感染复数的人类巨细胞病毒攻击作为实验组,对照组则采用含3%小牛血清的DMEM/F12培养基模拟感染。检测平滑肌细胞内胆固醇含量在病毒攻击后的变化情况,以基因表达谱芯片技术检测基因表达情况。结果血管平滑肌细胞被感染人类巨细胞病毒后,细胞内相关基因表达发生显著变化,其中低密度脂蛋白受体相关蛋白10、11、12以及 HMG-CoA 合成酶,HMG-CoA 还原酶,B 型清道夫受体表达上调。载脂蛋白 A1、载脂蛋白 M 表达下调。结

  3. 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.

  4. Innate immune recognition and activation during HIV infection

    Directory of Open Access Journals (Sweden)

    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.

  5. Innate immune activation in primary HIV-1 infection.

    Science.gov (United States)

    Chang, J Judy; Altfeld, Marcus

    2010-10-15

    There is growing evidence that highlights the role of the immune response during acute human immunodeficiency virus type 1 (HIV-1) infection in the control or development of disease. The adaptive immune responses do not appear until after HIV-1 infection is already well established, so the role of earlier and faster-responding innate immunity needs to be more closely scrutinized. In particular, 2 aspects of innate immunity for which there are growing research developments will be examined in this review: the actions of type I interferons and natural killer cells. These two components of the innate immune response contribute to viral control both by killing infected cells and by modulating other immune cells that develop. However, the role of interferon α in immune activation is a double-edged sword, causing recruitment of adaptive immune cells that can assist in viral control but concurrently contributing to immune activation-dependent disease progression. Understanding the complexity of how innate responses affect the outcome of HIV-1 infection will help in the development of vaccines that can use innate immunity to enhance viral control with minimal pathogenesis.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 2-octynoic acid inhibits hepatitis C virus infection through activation of AMP-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Darong Yang

    Full Text Available Many chronic hepatitis C virus (HCV-infected patients with current therapy do not clear the virus. It is necessary to find novel treatments. The effect of 2-octynoic acid (2-OA on HCV infection in human hepatocytes was examined. The mechanism of 2-OA antiviral activity was explored. Our data showed that 2-OA abrogated lipid accumulation in HCV replicon cells and virus-infected hepatocytes. It suppressed HCV RNA replication and infectious virus production with no cytotoxicity to the host cells. 2-OA did not affect hepatitis B virus replication in HepG2.2.15 cells derived from HepG2 cells transfected with full genome of HBV. Further study demonstrated that 2-OA activated AMP-activated protein kinase (AMPK and inhibited acetyl-CoA carboxylase in viral-infected cells. Compound C, a specific inhibitor of AMPK, inhibited AMPK activity and reversed the reduction of intracellular lipid accumulation and the antiviral effect of 2-OA. Knockdown of AMPK expression by RNA interference abolished the activation of AMPK by 2-OA and blocked 2-OA antiviral activity. Interestingly, 2-OA induced interferon-stimulated genes (ISGs and inhibited microRNA-122 (miR-122 expression in virus-infected hepatocytes. MiR-122 overexpression reversed the antiviral effect of 2-OA. Furthermore, knockdown of AMPK expression reversed both the induction of ISGs and suppression of miR-122 by 2-OA, implying that activated AMPK induces the intracellular innate response through the induction of ISGs and inhibiting miR-122 expression. 2-OA inhibits HCV infection through regulation of innate immune response by activated AMPK. These findings reveal a novel mechanism by which active AMPK inhibits HCV infection. 2-OA and its derivatives hold promise for novel drug development for chronic hepatitis C.

  11. 新生儿巨细胞病毒感染的胞外体二肽基肽酶Ⅳ及血清中白细胞介素-6,-8水平的研究%Levels of Dipeptidyl Peptidase Ⅳ and Interleukin-6,-8 in Neonates of Cytomegalovirus Infection

    Institute of Scientific and Technical Information of China (English)

