RESUMO
Kidney transplanted patients still have significantly higher mortality compared with the general population. The innate immune system may play an important role during periods, with suppression of the adaptive immune system. In the present study, two soluble pattern recognition molecules of the innate immune system were investigated, collectin liver 1 (CL-L1) and collectin kidney 1 (CL-K1). Potential associations of their pretransplant levels and long-term graft and recipient survival were examined. The levels of CL-L1 and CL-K1 were measured at the time of transplantation in 382 patients (≥17 years) transplanted in 2000-2001. The cohort was subsequently followed until December 31, 2014. Data on patient and graft survival were obtained from the Norwegian Renal Registry. Both high CL-L1 (≥376 ng/mL) and high CL-K1 (≥304 ng/mL) levels were significantly associated with overall mortality in multivariate Cox analyses with hazard ration (HR) 1.50, 95% confidence interval (CI) 1.09-2.07, p = 0.013 and HR 1.43, 95% CI 1.02-1.99, p = 0.038, respectively. Moreover, high CL-K1 levels were significantly associated with cardiovascular mortality. No association between measured biomarkers and death-censored graft loss was found. Finally, there was a significant correlation between these two collectins, r = 0.83 (95% CI 0.80-0.86). In conclusion, CL-L1 and CL-K1 were significantly associated with mortality in kidney transplant recipients.
Assuntos
Doenças Cardiovasculares/mortalidade , Colectinas/metabolismo , Rejeição de Enxerto/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Lectina de Ligação a Manose da Via do Complemento , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Lactente , Testes de Função Renal , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
Cytomegalovirus (CMV) encodes multiple microRNAs. While these have been partially characterized in vitro, their relevance to clinical CMV infection has not been evaluated. We analyzed samples from a cohort of solid organ transplant patients with CMV disease (n = 245) for viral microRNA expression. Several CMV microRNAs were readily detectable in patients with CMV disease in variable relative abundance. Expression level generally correlated with DNA viral load and the absence of viral microRNA was associated with faster viral clearance. Detection of hcmv-miR-UL22A-5p at baseline independently predicted the recurrence of CMV viremia upon discontinuation of antiviral therapy (OR 3.024, 95% CI: 1.35-6.8; p = 0.007). A combination of direct mRNA targeting by the microRNA and indirect modulation of gene expression involving isoforms of the transcriptional regulator C-MYC may be responsible for the broad effects seen in the association of gene transcripts with the RNA-induced silencing complex and in global protein expression upon hcmv-miR-UL22A-5p transfection. This novel study of in vivo viral microRNA expression profiles provides unique insight into the complexity of clinical CMV infection following transplantation. We provide evidence that viral microRNAs may have complex effects on gene expression and be associated with specific virologic and clinical outcomes, and thus could be further evaluated as biomarkers.
Assuntos
Infecções por Citomegalovirus/genética , Citomegalovirus/genética , Perfilação da Expressão Gênica , Regulação Viral da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , MicroRNAs/genética , Transplante de Órgãos , Biomarcadores , Western Blotting , Estudos de Coortes , Biologia Computacional , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/virologia , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoprecipitação , MicroRNAs/sangue , Prognóstico , RNA Viral/sangue , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Recidiva , Fatores de Risco , Replicação ViralRESUMO
We evaluated secreted wingless (Wnt) modulators during cytomegalovirus (CMV) infection in solid organ transplant recipients (SOTr). The major findings were: (i) Plasma levels of Dickkopf-1 (DKK-1) were significantly lower in patients with CMV DNAemia above lower level of quantification at baseline. (ii) Receiver operating characteristic analysis indicated that low DKK-1 and increased secreted frizzled related protein-3 levels were predictors of poor virological outcomes during follow-up. Our findings demonstrate an imbalanced pattern of circulating secreted Wnt modulators in SOTr with poor virological outcomes following treatment for CMV disease, and may suggest a role for dysregulated Wnt signaling on viral pathogenesis during CMV infection.
Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Transplante de Órgãos , Proteínas/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Adulto , Infecções por Citomegalovirus/sangue , DNA Viral/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Via de Sinalização Wnt/fisiologiaRESUMO
Patients with common variable immunodeficiency (CVID) have reduced numbers and frequencies of dendritic cells (DCs) in blood, and there is also evidence for defective activation through Toll-like receptors (TLRs). Collectively, these observations may point to a primary defect in the generation of functional DCs. Here, we measured frequencies of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in peripheral blood of 26 CVID patients and 16 healthy controls. The results show that the patients have reduced absolute counts of both subsets. However, the decreased numbers in peripheral blood were not reflected in reduced frequencies of CD34(+) pDC progenitors in the bone marrow. Moreover, studies at the single cell level showed that DCs from CVID patients and healthy controls produced similar amounts of interferon-α or interleukin-12 and expressed similar levels of activation markers in response to human cytomegalovirus and ligands for TLR-7 and TLR-9. The study represents the most thorough functional characterization to date, and the first to assess bone marrow progenitor output, of naturally occurring DCs in CVID. In conclusion, it seems unlikely that CVID is secondary to insufficient production of naturally occurring DCs or a defect in their signalling through TLR-7 or TLR-9.
Assuntos
Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Receptor 7 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Adulto , Contagem de Células Sanguíneas , Células da Medula Óssea/metabolismo , Estudos de Casos e Controles , Citomegalovirus/imunologia , Feminino , Antígenos HLA-DR/metabolismo , Humanos , Imidazóis/metabolismo , Ligante Coestimulador de Linfócitos T Induzíveis/metabolismo , Intestino Delgado/citologia , Intestino Delgado/metabolismo , Selectina L/metabolismo , Ligantes , Masculino , Pessoa de Meia-Idade , Receptores CCR7/metabolismo , Baço/citologia , Baço/metabolismo , Células-Tronco/metabolismoRESUMO
BACKGROUND: Cytomegalovirus (CMV) displays genetic polymorphisms in multiple genes, which may result in important virulence differences. Glycoprotein N (gN) and immediate early 1 (IE1) are key viral genes and immune targets. We aimed to characterize the molecular epidemiology of gN and IE1 genotypes in organ transplant patients with CMV disease in the context of clinical and virologic endpoints. METHODS: A total of 240 patients with CMV disease had genotyping analysis by nested polymerase chain reaction assays and sequencing using blood samples obtained at disease onset. Results were correlated with viral clearance kinetics and recurrence. RESULTS: Complex patterns of gN and IE1 genotypes were present with no clear genetic linkages. No single genotype of IE1 or gN was associated with poorer outcome. For example, different gN or IE1 genotypes had comparable baseline viral load, clearance half-lives, time to clearance, and rates of virologic recurrence. Mixed infection was present at IE1 in 15.8% and gN in 21.9%, but analysis of a single gene was insufficient to detect all mixed infections. Infections caused by multiple strains, as opposed to single strains, were associated with higher baseline viral loads (P = 0.011), delayed viral clearance (P = 0.033), and higher rates of virologic recurrence (P = 0.008). CONCLUSIONS: Genetic diversity in CMV is complex. Specific gN or IE subtypes do not seem to affect in vivo viral virulence patterns in single-strain infections. Mixed infections demonstrate associations with virologic outcomes that single-strain infections do not.
Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/genética , Variação Genética , Transplante de Órgãos/efeitos adversos , Adulto , Antivirais/uso terapêutico , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/etiologia , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Genótipo , Saúde Global , Humanos , Epidemiologia Molecular , Valganciclovir , Carga ViralRESUMO
BACKGROUND: We investigated whether elevation in serum cytomegalovirus (CMV) or Epstein-Barr virus (EBV) immunoglobulin G (IgG) antibody levels precedes the development of breast cancer. METHODS: A nested case-control study was carried out within the Janus Serum Bank cohort. Two serum samples, one taken at least 4 years before diagnosis (sample 2) and an earlier sample (sample 1) from 399 women with invasive breast cancer and from 399 controls, matched for date of blood samples and age were tested for CMV and EBV IgG antibodies. Odds ratios (ORs) with 95% confidence intervals (CIs) for CMV and EBV seroconversion between the samples and unit changes in IgG optical density (OD) examined as a continuous variable were calculated using conditional logistic regression. RESULTS: Eleven cases and three controls seroconverted for CMV IgG between the first and second blood samples, with an adjusted OR for CMV IgG seroconversion of 4.0 (95% CI=1.1-14.4). The risk of breast cancer, adjusted for parity, increased per unit difference in CMV OD between samples (OR=1.7, 95% CI=1.1-2.5). In an analysis restricted to parous cases and age-matched parous controls, the OR for CMV seroconversion for IgG between the two samples, adjusted for parity and age at first birth, was 9.7 (95% CI=1.2-77.3). The EBV seroconversion or change in EBV OD was not associated with risk of breast cancer. CONCLUSION: Our hypothesis that elevation in serum CMV IgG antibody levels precedes the development of breast cancer in some women is supported by the results of this study. Changes in EBV IgG antibody are not associated with risk of breast cancer.
Assuntos
Neoplasias da Mama/epidemiologia , Carcinoma/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Vírus Epstein-Barr/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/complicações , Neoplasias da Mama/virologia , Carcinoma/sangue , Carcinoma/complicações , Carcinoma/virologia , Estudos de Casos e Controles , Citomegalovirus/imunologia , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Feminino , Herpesvirus Humano 4/imunologia , Humanos , Imunoglobulina G/análise , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Paridade , Gravidez , Testes Sorológicos , Adulto JovemRESUMO
An effective host immune response, critical for successful control of Cytomegalovirus (CMV) disease in solid organ transplant recipients, is affected by intensity and type of immunosuppressive therapy. We used information prospectively captured in the VICTOR-trial to investigate the impact of immunosuppressive therapy on short- and long-term outcomes of CMV treatment in organ transplant recipients. Dual, as compared to triple, immunosuppressive therapy ([odds ratios] OR of 2.55; 95% CI: 1.51-4.60; p = 0.002), lower blood concentrations of calcineurin inhibitors (OR of 5.53; CI: 1.04-29.35; p = 0.045), and longer time since transplantation (OR of 1.70; CI: 1.01-2.87; p = 0.047) all showed better early (Day 21) CMV DNAemia eradication. We observed no effect of the intensity of the immunosuppressive therapy on overall rates of viral eradication or recurrence. The type of calcineurin inhibitor (tacrolimus/cyclosporine) or use of mycophenolate did not affect treatment efficacy, although both tacrolimus and mycophenolate treated patients showed a lower rate of virological recurrence OR 0.51 (95% CI: 0.26-0.98; p = 0.044) and OR 0.45 (95% CI: 0.22-0.93; p = 0.031), respectively. Lower total intensity of immunosuppressive therapy was associated with more effective early, but not overall, CMV DNAemia eradication by valganciclovir/ganciclovir therapy. Both mycophenolate and tacrolimus (rather than cyclosporine) therapy seem to be associated with reduced risk of recurrence.
Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/análogos & derivados , Terapia de Imunossupressão/métodos , Adulto , Inibidores de Calcineurina , Ciclosporina/uso terapêutico , DNA Viral/sangue , Feminino , Ganciclovir/administração & dosagem , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Transplante de Órgãos/métodos , Prevenção Secundária , Tacrolimo/uso terapêutico , Resultado do Tratamento , ValganciclovirRESUMO
PURPOSE: To determine whether cytomegalovirus is causally associated with breast cancer and whether cytomegalovirus should be categorised as an oncogenic virus. METHODS: We undertook a review of published epidemiological and laboratory studies, using established causal criteria: Bradford Hill criteria to determine whether cytomegalovirus is associated with breast cancer; and Evans/Mueller criteria to determine whether cytomegalovirus should be categorised as an oncogenic virus. RESULTS: Although there are inconsistencies in the findings of published epidemiological and laboratory studies, these may be explained by factors such as: differences in timing of blood samples, differences in selection of cases and controls, or high cytomegalovirus seroprevalence among participants in the epidemiological studies; and, in the laboratory studies, differences in sample preparations, age of sample, whether or not paired breast cancer and normal breast tissue samples were used, differences in the tests, primers and/or antibodies used, differences in histological types of breast cancer studied, and/or features of the virus. CONCLUSIONS: Overall, the results of published studies of cytomegalovirus and breast cancer suggest cytomegalovirus is a causal factor for at least some types of breast cancer. If the evidence for a link between cytomegalovirus and breast cancer continues to strengthen, further research could lead to: targeted screening; therapy using antiviral drugs; and, perhaps, primary prevention of a significant proportion of breast cancer. Vaccination against viruses has already been shown to be effective in preventing cervix and liver cancer; cytomegalovirus vaccines are already under development.
Assuntos
Neoplasias da Mama/virologia , Citomegalovirus/isolamento & purificação , Animais , Neoplasias da Mama/etiologia , Citomegalovirus/genética , Citomegalovirus/imunologia , Feminino , Humanos , CamundongosRESUMO
The effect of herpesvirus co-infections (HHV-6, HHV-7) on cytomegalovirus (CMV) disease and its response to therapy is unknown. We prospectively analyzed herpesvirus co-infections in transplant recipients with CMV disease. All patients received 3 weeks of antiviral therapy. Samples were collected at baseline (day 0) and then day 3, 7, 14 and 21 poststart of therapy. Viral load testing for CMV, HHV-6 and HHV-7 was done using quantitative PCR assays in 302 patients of whom 256 had documented symptomatic CMV viremia. In this subset, day 0 HHV-6 co-infection was present in 23/253 (9.1%) and HHV-7 in 17/253 (6.7%). Including those positive at any time point raised the prevalence to 79/256 (30.9%) for HHV-6 and 75/256 (29.3%) for HHV-7. Viral co-infection did not influence the response of CMV disease to antiviral therapy. Baseline CMV viral loads, time to eradication and risk of recurrence were similar in patients with and without HHV-6 or HHV-7 co-infection. Ganciclovir and valganciclovir had no clear effect on HHV-6 and HHV-7 viremia. In conclusion, herpesvirus co-infections are common in patients with CMV disease but with standard antiviral therapy, no clear clinical effects are discernable. Routine monitoring for viral co-infection in patients with CMV disease is not indicated.
Assuntos
Infecções por Citomegalovirus/complicações , Citomegalovirus/isolamento & purificação , Herpesvirus Humano 6/isolamento & purificação , Herpesvirus Humano 7/isolamento & purificação , Complicações Pós-Operatórias/virologia , Infecções por Roseolovirus/complicações , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Estudos de Coortes , Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , DNA Viral/genética , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Humanos , Incidência , Agências Internacionais , Pessoa de Meia-Idade , Transplante de Órgãos , Reação em Cadeia da Polimerase , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Infecções por Roseolovirus/virologia , Resultado do Tratamento , Valganciclovir , Carga Viral , Adulto JovemRESUMO
Though an important cause of morbidity and mortality in solid organ transplantation (SOT), the long-term outcomes of cytomegalovirus (CMV) disease treatment have not been well studied. In a randomized trial, 321 SOT recipients with CMV disease were followed 1 year after treatment with either twice daily intravenous ganciclovir or oral valganciclovir (for 21 days) followed by once daily valganciclovir until day 49 in all patients. Clinical and viral eradication of CMV disease was similar between groups. Clinical recurrence beyond day 49 was found in 15.1% and virological recurrence in 30.0%, no difference between groups (p > 0.77). In a multivariable logistic regression analysis, the only independent predictor for recurrence was failure to eradicate DNAemia by day 21 (clinical: OR 3.9 [1.3-11.3], p = 0.012; virological: OR 5.6 [2.5-12.6], p < 0.0001). Eight patients developed ganciclovir resistance, with no difference between groups (p = 0.62). Twenty patients (valganciclovir: 11, ganciclovir: 9, p = 0.82) died, 12 due to infections, two involving CMV disease. There were no differences in long-term outcomes between treatment arms, further supporting the use of oral valganciclovir for treatment of CMV disease. Persistent DNAemia at day 21, CMV IgG serostatus and development of resistance may be relevant factors for further individualization of treatment.
