RESUMO
OBJECTIVE: To assess the predictive value of JC virus (JCV) PCR in cerebrospinal fluid (CSF) in the diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: We conducted a retrospective database query to identify patients with positive CSF JCV PCR. Clinical features, final diagnosis and quantitative PCR results were obtained. RESULTS: A positive CSF JCV PCR had a PPV of 10.4% for the diagnosis of PML. A weakly positive PCR had a PPV of 1.6%, whereas a moderately to highly positive PCR had a PPV of 92.3%. A PPV of 0.0% was observed in immunocompetent patients and in patients without compatible clinical or radiological features. CONCLUSIONS: A false-positive CSF JCV PCR is highly prevalent in our clinical practice. This test should be reserved for patients with a clinical suspicion of PML and the quantitative result of the PCR should be taken into account when making the diagnosis of PML.
Assuntos
Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Reação em Cadeia da Polimerase , Carga Viral/métodos , DNA Viral/sangue , DNA Viral/líquido cefalorraquidiano , DNA Viral/urina , Reações Falso-Positivas , Humanos , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/sangue , Leucoencefalopatia Multifocal Progressiva/urina , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/diagnóstico , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
Progressive multifocal leukoencephalopathy (PML) and PML immune reconstitution inflammatory syndrome (PML-IRIS) can be devastating neurological processes associated with HIV, but limited knowledge of their characteristics in the established antiretroviral therapy (ART) era is available. We conducted a case series to evaluate the clinical course of PML and PML-IRIS at our urban safety-net hospital in Atlanta, GA. All HIV-positive individuals with a positive John Cunningham virus DNA polymerase chain reaction in the spinal fluid between May 1, 2013 to June 1, 2017 were identified from the electronic health records (EHRs) using the HIV Disease Registry. Demographics, symptom presentation, laboratory data, imaging results, treatment, and outcomes were abstracted from the EHR. PML and PML-IRIS were defined using the American Association of Neurology criteria. Of the 32 individuals identified, 6 (19%) were felt to have asymptomatic positive results. Of the remainder, 15 (58%) HIV-positive patients had PML and 11 (42%) PML-IRIS (2 with an unmasking presentation and 9 with a paradoxical presentation). The most common presenting symptoms were motor weakness (18, 69%), cognitive deficits (15, 58%), and dysarthria (11, 42%). Corticosteroids were used in 12 patients and maraviroc in 3 patients. Outcomes were dismal with 7 (47%) patients with PML and 9 (82%) with PML-IRIS dying or being referred to hospice, with median survival times of 266 days in the PML group and 109 days in the PML-IRIS group. Despite widespread access to ART, patients with PML continue to have poor outcomes, particularly among those who develop PML-IRIS. More research is needed to understand the risks for and prevention of PML-IRIS.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Sistema de Registros , Adulto , Infecções Assintomáticas/epidemiologia , Feminino , Georgia/epidemiologia , Humanos , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/epidemiologia , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/epidemiologiaRESUMO
To date, only one case of BK polyomavirus (BKPyV) encephalitis combined with transplant-associated thrombotic microangiopathy has been reported in an hematopoietic stem cell transplantation (HCT) recipient. We report the case of an HCT recipient who developed thrombotic microangiopathy and subsequent BKPyV encephalitis. She died despite treatment with cidofovir, ciprofloxacin, and intravenous immunoglobulin without improvement in mental status. Early suspicion of BKPyV encephalitis in an HCT recipient presenting with altered mental status and hemorrhagic cystitis is important.
