RESUMEN
The risk of developing progressive multifocal leukoencephalopathy (PML), as a consequence of infection/reactivation with JC virus (JCV), is consistent in natalizumab-treated multiple sclerosis (MS) patients, with 430 cases of PML reported so far. The risk of PML is higher in JCV seropositive patients, and it is recommended that only MS patients without JCV antibodies should be enrolled in the treatment postulating that they do not have JCV infection.We have studied forty-two natalizumab-treated MS patients, and urine and blood were collected monthly for up to 60 months. JCV and BK virus (BKV) DNA presence was verified using quantitative real-time PCR assays, and serum anti-JCV antibodies were measured with the Stratify and/or Stratify DxSelect tests.JCV and BKV DNA were not found in the blood samples, whereas they were found at least once in the urine of 21 of 42 (50 %) and of 25/42 (59.5 %) patients, respectively. JCV DNA urinary shedding increased up to month 24 of natalizumab treatment (45.2 %), and the effect of time was significant for JCV (p = 0.04), but not for BKV (p = 0.39). JCV viruria and seropositivity did not completely correlate, since three patients shedding JCV DNA in the urine were seronegative according to the serological tests.The results indicated that natalizumab therapy may increase the rate of JCV urinary shedding. Additionally, we confirmed that the identification of JCV carriers cannot solely rely on serological tests, but sensitive methods for viral DNA detection should be adopted to more precisely identify the truly JCV uninfected cases.
Asunto(s)
Anticuerpos Antivirales/orina , ADN Viral/orina , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/virología , Natalizumab/uso terapéutico , Adulto , Anticuerpos Antivirales/sangre , ADN Viral/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Virus JC/aislamiento & purificación , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/virología , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Seroepidemiológicos , Esparcimiento de Virus/fisiología , Adulto JovenRESUMEN
Prostate cancer (PCA) is the most frequent cancer in men. Exposure to infectious agents has been reported to have a putative role in tumorigenesis. Among the infectious agents, convincing evidence has been accumulated about the human polyomavirus BK (BKV). Tissue fresh specimens, serum, and urine samples were collected from 124 consecutive patients, 56 with PCA and 68 with benign prostatic hyperplasia (BPH). Quantitative PCR assays were used to assess the presence of BKV and JC virus (JCV) genomes. BKV-positive tissue specimens were found in 32.1 and 22.1 % of PCA and BPH patients, respectively; in PCA group the number of positive BKV specimens/patients was significantly higher than in BPH group (3.06 vs. 1.73, p = 0.02). JCV genome was found in the biopsies collected from 28.1 and 24.2 % of PCA and BPH patients, respectively, with no significant difference in the rate of JCV specimens/patients between PCA and BPH groups. Our results support the putative causal association between BKV genome and PCA. Further studies are required to demonstrate the direct pathogenetic role of BKV in the PCA occurrence and progression in order to clear the tempting way of vaccine prophylaxis.
Asunto(s)
Virus BK/aislamiento & purificación , Infecciones por Polyomavirus/complicaciones , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/virología , Infecciones Tumorales por Virus/complicaciones , Anciano , Virus BK/genética , ADN Viral/genética , ADN Viral/aislamiento & purificación , Humanos , Virus JC/genética , Virus JC/aislamiento & purificación , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Suero/virología , Orina/virologíaRESUMEN
The polyomavirus (PyV), JC virus (JCV), is a small nonenveloped DNA virus that asymptomatically infects about 80% of healthy adults and establishes latency in the kidney tissue. In case of immunodeficient hosts, JCV can lytically infect the oligodendrocytes, causing a fatal demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). Although the reactivation of another human PyV, BK virus (BKV), is relatively common and its association with the polyomavirus associated nephropathy (PyVAN) following renal transplantation is proven, JCV replication and its impact on graft function and survival are less well studied. Here we describe the biology of JCV and its pathological features and we review the literature regarding the JCV infection analyzed in the setting of transplantations.