Assuntos
Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Transplante de Órgãos/efeitos adversos , Adulto , Anticorpos Antivirais/sangue , Antivirais/uso terapêutico , Citomegalovirus/imunologia , Resistência a Medicamentos/efeitos dos fármacos , Resistência a Medicamentos/fisiologia , Etnicidade , Feminino , Ganciclovir/administração & dosagem , Humanos , Imunoglobulina G/sangue , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Resultado do Tratamento , Valganciclovir , Carga Viral , Viremia/tratamento farmacológicoRESUMO
Human cytomegalovirus (HCMV) infection is the single most frequent infectious complication in the early period after kidney transplantation. The HCMV load in blood, measured by HCMV PCR or the HCMV pp65 antigen test, is a predictor of HCMV disease in seropositive recipients. However, plasma virus load measurements are of only modest value in predicting the risk of HCMV disease in seronegative recipients of kidneys from seropositive donors. HCMV infection is an independent risk-factor for acute kidney graft rejection. There is also evidence that HCMV is associated with an increased long-term mortality and post-transplant diabetes mellitus. Whether pre-emptive or prophylactic therapy should be the preferred strategy is not yet decided. Some studies indicate that HCMV prophylaxis may reduce the risk of acute rejection, and thereby increase long-term graft survival in seronegative recipients of kidneys from seropositive donors.
Assuntos
Infecções por Citomegalovirus , Transplante de Rim , Complicações Pós-Operatórias , Antivirais/uso terapêutico , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Fosfoproteínas/sangue , Valor Preditivo dos Testes , Fatores de Risco , Carga Viral , Proteínas da Matriz Viral/sangue , ViremiaRESUMO
Lactoferrin, lysozyme, interferon, and neopterin levels were determined in parotid saliva from 44 individuals with different clinical stages of human immunodeficiency virus (HIV) infection and 19 HIV-seronegative controls. The secretory output of individual components was calculated according to the fluid flow rate. No parotid interferon activity was found in any of the HIV-infected subjects or controls, and no significant differences in parotid lysozyme or neopterin outputs were observed. The lactoferrin output was significantly decreased in HIV-seropositive subjects in parallel with their markedly reduced parotid secretory IgA output. This combined deficiency of parotid lactoferrin and secretory IgA may well contribute to the frequent oral infections seen in subjects with HIV infection.
Assuntos
Infecções por HIV/imunologia , Doenças da Boca/imunologia , Glândula Parótida/imunologia , Saliva/imunologia , Adulto , Biopterinas/análogos & derivados , Biopterinas/análise , Infecções por HIV/complicações , Humanos , Interferons/análise , Lactoferrina/análise , Masculino , Doenças da Boca/complicações , Muramidase/análise , NeopterinaRESUMO
BACKGROUND: The possibility that human cytomegalovirus (HCMV) may infect porcine endothelial cells (ECs) was investigated. This may be relevant during xenotransplantation of porcine cells or organs into human recipients. METHODS: HCMV was inoculated into low-passage porcine ECs. Replication of virus was detected by development of characteristic cytopathogenic effect. Appearance of immediate early, early, and late antigens was studied by immunocytochemical staining. Infectious virus was detected in human fibroblast cells. Presence of HCMV RNA was studied by Northern Blot and reverse transcriptase polymerase chain reaction. RESULTS: All parameters indicated that a fresh clinical HCMV isolate productively infects porcine ECs. The same cells do not fully support replication of the laboratory strain Ad 169. CONCLUSION: Our results may indicate the possibility of cross-species infectivity of HCMV to porcine cells.