Assuntos
Vírus BK/isolamento & purificação , Cistite/tratamento farmacológico , Encefalite/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Polyomavirus/tratamento farmacológico , Microangiopatias Trombóticas/complicações , Infecções Tumorais por Vírus/tratamento farmacológico , Anemia Hemolítica/etiologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Vírus BK/fisiologia , Cidofovir , Ciprofloxacina/administração & dosagem , Ciprofloxacina/uso terapêutico , Cistite/complicações , Cistite/virologia , Citosina/administração & dosagem , Citosina/análogos & derivados , Citosina/uso terapêutico , Encefalite/líquido cefalorraquidiano , Encefalite/diagnóstico por imagem , Encefalite/virologia , Evolução Fatal , Feminino , Hematúria/etiologia , Humanos , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Organofosfonatos/administração & dosagem , Organofosfonatos/uso terapêutico , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/diagnóstico por imagem , Infecções por Polyomavirus/virologia , Microangiopatias Trombóticas/etiologia , Tomografia Computadorizada por Raios X , Transplante Homólogo/efeitos adversos , Infecções Tumorais por Vírus/líquido cefalorraquidiano , Infecções Tumorais por Vírus/diagnóstico por imagem , Infecções Tumorais por Vírus/virologia , Ativação Viral/imunologiaAssuntos
Infecções por HIV/complicações , Vírus JC , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Infecções por Polyomavirus/tratamento farmacológico , Antimaláricos/uso terapêutico , Encéfalo/patologia , Contagem de Linfócito CD4 , Evolução Fatal , HIV-1 , Humanos , Leucoencefalopatia Multifocal Progressiva/etiologia , Masculino , Mefloquina/uso terapêutico , Pessoa de Meia-Idade , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/complicações , Prognóstico , Carga ViralRESUMO
BACKGROUND: Progressive multifocal leukoencephalopathy (PML), a rare but fatal demyelinating disease caused by JC virus (JCV), occurs mainly in immunocompromised patients. As PML develops in individuals with various underlying disorders sporadically and infrequently, a nationwide survey of PML is difficult. This study was conducted to elucidate the characteristics of PML in Japan through an internet-assisted laboratory surveillance program. METHODS: A diagnostic support system for PML was established using a real-time PCR assay of JCV DNA in cerebrospinal fluid (CSF), and requests for testing were received from clinicians via specialized websites. Medical histories of patients were collected through standardized questionnaires, and a database of CSF JCV loads and clinical information was created and analyzed. RESULTS: For 4 years from April 2007 to March 2011, CSF specimens from 419 patients were tested. Forty-eight individuals were found positive for JCV DNA in their CSF and were diagnosed with PML. PML primarily occurred not only in HIV-positive patients (33.3%) but also in patients with hematologic disorders after receiving stem cell transplantation, chemotherapy, and/or immunosuppressive treatment (39.6%). The frequencies of PML cases among the subjects in these two categories were 20.3% and 23.5%, respectively. Although no significant features were observed with respect to CSF JCV loads in PML patients with an HIV infection or hematologic disorder, males were predominant in both groups (100% and 89.5%, respectively). The proportion of PML cases with autoimmune disorders (6.3%) or solid-organ transplants (2.1%) was smaller than those with HIV infection or hematologic disorders, probably due to the limited availability of therapeutic monoclonal antibodies and transplantation from brain dead donors. CONCLUSIONS: The results suggest that the internet-assisted laboratory surveillance program might be a useful strategy for collecting precise real-time information on PML on a national level. The current database provides important background information for the diagnosis and treatment of patients with risk factors for PML.
Assuntos
Técnicas de Laboratório Clínico/estatística & dados numéricos , Internet , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/epidemiologia , Vigilância da População/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Comorbidade , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Registros de Saúde Pessoal , Humanos , Incidência , Lactente , Recém-Nascido , Japão/epidemiologia , Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Leucoencefalopatia Multifocal Progressiva/epidemiologia , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
BK polyomavirus (BKPyV) has recently been postulated as an emerging opportunistic pathogen of the human central nervous system (CNS), but it is not known whether specific strains are associated with the neurotropic character of BKPyV. The presence of BKPyV large T-antigen DNA was examined in 2406 cerebrospinal fluid (CSF) samples from neurological patients with suspected JC polyomavirus infection. Twenty patients had a large T-antigen DNA-positive specimen. The non-coding control region (NCCR) of the BKPyV strains amplified from CSF from these 20 patients, strains circulating in renal and bone marrow transplant recipients and from healthy pregnant women was sequenced. The archetypal conformation was the most prevalent in all groups and 14 of the neurological patients harboured archetypal strains, while the remaining six patients possessed BKPyV with rearranged NCCR similar to previously reported variants from non-neurological patients. Transfection studies in Vero cells revealed that five of six early and four of six late rearranged promoters of these CSF isolates showed significantly higher activity than the corresponding archetypal promoter. From seven of the neurological patients with BKPyV DNA-positive CSF, paired serum samples were available. Five of them were negative for BKPyV DNA, while serum from the remaining two patients harboured BKPyV strains with archetypal NCCR that differed from those present in their CSF. Our results suggest that NCCR rearrangements are not a hallmark for BKPyV neurotropism and the dissemination of a rearranged NCCR from the blood may not be the origin of BKPyV CNS infection.
