High prevalence of the simultaneous excretion of polyomaviruses JC and BK in the urine of HIV-infected patients without neurological symptoms in São Paulo, Brazil

Nali, Luiz Henrique da Silva; Centrone, Cristiane de Campos; Urbano, Paulo Roberto Palma; Penalva-de-Oliveira, Augusto César; Vidal, José E.; Miranda, Erique Peixoto; Pannuti, Cláudio Sérgio; Fink, Maria Cristina Domingues da Silva

doi:10.1590/s0036-46652012000400004

Cited by 21 publications

(27 citation statements)

References 42 publications

(47 reference statements)

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“…The combination of immune dysfunction and immunosuppressive therapy could induce JC and BK reactivation; thereby increasing the prevalence of JC and BK viruria in SLE. We did not observe the co-reactivation of JC and BK in patients with SLE although JC and BK co-reactivation was reported in patients with HIV (Nali et al 2012). Lack of evidence of JC and BK co-reactivation in our study suggested that the reactivation of JC and BK in SLE was regulated via different mechanisms and (50) 12 (46) Pyuria (%) 2 (13) 3 (38) 11 (42) Urine protein/creatinine ratio 1.99 ± 3.85 3.95 ± 5.91 1.73 ± 1.81…”

Section: Discussioncontrasting

confidence: 84%

Polyomavirus Reactivation in Pediatric Patients with Systemic Lupus Erythematosus

Rianthavorn

Posuwan

Payungporn

et al. 2012

Tohoku J. Exp. Med.

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Polyomavirus (PyV) infection usually persists without any symptoms in normal individuals. In immunocompromised patients including patients with systemic lupus erythematosus (SLE), PyV reactivation occurs with a high prevalence and can cause severe clinical complications. In this study, reactivation of six PyV [JC, BK, WU, KI, merkel cell (MC) and trichodysplasia spinulosa (TS)] was investigated in terms of prevalence, clinical implications and correlation with urine transforming growth factor (TGF)-β1 expression in 50 SLE patients aged less than 18 years. Clinical characteristics were obtained from medical record review. PyV viruria was assessed by nested polymerase chain reaction. Urine TGF-β1 was measured with ELISA. The mean age was 13 ± 2.8 years. The prevalence of JC and BK viruria was 16% and 32%, respectively. WU, KI, MC and TS were not isolated from any urine specimens. Co-reactivation of 2 PyV was not detected. Urine TGF-β1 levels in patients with JC viruria, with BK viruria and without PyV viruria were 0.27 ± 0.09, 0.10 ± 0.05 and 0.13 ± 0.09 ng/mg of urine creatinine, respectively. Cumulative doses of cyclophosphamide per body weight and urine TGF-β1 levels were higher in JC viruria than in other groups (p < 0.05). The prevalence of JC and BK reactivation was higher in pediatric patients with SLE than in the normal population. JC reactivation in pediatric patients with SLE was correlated with the administration of high-dose cyclophosphamide and increased urine TGF-β1 levels. Surveillance of JC reactivation is recommended in pediatric patients with chronic and severe SLE receiving high-dose cyclophosphamide.

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Section: Discussioncontrasting

confidence: 84%

Polyomavirus Reactivation in Pediatric Patients with Systemic Lupus Erythematosus

Rianthavorn

Posuwan

Payungporn

et al. 2012

Tohoku J. Exp. Med.

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“…An unexpected result, however, was the high rate of co‐infection in this population, 11 of the 71 individuals being found to launch both polyomaviruses. In another study conducted in Brazil, Nali et al [] also reported (56%) much greater rate and simultaneous pouring JCPyV BKPyV, although the study population was composed exclusively of individuals with AIDS.…”

Section: Discussionmentioning

confidence: 95%

Occurrence, genotypic characterization, and patterns of shedding of human polyomavirus JCPyV and BKPyV in urine samples of healthy individuals in São Paulo, Brazil

Urbano

Oliveira

Romano

et al. 2015

Journal of Medical Virology

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The objective of this study was to evaluate the prevalence, genotypic characterization, and determination of the patterns of shedding of human polyomavirus JC (JCPyV) and BK (BKPyV) in consecutive urine samples collected from healthy adults. Urine samples collected monthly over a 6 month period were screened by polymerase chain reaction (PCR) with two sets of primers complementary to the VP1 protein region specific for the JCPyV or BKPyV genome. The viral load of JCPyV and BKPyV in positive samples was determined by quantitative real time PCR. Seventy-one healthy individuals (ages between 18 and 65) were included in the study. Polyomavirus DNA urinary shedding was identified in 44 (62%) of the 71 individuals evaluated: BKPyV only in 16 (22.5%); JCPyV only in 19 (26.7%); and both in 9 (12.7%). Among the 28 individuals shedding JCPyV, the shedding was nearly continuous in 13 (46.4%) and sporadic in 15 (53.6%), whereas all BKPyV shedding was sporadic. A total of 45 (19 BKPyV and 26 JCPyV) strains were identified. Of the BKPyV strains, individuals were observed that excreted all genotypes except genotype 3 and the JCPyV strains, excretion of 5 different genotypes. Evaluating the age of individuals who excrete JCPyV and BKPyV, mostly are young adults, with a slight increase with increasing age and observing the viral load can not draw any parallel between the increase or decrease of age or excreted genotype as there was a wide variation both in the excretion of BKPyV and JCPyV. The high occurrence of isolated or simultaneous urinary shedding of JCPyV and BKPyV in healthy individuals merits further study.