Assuntos
Infecções por Citomegalovirus/transmissão , Citomegalovirus/fisiologia , Endotélio Vascular/virologia , Suínos , Zoonoses , Animais , Células Cultivadas , Citomegalovirus/genética , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/patologia , Endotélio Vascular/citologia , Humanos , RNA Viral/análiseRESUMO
BACKGROUND: Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. Because no CMV-prophylaxis is given and ganciclovir is used only as deferred therapy for CMV disease at our center, we have been able to study the natural course of CMV infections. The aim was to assess risk factors for CMV infection and disease and thus identify subgroups of patients likely to benefit from CMV prophylaxis or preemptive therapy. METHODS: Between October 1994 and July 1997, 477 consecutive renal transplant recipients (397 first transplants and 80 retransplants) were included in the study. The patients were followed prospectively for 3 months with serial measurements of CMV pp65 antigen for monitoring activity of CMV infections. RESULTS: The incidence of CMV infections in first transplants was 68% in D+R- and D+/-R+ serostatus groups, whereas the incidence of CMV disease was higher in D+R- (56%) than in D+/-R+ (20%, P<0.001). No difference in severity of CMV disease in D+R- and D+/-R+ was seen except for an increased incidence of hepatitis in primary infections. One of 14 deaths could be associated with CMV disease in a seropositive recipient. Cox regression analysis showed that rejection (RR 2.5, P<0.01) and serostatus group D+R- (RR 3.9, P<0.001) were significant risk factors for development of CMV disease. The maximum CMV pp65 antigen count had significant correlation to disease only in CMV seropositive recipients, P<0.001. Conclusion. Renal transplant recipients can safely be given deferred ganciclovir therapy for CMV disease if they are intensively monitored for CMV infection. Patients with primary CMV infection (D+R-), CMV infected patients undergoing anti-rejection therapy and R+ patients with high CMV pp65 counts seem to have a particular potential for benefit from preemptive anti-CMV-therapy.
Assuntos
Citomegalovirus/imunologia , Transplante de Rim , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/prevenção & controle , Feminino , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
Co-infections or co-habitations of cells by two or more viruses may occur in the human organism. Human cytomegalovirus (HCMV) and the human polyomavirus BK (BKV) have common host cells and may both establish lifelong latency/persistence following primary infection. Both viruses may become reactivated by immunosuppression or other conditions which upset host-virus balance, and they encode gene products with the inherent potential of acting as heterologous transacting factors for expression of cellular or viral genes. It has been shown that HCMV induces gene expression and replication of primate polyomaviruses. We now demonstrate that BKV is able to enhance the expression of HCMV immediate early (IE1 and 2) as well as the early (E) protein pp65 during double infections in semi-permissive cells. By transfection experiments it was established that the phenomenon is due to heterologous transcriptional transactivation of the HCMV major IE promoter (MIEP) by the BKV large T antigen, without contribution from the small t antigen.
Assuntos
Antígenos Virais de Tumores/fisiologia , Vírus BK/imunologia , Citomegalovirus/genética , Regulação Viral da Expressão Gênica , Células Cultivadas , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , Elementos Facilitadores Genéticos , Genes Precoces , Humanos , Regiões Promotoras Genéticas , Ativação Transcricional , Transfecção , Células Tumorais CultivadasRESUMO
HIV multiplication in blood-derived macrophages was slightly inhibited by pretreatment of cells with interferon-gamma or by preincubation of virus with serum containing antibodies against HIV. When these pretreatments were combined, the HIV titres observed a short time after infection were enhanced. This effect was blocked by antibodies against Fc receptors but not by antibodies against CD4 receptors. Interferon enhanced the expression of Fc receptors on macrophages. The results indicate that IFN-gamma, in appropriate combinations with HIV-antibody-containing human serum, may enhance the rate of HIV infection of macrophages.