Assuntos
Vírus BK/genética , Doenças do Sistema Nervoso/virologia , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/virologia , Adolescente , Adulto , Idoso , Pré-Escolar , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Regulação Viral da Expressão Gênica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Doenças do Sistema Nervoso/complicações , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/complicações , Gravidez , Infecções Tumorais por Vírus/líquido cefalorraquidiano , Infecções Tumorais por Vírus/complicações , Adulto JovemRESUMO
While BK virus (BKV) is frequently associated with pathological conditions in bone marrow and renal transplant recipients, BKV infection in neurological individuals has been rarely reported. As a result of a BKV, JCV, and SV40 large T antigen-specific multiplex PCR on 2,062 cerebrospinal fluid (CSF) samples from neurological patients suspicious of JCV infection, we identified 20 subjects with at least 1 CSF specimen positive for BKV large T antigen DNA. Because VP1 protein has been suggested to influence the biological/pathological properties of BKV, we tried to sequence the entire VP1 gene in the BKV-positive neurological patients and succeeded in 14 of the 20 neurological patients. To compare the VP1 sequence of the BKV neurological strains with that of non-neurotropic strains in other clinical situations, full-length VP1 DNA was sequenced in 15 renal and 6 bone marrow transplant recipients positive to BKV-viremia, and in 8 pregnant women as non-pathological controls. An increased (respectively, decreased) tendency for mutations in the BC loop (respectively, EF loop) was observed, and no mutations were detected in the CD, GH, and HI loops. Subtype I was predominant (93%) and compared to archetypal BKV (WW), amino acid substitutions were detected in 4/14 neurological patients, 10/15 renal transplant recipients, 3/6 bone marrow transplant patients, and in all the pregnant women. Each patient group had distinctive VP1 mutations, but these unique substitutions were not present in all patients of this group. However, molecular modeling simulations of the VP1 mutants predicted changes in protein surface properties which might affect the VP1-receptor interaction.
Assuntos
Proteínas do Capsídeo/genética , Doenças do Sistema Nervoso Central/virologia , DNA Viral/análise , Infecções por Polyomavirus/genética , Infecções Tumorais por Vírus/genética , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Vírus BK/genética , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Criança , Pré-Escolar , Análise Mutacional de DNA , DNA Viral/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Multiplex , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/complicações , Gravidez , Infecções Tumorais por Vírus/líquido cefalorraquidiano , Infecções Tumorais por Vírus/complicações , Adulto JovemAssuntos
Síndrome da Imunodeficiência Adquirida/líquido cefalorraquidiano , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Infecções por Polyomavirus/diagnóstico , Polyomavirus/isolamento & purificação , Infecções Tumorais por Vírus/diagnóstico , Síndrome da Imunodeficiência Adquirida/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Polyomavirus/classificação , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/líquido cefalorraquidiano , Infecções Tumorais por Vírus/complicações , Adulto JovemRESUMO
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC polyomavirus. We describe a rare case of PML in a 48-year-old female patient with diffuse large B-cell lymphoma who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy. While she was undergoing five cycles of R-CHOP, she noticed gradually progressive neurological symptoms, such as slurred speech and gait disturbance, and she eventually developed high-grade fever. She also developed Pneumocystis jiroveci pneumonia. The neurological symptoms deteriorated thereafter, and she developed spastic quadriparesis and bulbar palsy. Magnetic resonance imaging showed hyperintensity within the right cerebellar hemisphere on T2-weighted images. Polymerase chain reaction-based tests of the cerebrospinal fluid revealed the presence of the JC virus. Despite intravenous and intrathecal cytarabine treatment, the patient died of PML 5 months after it was diagnosed. Retrospective analysis of her laboratory data showed that her CD4(+) T-cell count before R-CHOP therapy had decreased to 68 microL(-1). Thus, when administering rituximab-containing chemotherapy, even to patients with no prior history of opportunistic infections, attention should be paid to the potential occurrence of PML, particularly in patients with low CD4(+) T-cell counts.