SUMMARYObjective: To evaluate the prevalence of the urinary excretion of BKV and JCV in HIV-infected patients without neurological symptoms. Methods: Urine samples from HIV-infected patients without neurological symptoms were tested for JC virus and BK virus by PCR. Samples were screened for the presence of polyomavirus with sets of primers complementary to the early region of JCV and BKV genome (AgT). The presence of JC virus or BK virus were confirmed by two other PCR assays using sets of primers complementary to the VP1 gene of each virus. Analysis of the data was performed by the Kruskal-Wallis test for numerical data and Pearson or Yates for categorical variables. Results: A total of 75 patients were included in the study. The overall prevalence of polyomavirus DNA urinary shedding was 67/75 (89.3%). Only BKV DNA was detected in 14/75 (18.7%) urine samples, and only JCV DNA was detected in 11/75 (14.7%) samples. Both BKV and JCV DNA were present in 42/75 (56.0%) samples. Conclusion: In this study we found high rates of excretion of JCV, BKV, and simultaneous excretion in HIV+ patients. Also these results differ from the others available on the literature.
Human endogenous retroviruses (HERVs) arise from ancient infections of the host germline cells by exogenous retroviruses, constituting 8% of the human genome. Elevated level of envelope transcripts from HERVs-W has been detected in CSF, plasma and brain tissues from patients with Multiple Sclerosis (MS), most of them from Xq22.3, 15q21.3, and 6q21 chromosomes. However, since the locus Xq22.3 (ERVWE2) lack the 5′ LTR promoter and the putative protein should be truncated due to a stop codon, we investigated the ERVWE2 genomic loci from 84 individuals, including MS patients with active HERV-W expression detected in PBMC. In addition, an automated search for promoter sequences in 20 kb nearby region of ERVWE2 reference sequence was performed. Several putative binding sites for cellular cofactors and enhancers were found, suggesting that transcription may occur via alternative promoters. However, ERVWE2 DNA sequencing of MS and healthy individuals revealed that all of them harbor a stop codon at site 39, undermining the expression of a full-length protein. Finally, since plaque formation in central nervous system (CNS) of MS patients is attributed to immunological mechanisms triggered by autoimmune attack against myelin, we also investigated the level of similarity between envelope protein and myelin oligodendrocyte glycoprotein (MOG). Comparison of the MOG to the envelope identified five retroviral regions similar to the Ig-like domain of MOG. Interestingly, one of them includes T and B cell epitopes, capable to induce T effector functions and circulating Abs in rats. In sum, although no DNA substitutions that would link ERVWE2 to the MS pathogeny was found, the similarity between the envelope protein to MOG extends the idea that ERVEW2 may be involved on the immunopathogenesis of MS, maybe facilitating the MOG recognizing by the immune system. Although awaiting experimental evidences, the data presented here may expand the scope of the endogenous retroviruses involvement on MS pathogenesis.
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
Trichodysplasia spinulosa (TS) is a rare disease associated with immunosuppression and induced by a polyomavirus denominated Tricodisplasia Polyomavirus (TSPyV). We report a case of TS 6 months after kidney transplantation in a 65 years-old woman under immunosuppression therapy with prednisone, mycophenolate and tacrolimus. The patient developed follicular papules on the face with a thickening of the skin and alopecia of the eyebrows, leading to distortion of the face and a leonine appearance characteristic of the disease. The skin biopsy confirmed the clinical diagnosis and the presence of TSPyV DNA in the skin was detected. Staining for SV40 was positive. Immunosuppression was changed: mycophenolate was withdrawn, tacrolimus reduced and everolimus added. Intravenous cidofovir and later on leflunomide were added. Although the literature has reported clinical success with topical cidofovir, we were unable to use it because this drug is not available. There was an improvement of skin lesions and on cosmetic appearance. The patient had three rejections (one clinically diagnosed and two other biopsy proven), progressed with renal failure and graft loss. Retrospective analysis of stored urine and blood samples detected TSPyV DNA in some of those samples two months before the TS clinical development. This case highlights the TSPyV detection in blood and urine samples before the development of skin lesions. K E Y W O R D S kidney transplant, polyomavirus, trichodysplasia spinulosa, viremia, viruria
Background Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases. Methods Here the expression of Endogenous retroviruses K and W (HERV-K and HERV-W) was determined in blood from moderately and severely affected ME/CFS patients through real time PCR. Results HERV-K was overexpressed only in moderately affected individuals but HERV-W showed no difference. Conclusions This is the first report about HERV-K differential expression in moderate ME/CFS. Although the relationship between HERVs and ME/CFS has yet to be proven, the observation of this phenomenon deserves further attention.
BK virus-(BKV) associated nephropathy (BKVN) is a major cause of allograft injury in kidney transplant recipients. In such patients, subclinical reactivation of latent BKV infection can occur in the pre-transplant period. The purpose of this study was to determine whether urinary BKV shedding in the immediate pre-transplant period is associated with a higher incidence of viruria and viremia during the first year after kidney transplantation. We examined urine samples from 34 kidney transplant recipients, using real-time quantitative polymerase chain reaction to detect BKV. Urine samples were obtained in the immediate pre-transplant period and during the first year after transplant on a monthly basis. If BKV viruria was detected, blood samples were collected and screened for BKV viremia. In the immediate pre-transplant period, we detected BKV viruria in 11 (32.3%) of the 34 recipients. During the first year after transplantation, we detected BKV viruria in all 34 patients and viremia in eight (23.5%). We found no correlation between pre-transplant viruria and post-transplant viruria or viremia (p = 0.2). Although reactivation of latent BKV infection in the pre-transplant period is fairly common among kidney transplant recipients, it is not a risk factor for post-transplant BKV viruria or viremia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.