Asunto(s)
Rechazo de Injerto/virología , Virus JC/fisiología , Trasplante de Riñón , Leucoencefalopatía Multifocal Progresiva/virología , Infecciones por Polyomavirus/inmunología , Complicaciones Posoperatorias/virología , Infecciones Tumorales por Virus/inmunología , Animales , Enfermedades Asintomáticas , Rechazo de Injerto/etiología , Humanos , Huésped Inmunocomprometido , Riñón/patología , Riñón/virología , Leucoencefalopatía Multifocal Progresiva/etiología , Infecciones por Polyomavirus/complicaciones , Inmunología del Trasplante , Infecciones Tumorales por Virus/complicaciones , Latencia del VirusRESUMEN
Progressive multifocal leukoencephalopathy (PML) is a severe disease of the central nervous system (CNS), caused by infection with the Polyomavirus JC virus (JCV). Because there are no known treatments or prognostic factors, we performed a long-term study focusing mainly on cerebrospinal fluid (CSF) samples from PML patients to describe the virological features akin to the different forms of the disease. Twenty-eight PML patients were enrolled: 10 HIV-1+ patients with classical PML (CPML), 9 HIV-1+ patients with slowly progressing or stable neurological symptoms (benign PML), 3 HIV-1+ asymptomatic patients, and 6 HIV-1-negative patients. CSF, urine, and blood samples were collected at the enrollment (baseline) and every 6 months afterwards when possible. The JCV DNA and HIV-1 RNA loads were determined, and the JCV strains were characterized. At baseline, the mean CSF JCV load was log 6.0 ± 1.2 copies/ml for CPML patients, log 4.0 ± 1.0 copies/ml for benign PML patients, log 4.2 ± 0.5 copies/ml for asymptomatic PML patients, and log 5.8 ± 1.3 copies/ml for HIV-1-negative PML patients (CPML vs. benign: P < 0.01; CPML vs. asymptomatic: P < 0.05; HIV-1 negative vs. benign: P < 0.01). Organization of the JCV transcriptional control region (TCR) showed unusual archetype structures in two long-term survival patients; the NF1 sequence was found most commonly, whereas the Sp1 binding site was the most common for both CPML patients and HIV-1 negative patients. Our results suggest that the JCV load in the CSF and the organization of the TCR should be considered as indicators of PML clinical outcome.
Asunto(s)
Líquido Cefalorraquídeo/virología , Regulación Viral de la Expresión Génica , Virus JC/fisiología , Leucoencefalopatía Multifocal Progresiva/virología , Adulto , ADN Viral/líquido cefalorraquídeo , ADN Viral/genética , Femenino , Estudios de Seguimiento , Infecciones por VIH/líquido cefalorraquídeo , Infecciones por VIH/virología , Duplicado del Terminal Largo de VIH/genética , VIH-1/genética , Humanos , Virus JC/genética , Leucoencefalopatía Multifocal Progresiva/líquido cefalorraquídeo , Masculino , Neurofibromina 1/genética , ARN Viral/genética , Transcripción Genética , Carga ViralRESUMEN
Rituximab is a chimeric monoclonal antibody reacting with the CD20 antigen on B cells. It has been proposed as treatment for the idiopathic nephrotic syndrome, recurrent idiopathic nephropathy, and focal segmental glomerulosclerosis refractory to steroids. Rituximab influences T-cell immunity and may predispose the patients to opportunistic infections, such as progressive multifocal leukoencephalopathy caused by the polyomavirus JC (JCV). The risk of latent viruses infections/reactivations in pediatric patients receiving monoclonal antibodies is not well known yet. In this longitudinal 6-month study, the effects of rituximab on JCV and BK virus (BKV) replication have been investigated. Blood, serum, and urine samples have been collected monthly from 11 pediatric patients (mean age: 11 years) with the idiopathic nephrotic syndrome and recurrent idiopathic nephropathy, under rituximab therapy. JCV and BKV real-time PCRs and sequencing of the viral protein 1 and the non-coding control region have been conducted. The same investigations have been undertaken on samples collected from eight pediatric patients (controls, mean age: 6 years), with idiopathic nephrotic syndrome or focal segmental glomerulosclerosis, treated with conventional chemotherapy. JCV was detected in the urine of one patient (9%), and one control (12.5%); BKV was found in the urine of 7/11 patients (63.6%) and 2/8 controls (25%) and in blood samples from four patients. No significant difference was found in the mean viral loads and in the viral molecular characterizations between the two groups. The polyomaviruses replication was not associated with rituximab therapy in children.