Assuntos
Infecções por HIV/sangue , HIV/isolamento & purificação , Interferon gama/farmacologia , Macrófagos/microbiologia , Anticorpos , Ligação Competitiva , Antígenos CD4/imunologia , Ensaio de Imunoadsorção Enzimática , HIV/imunologia , Anticorpos Anti-HIV/imunologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/ultraestrutura , Receptores Fc/fisiologiaRESUMO
The ability to mount an oxidative burst (OB) in response to medium, zymosan and phorbol myristate acetate (PMA) was assessed in human blood monocytes cultured for 1 day (MO) and monocyte-derived macrophages cultured for 10 days (MDM). Further, the effect of recombinant interferons (IFNs) on OB generation was examined. The OB was measured as a reduction of nitroblue tetrazolium (NBT). Unstimulated and stimulated NBT reduction per cell nucleus and the ratio of stimulated/unstimulated NBT reduction was not significantly different in cells cultured for 1 and 10 days. In MO, IFN-gamma stimulated the OB when co-stimulated with zymosan or PMA. IFN-alpha reduced MO adherence. When the lower adherence was corrected for, IFN-alpha enhanced NBT reduction. In MDM, a high concentration of IFN-gamma stimulated the OB without co-stimulation, in lower concentrations the presence of a co-stimulant was necessary for OB stimulation. IFN-alpha/beta enhanced the OB in response to PMA, suggesting that IFN-alpha/beta has a role in macrophage activation.
Assuntos
Interferons/farmacologia , Macrófagos/metabolismo , Monócitos/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Zimosan/farmacologia , Adesão Celular/efeitos dos fármacos , Humanos , Técnicas In Vitro , Ativação de Macrófagos/efeitos dos fármacos , Nitroazul de Tetrazólio/metabolismo , OxirreduçãoRESUMO
To detect possible interactions between lipid-based total parenteral nutrition (TPN) substrates and mononuclear phagocytes, ultrastructural in vitro and in vivo studies were carried out on material from pigs. Mononuclear phagocytes isolated from peripheral blood, phagocytosed lipid after incubation with 1 mg/ml Intralipid for 24 h. Similarly, lipid was taken up by intravascular macrophages in the lungs and liver after central venous administration of TPN containing 2.3 g/kg body weight/day of Intralipid for 5-7 weeks. Lipid accumulation was almost exclusively found intravascularly in the lungs and liver, and not in macrophages obtained from bronchoalveolar lavage fluid. A morphometric study of the lung capillaries showed that the macrophages in TPN animals had increased in size and number, and occupied a larger portion of the capillary lumina. The macrophages appeared to be activated, but the endothelial lining was well preserved. Free intravascular lipid droplets had a diameter both in vitro and in vivo of about 0.5 micron, indicating good stability of the emulsion. We suggest that the lipid uptake stimulates the macrophages and thereby plays a role in the lung tissue inflammation seen in response to long-term lipid-based TPN in pigs.
Assuntos
Metabolismo dos Lipídeos , Pulmão/irrigação sanguínea , Pulmão/patologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/patologia , Nutrição Parenteral , Animais , Lipídeos/administração & dosagem , Fígado/imunologia , Fígado/patologia , Fígado/ultraestrutura , Pulmão/ultraestrutura , Macrófagos Alveolares/ultraestrutura , Fagocitose , Suínos , Fatores de TempoRESUMO
The effect of human cytomegalovirus (HCMV) infection on adhesiveness and invasiveness of Salmonella typhimurium was examined in cells permissive (human embryo fibroblasts (HE)), semipermissive (A549) and nonpermissive (HEp-2) for the virus. Preinfection of the cells with HCMV induced enhanced adhesiveness and invasiveness of bacteria in the permissive HE cells. In the semipermissive A549 cells, where HCMV immediate-early (IE) mRNA transcripts and IE proteins were detected, a significant effect on the initial phase of invasiveness, the adherence phase, was demonstrated. HCMV had no effect on invasiveness of S. typhimurium in nonpermissive HEp-2 cells. Neither HCMV IE transcripts nor IE proteins could be detected in these cells.