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Povo Asiático , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Evolução Fatal , Feminino , Humanos , Japão , Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Leucoencefalopatia Multifocal Progressiva/microbiologia , Leucoencefalopatia Multifocal Progressiva/patologia , Leucoencefalopatia Multifocal Progressiva/virologia , Linfoma Difuso de Grandes Células B/líquido cefalorraquidiano , Linfoma Difuso de Grandes Células B/microbiologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Pessoa de Meia-Idade , Pneumocystis carinii , Pneumonia por Pneumocystis/líquido cefalorraquidiano , Pneumonia por Pneumocystis/induzido quimicamente , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/patologia , Pneumonia por Pneumocystis/virologia , Polyomavirus , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/induzido quimicamente , Infecções por Polyomavirus/microbiologia , Infecções por Polyomavirus/patologia , Infecções por Polyomavirus/virologia , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
OBJECTIVE: To evaluate the possible involvement of JC virus (JCV) in the aetiology of multiple sclerosis (MS), through the comparison of DNA prevalences and viral loads of JCV in cerebrospinal fluid (CSF) of MS patients at the first demyelinating event and subjects suffering from other neurological diseases (OND). METHODS: Seventy-three CSF samples (43 from MS patients at the first demyelinating event, and 30 from patients with OND) were collected; all MS cases were followed up from 1 to 6.7 years after they were diagnosed with clinically definite MS. DNA was extracted and analysed by real-time PCR for the detection of JCV genomes. RESULTS: We found JCV DNA in the CSF of two MS patients (4.7%) with a mean viral load of 2.1 and 6.7 copies/mL of CSF. Among the patients of the OND group we did not find any positive sample. We did not find any difference in the course of the disease between MS patients with and without JCV genomes in their CSF along the follow up. CONCLUSION: JCV seems to be only a bystander in the pathology of MS, and the presence of cell-free viral particles could be related to the immunological activation of the disease, mainly during relapses.
Assuntos
Doenças Desmielinizantes/virologia , Vírus JC/metabolismo , Esclerose Múltipla/virologia , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações , Adulto , DNA Viral/líquido cefalorraquidiano , Doenças Desmielinizantes/líquido cefalorraquidiano , Feminino , Seguimentos , Humanos , Vírus JC/genética , Masculino , Esclerose Múltipla/líquido cefalorraquidiano , Infecções por Polyomavirus/líquido cefalorraquidiano , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções Tumorais por Vírus/líquido cefalorraquidiano , Carga ViralAssuntos
Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/etiologia , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/patologia , Diagnóstico Diferencial , Humanos , Infliximab , Vírus JC/patogenicidade , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/patologia , Imageamento por Ressonância Magnética , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/diagnóstico , Doenças Reumáticas/tratamento farmacológico , Sensibilidade e Especificidade , Infecções Tumorais por Vírus/líquido cefalorraquidiano , Infecções Tumorais por Vírus/diagnósticoRESUMO
JC and BK human polyomaviruses (family Polyomaviridae) may cause severe neurological or urinary tract pathologies in immunocompromised hosts. In the present study, we evaluated a new commercially available PCR and microplate colorimetric hybridization assay for the standardized differential detection of JC virus (JCV) and BK virus (BKV) genomes in clinical samples. This JC/BK Consensus test was first evaluated by testing serial dilutions of JCV or BKV plasmid DNA standards and was then compared with an in-house reference PCR assay for the detection of JC and BK virus genomes in 70 cerebrospinal fluid (CSF) samples of patients with neurological disorders and in 75 serum or plasma samples and 125 urine samples of renal graft recipients. This new test allowed a limit of detection of 10 copies and 1 copy of JC and BK virus genomes, respectively, and was able to differentiate various levels of JCV, BKV, and mixed JCV and BKV DNA genomes in a single reaction tube. Our results showed 100% specificity and sensitivity for the JC/BK Consensus test with CSF samples. With serum or plasma samples, this test had a sensitivity and a specificity of 100% for both JCV and mixed JCV and BKV DNA detection and a sensitivity and a specificity of 100 and 97.8% for BKV DNA detection, respectively. With urine samples, the sensitivity and specificity were 100 and 96.6%, respectively, for JCV DNA detection; 100 and 89.4%, respectively, for BKV DNA detection; and 44.4 and 100%, respectively, for mixed JCV and BKV DNA detection. In conclusion, our data indicate that this new test, the JC/BK Consensus test, is valuable for the sensitive and specific differential detection of single JCV and BKV infections in CSF, serum or plasma, and urine samples. The use of this reliable PCR assay would improve the routine virological diagnosis as well as the clinical care of immunocompromised patients with polyomavirus-related pathologies.