    李晓莺; 卢宪梅; 阎贝贝; 胡晓燕

    2012-01-01

    Objective To study the levels of dipeptidyl peptidase Ⅳ (DPPⅣ)of exosome(EXO) and interleukin(IL)-6,-8 in serum of neonates with cytomegalovirus(CMV) infection,to investigate the influence of CMV on neonates' immune function,and the roles of DPPⅣ,and IL-6,-8 in serum which played in the process of CMV infection.Methods From January 2008 to December 2010,a total of 53 neonates with CMV infection were collected as CMV group,meanwhile the other 52 non-CMV infection neonates were recruited as control group.By ELASA method to detect the levels of EXO-DPPⅣ and IL-6,-8 in serum,then analysis the differences between two groups.Informed consent was obtained from the parents of each participating neonate.There had no significant difference between two groups among gender,age,gestational age etc.(P>0.05).Results The levels of EXO-DPPⅣ,and IL-6,-8 in serum in CMV group were much higher than those in control group,and had significance difference (P<0.05).Conclusions CMV can break normal immune balance,leading abnormality of enzymes and cytokine.There is close correlation between inflammatory reaction,DPPⅣ,and IL-6,-8.%目的 探讨巨细胞病毒(CMV)感染对新生儿免疫功能的影响及胞外体(EXO)二肽基肽酶Ⅳ(DPPⅣ,CD26)及血清白细胞介素(IL)-6,-8水平在CMV感染发生发展过程中的作用.方法 选择2008年1月至2010年12月山东大学齐鲁医院儿科收治的53例CMV感染新生儿为研究对象,纳入CMV组,选择同期入院的42例非CMV感染新生儿(CMV IgM呈阴性,血、尿中CMV-DNA< 103拷贝/mL)纳入对照组.采用ELASA法检测EXO-DPPⅣ活性及血清IL-6,-8水平,并进行相关统计学分析(本研究遵循的程序符合山东大学齐鲁医院人体试验委员会制定的伦理学标准,得到该委员会批准,分组征得受试对象监护人的知情同意,并与其签署临床研究知情同意书).两组新生儿的性别、年龄及胎龄等比较,差异无统计学意义(P>0.05).结果 CMV组

  12. Cytomegalovirus colitis in a patient with Behcet's disease receiving tumor necrosis factor alpha inhibitory treatment

    Institute of Scientific and Technical Information of China (English)

    Ismail Sari; Merih Birlik; Can Gonen; Server Akar; Duygu Gurel; Fatos Onen; Nurullah Akkoc

    2008-01-01

    Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term safety of these agents. We present a case of a young male Behcet's patient whose disease was complicated by cytomegalovirus (CMV) colitis. Colitis started 10 d after the third Infliximab dose and responded to the cessation of TNF blocking treatment and administration of ganciclovir. Tumor necrosis factor alpha and interferon gamma act at several levels in combating viral infections.CMV infections should be kept in mind and included in the differential diagnosis of severe gastrointestinal symptoms in patients receiving anti-TNF agents.

  13. The effect of human cytomegalovirus on the formation of CFU-MK in vitro.

    Science.gov (United States)

    Yao, Junxia; Song, Sanjun; Hu, Lihua

    2004-01-01

    To investigate the mechanism and the suppressive effect of human cytomegalovirus (HCMV) on colony forming unit-megakaryocyte (CFU-MK), semi-solid culture system was used to observe the effect of HCMV AD169 strain on CFU-MK's growth of 18 cord blood samples. HCMV DNA and immediate early (IE) protein mRNA in CFU-MK was detected by PCR and reverse transcription-polymerase chain reaction (RT-PCR). Our results showed that HCMV AD169 significantly suppressed the formation of CFU-MK in vitro. Compared with the mock group, the CFU-MK colonies decreased by 21.6%, 33.8% and 46.3%, respectively, in all the 3 infected groups (PCFU-MK by directly infecting their progenitors. There was early transcription of HCMV IE protein in CFU-MK infected by virus.

  14. The history of vaccination against cytomegalovirus.

    Science.gov (United States)

    Plotkin, Stanley

    2015-06-01

    Cytomegalovirus vaccine development started in the 1970s with attenuated strains. In the 1980s, one of the strains was shown to be safe and effective in renal transplant patients. Then, attention switched to glycoprotein gB, which was shown to give moderate but transient protection against acquisition of the virus by women. The identification of the pp65 tegument protein as the principal target of cellular immune responses resulted in new approaches, particularly DNA, plasmids to protect hematogenous stem cell recipients. The subsequent discovery of the pentameric protein complex that generates most neutralizing antibodies led to efforts to incorporate that complex into vaccines. At this point, there are many candidate CMV vaccines, including live recombinants, replication-defective virus, DNA plasmids, soluble pentameric proteins, peptides, virus-like particles and vectored envelope proteins.

  15. Macrophage Activation by Ursolic and Oleanolic Acids during Mycobacterial Infection

    Directory of Open Access Journals (Sweden)

    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.

  16. 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 part