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“…The genetic structure of RR directly affects viral transcription and replication by change the level of DNA/protein and cofactors binding sites, thus leading to distinct cellular tropism 6 . The urinary shedding of JCV with archetype structure is frequent among healthy and immunocompromised individuals 7,8,9,10 , but rearranged forms with deletions, insertions and duplications are usually found in viruses from blood and brain of patients with PML 11,12 . Much less frequently, the rearranged form of JCV can be found in the urine of patients experiencing asymptomatic reactivation 13 .…”

Section: A Short Background Of Pmlmentioning

confidence: 99%

Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients

Nali

Moraes

Fink

et al. 2014

Arq. Neuro-Psiquiatr.

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Natalizumab is currently one of the best options for treatment of patients with Multiple Sclerosis who have failed traditional prior therapies. However, prolonged use, prior immunosuppressive therapy and anti-JCV antibody status have been associated with increased risk of developing progressive multifocal leukoencephalopathy (PML). The evaluation of these conditions has been used to estimate risks of PML in these patients, and distinct (sometimes extreme) approaches are used to avoid the PML onset. At this time, the biggest issue facing the use of Natalizumab is how to get a balance between the risks and the benefits of the treatment. Hence, strategies for monitor JCV-positive patients undergoing Natalizumab treatment are deeply necessary. To illustrate it, we monitored JCV/DNA in blood and urine of a patient receiving Natalizumab for 12 months. We also bring to discussion the effectiveness of the current methods used for risk evaluation, and the real implications of viral reactivation.Keywords: multiple sclerosis, Natalizumab, JCV, risk factors, progressive multifocal leucoencephalopaty, viruria. RESUMO Natalizumabe é atualmente uma das melhores opções para o tratamento de pacientes com Esclerose Múltipla que não respondem aos tratamentos tradicionais. No entanto, o seu uso prolongado, o uso de terapia imunossupressora prévia e o status sorológico antivírus JC têm sido associados com o risco aumentado de desenvolvimento de Leucoencefalopatia Multifocal Progressiva (LEMP). A avaliação destas condições tem sido utilizada para estimar os riscos do desenvolvimento de LEMP nestes pacientes, e abordagens distintas (por vezes extremas) são empregadas para evitar o aparecimento dessa patologia. Atualmente, o grande desafio está em obter um equilíbrio entre os riscos e os benefícios do tratamento com Natalizumabe. Assim, é crucial desenvolver estratégias para monitorar pacientes portadores do vírus JC sob tratamento com Natalizumabe. A título de ilustração, pesquisamos o vírus no sangue e na urina de um paciente sob tratamento durante 12 meses. Também discutimos a eficácia dos métodos atualmente utilizados para avaliação de riscos e as implicações reais de reativação viral.Palavras-chave: esclerose múltipla, Natalizumabe, vírus JC, leucoencefalopatia multifocal progressiva, viruria. Natalizumab (Tysabri), used for treatment of relapsingremitting multiple sclerosis (MS), is a monoclonal antibody directed to the a4b1 integrin, a subunit of an adhesion molecule expressed on the surface of T lymphocytes. The antibodies act by blocking the migration of T Lymphocytes from blood to the CNS through the blood brain barrier (BBB) and attenuate the inflammatory effects 1 . The AFFIRM study showed that monotherapy with Natalizumab (NTZ) for 2 years decreased the relapse rate by 68% and the disability progression rate by 42% compared with placebo 2 . NTZ is well tolerated and the overall incidence of serious adverse events is low. Although the efficacy of NTZ is up to

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High prevalence of the simultaneous excretion of polyomaviruses JC and BK in the urine of HIV-infected patients without neurological symptoms in São Paulo, Brazil

Cited by 21 publications

References 42 publications

Polyomavirus Reactivation in Pediatric Patients with Systemic Lupus Erythematosus

Polyomavirus Reactivation in Pediatric Patients with Systemic Lupus Erythematosus

Occurrence, genotypic characterization, and patterns of shedding of human polyomavirus JCPyV and BKPyV in urine samples of healthy individuals in São Paulo, Brazil

Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients

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