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/farmacología , Virus BK/fisiología , Factores Inmunológicos/farmacología , Virus JC/fisiología , Síndrome Nefrótico/sangre , Replicación Viral , Adolescente , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Virus BK/genética , Niño , Preescolar , ADN Viral/sangre , ADN Viral/orina , Femenino , Genotipo , Humanos , Factores Inmunológicos/uso terapéutico , Virus JC/genética , Trasplante de Riñón/efectos adversos , Estudios Longitudinales , Masculino , Tipificación Molecular , Síndrome Nefrótico/orina , Síndrome Nefrótico/virología , Infecciones por Polyomavirus/sangre , Infecciones por Polyomavirus/orina , Infecciones por Polyomavirus/virología , Secuencias Reguladoras de Ácidos Nucleicos , Rituximab , Análisis de Secuencia de ADN , Infecciones Tumorales por Virus/sangre , Infecciones Tumorales por Virus/orina , Infecciones Tumorales por Virus/virología , Proteínas Virales/genética , Activación ViralRESUMEN
BACKGROUND: Lymphotropic Polyomavirus (LPV) was isolated from a B-lymphoblastoid cell line of an African green monkey. This virus shares some characteristics with human polyomaviruses, but it is antigenically distinct from BK Virus (BKV) and JC Virus (JCV). Seroepidemiological studies revealed that human sera react in the presence of LPV antigens, and, recently, the viral genome was amplified in the peripheral blood from patients affected with HIV-related leukoencephalopathies. OBJECTIVES: The aims of the study were to investigate and compare the presence of LPV DNA with that of JCV and BKV in different biological samples and patient groups. STUDY DESIGN: LPV, JCV and BKV DNA were searched and quantified in peripheral blood and CSF from HIV+ patients and in peripheral blood from healthy subjects. RESULTS: The LPV genome was detected in peripheral blood of both HIV+ patients and healthy subjects, with a prevalence of 7.2% and 4.7% respectively, but not in CSF. However, its presence was less frequent than that of JCV and BKV. CONCLUSIONS: The amplification of LPV genome from human peripheral blood confirms the fact that LPV can infect the human population. LPV DNA was amplified from patients affected with HIV-related leukoencephalopathies but also from HIV patients without neurological disorders and from healthy subjects. Therefore, the results do not support the hypothesis of an association between LPV infection and any neurological disease. However, given their high similarity, it is possible that LPV, as well as BKV and JCV, could establish latency in humans and cause disease only in rare circumstances.
Asunto(s)
Sangre/virología , Líquido Cefalorraquídeo/virología , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/virología , Poliomavirus/aislamiento & purificación , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Cartilla de ADN/genética , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Poliomavirus/clasificación , Prevalencia , Adulto JovenRESUMEN
The major capsid protein, VP1, of the human polyomavirus BK (BKV) is structurally divided into five outer loops, referred to as BC, DE, EF, GH, and HI. The BC loop includes a short region, named the BKV subtyping region, spanning nucleotides 1744-1812 and characterized by non-synonymous nucleotide polymorphisms that have been used to classify different strains of BKV into four subtypes. The aim of this study was to determine if the nucleotide changes clustered within the BKV subtyping region may influence the in vitro growth efficiency of the virus. We therefore infected the African Green Monkey kidney cell line Vero with four different viral strains (named BKV I, II, III, and IV) that contained the nucleotide sequences of the BKV subtypes within the same genomic background. Infected cells were followed for 59 days and viral replication was assessed at different time points by quantitative real-time PCR (Q-PCR). BKV I, II, and IV were successfully propagated over time in Vero cells, whereas BKV III viral loads progressively decreased during the infection course, demonstrating that the non-synonymous nucleotide polymorphisms of subtype III confer a strong disadvantage for viral replication. Since subtype III differs from all the other subtypes at position 68 of the VP1, where Leu is replaced by Gln, we created viral strains bearing Gln at this position together with the polymorphisms of subtypes I, II, IV and tested their growth in Vero cells. Our results demonstrate that this amino acid substitution does not lower the replication efficiency of subtypes I, II, and IV. In conclusion, this study provides further insights to the importance of the BC loop of BKV in the virus life cycle. In addition, given the effect of the amino acid substitutions of the four BKV subtypes on infectious spread of the virus, our results suggest the need to investigate their potential association with BKV related complications.