Assuntos
Vírus BK/isolamento & purificação , Vírus JC/isolamento & purificação , Infecções por Polyomavirus , Adulto , Vírus BK/genética , Sangue/virologia , Líquido Cefalorraquidiano/virologia , Humanos , Hibridização Genética , Vírus JC/genética , Reação em Cadeia da Polimerase/métodos , Polyomavirus/isolamento & purificação , Infecções por Polyomavirus/sangue , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/urina , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Urina/virologiaRESUMO
The presence of the human polyomaviruses JCV and BKV in immunocompromised patients can lead to lethal diseases and conditions including progressive multifocal leukoencephalopathy (PML), interstitial nephritis, hemorrhagic cystitis, and kidney allograft rejection. Typically, detection of JCV and BKV in clinical samples has employed standard PCR amplification for viral nucleotide sequences, with subsequent confirmation for viral genome specificity of PCR products by southern blot hybridization. Here, we directly tested a validated PCR-southern protocol with a TaqMan real-time PCR protocol (Applied Biosystems) to assay clinical samples of urine and cerebrospinal fluid. We found equal specificity and sensitivity with both methods. However, real-time allowed for absolute viral-genome quantitation without the use of radionucleotides and was performed more rapidly, in as little as 24 h. Such advantages are important to consider in the effort to establish international standardization of controls for the detection of JCV and BKV, which would aid in screening confidence and the reliable assessment of anti-viral therapies.
Assuntos
Vírus BK/isolamento & purificação , Vírus JC/isolamento & purificação , Infecções por Polyomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Vírus BK/genética , Southwestern Blotting , DNA Viral/análise , Humanos , Vírus JC/genética , Reação em Cadeia da Polimerase/métodos , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/urina , Infecções Tumorais por Vírus/líquido cefalorraquidiano , Infecções Tumorais por Vírus/urinaRESUMO
The regulatory regions of JC virus (JCV) DNAs in the brain of patients with progressive multifocal leukoencephalopathy (PML) (designated as PML-type regulatory regions) are hypervariable, whereas those in the urine and renal tissue of individuals without PML have the same basic structure, designated as the archetype. It is thought that JCV strains with the archetypal regulatory region circulate in the human population. Nevertheless, Monaco et al (J Virol 70: 7004-7012, 1996) reported that PML-type regulatory regions occur in human tonsil tissue. The purpose of this study is to confirm their findings. Using nested polymerase chain reaction (PCR), the authors detected the regulatory region of JCV DNA in the tonsil tissue from 14 (44%) of 32 donors with tonsillitis and tonsilar hypertrophy. Sequencing of the detected regulatory regions indicated that they were identical with the archetypal regulatory regions detected previously or, in a few cases, slightly deviated from the archetype. This finding suggests not only that tonsil tissue is the potential site of initial JCV infection but also that archetypal JCV strains circulate in the human population.
Assuntos
Vírus JC/genética , Vírus JC/isolamento & purificação , Tonsila Palatina/patologia , Tonsila Palatina/virologia , Infecções por Polyomavirus/diagnóstico , Sequências Reguladoras de Ácido Nucleico/genética , Tonsilite/virologia , Adulto , Sequência de Bases , Líquido Cefalorraquidiano/virologia , Feminino , Humanos , Hipertrofia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/líquido cefalorraquidiano , Origem de Replicação/genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Tonsilite/líquido cefalorraquidianoRESUMO
BK virus (BKV) was recovered by polymerase chain reaction (PCR) from brain, kidney, lung, urine, and cerebrospinal fluid (CSF) of a fatal case of BKV tubulointerstitial nephritis with dissemination to lung and brain. Viral regulatory regions in PCR-amplified urine and the lung samples were identical to the archetypal structure, WWT. In the brain and CSF, a rearranged sequence predominated, however. A 94-bp deletion preceded a 71-bp tandem duplication because the same 94-bp segment was deleted from both copies. PCR-amplified regulatory region products were cloned and sequenced to define further the extent of the rearranged structures. Two kidney clones were archetypal, whereas two others were rearranged differently from the brain and from each other. In contrast to the brain clones, the kidney rearrangements seemed to involve deletion after duplication. Three of four brain clones sequenced were identical to the rearrangement found to dominate in the PCR product. A fourth clone showed two short deletions without any duplication. The four CSF clones all showed rearrangements identical to that which was amplified by PCR from CSF and brain. This represents the first molecular analysis of a BKV strain obtained from a central nervous system infection, and it reveals regulatory region rearrangements reminiscent of those described in JC virus from brains with progressive multifocal leukoencephalopathy. We suggest that the presence in the CSF of BKV with a dominant rearranged regulatory region may be useful in the diagnosis of BKV meningoencephalitis secondary to BKV nephritis.