MARIA CRISTINA DOMINGUES DA SILVA FINK
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
10 resultados
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- Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen(2013) OLIVAL, Guilherme S. do; FARIA, Thiago S.; NALI, Luiz H. S.; OLIVEIRA, Augusto C. P. de; CASSEB, Jorge; VIDAL, Jose E.; CAVENAGHI, Vitor B.; TILBERY, Charles P.; MORAES, Lenira; FINK, Maria C. S.; SUMITA, Laura M.; PERRON, Herve; ROMANO, Camila M.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.
- Variable sources of Bk virus in renal allograft recipients(2019) URBANO, Paulo Roberto P.; NALI, Luiz H. da Silva; OLIVEIRA, Renato dos R.; SUMITA, Laura M.; FINK, Maria Cristina D. da Silva; PIERROTTI, Ligia C.; BICALHO, Camila da Silva; DAVID-NETO, Elias; PANNUTI, Claudio S.; ROMANO, Camila M.BK virus is the causative agent of polyomavirus-associated nephropathy, a major cause of kidney transplant failure affecting 1%-10% of recipients. Previous studies that investigated the viral source on the kidney recipient pointed that the donor is implicated in the origin of human polyomavirus BK (BKPyV) infection in recipients, but giving the low genetic variability of BKPyV this subject is still controversial. The aim of this study was to determine if BKPyV replicating in kidney recipients after transplantation is always originated from the donor. Urine and blood samples from 68 pairs of living donors and kidney recipients who underwent renal transplantation from August 2010-September 2011 were screened for BKPyV by real time polymerase chain reaction. Only three recipients presented viremia. When both donors and recipients were BKPyV positive, a larger fragment of VP1 region was obtained and sequenced to determine the level of similarity between them. A phylogenetic tree was built for the 12 pairs of sequences obtained from urine and high level of similarity among all sequences was observed, indicating that homology inferences for donor and recipient viruses must be cautiously interpreted. However, a close inspection on the donor-recipient pairs sequences revealed that 3 of 12 pairs presented considerably different viruses and 4 of 12 presented mixed infection, indicating that the source of BKPyV infection is not exclusively derived from the donor. We report that about 60% of the renal recipients shed BKPyV genetically distinct from the donor, confronting the accepted concept that the donor is the main source of recipients' infection.
- Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients(2014) NALI, Luiz Henrique da Silva; MORAES, Lenira; FINK, Maria Cristina Domingues; CALLEGARO, Dagoberto; ROMANO, Camila Malta; OLIVEIRA, Augusto Cesar Penalva deNatalizumab 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.
- Polyomavirus Detection in Multiple Sclerosis Patients Under Natalizumab Therapy: Profile and Frequency of Urinary Shedding(2017) NALI, Luiz Henrique; FINK, Maria Cristina; OLIVAL, Guilherme S. do; MORAES, Lenira; CALLEGARO, Dagoberto; TILBERY, Charles Peter; VIDAL, Jose Ernesto; SUMITA, Laura Masami; OLIVEIRA, Augusto C. Penalva de; ROMANO, Camila M.Patients undergoing Natalizumab (NTZ) therapy are at risk of progressive multifocal leukoence-phalopathy (PML). Besides John Cunningham virus (JCV), BK polyomavirus might represent an additional concern for such patients since it can also infect CNS cells. Currently, data regarding the presence of anti-JCV antibodies added to previous immunosuppressive therapy and prolonged NTZ therapy has been used to classify patients at risk of developing PML. Here, we investigated the profile shedding of JCV and BKV in multiple sclerosis (MS) patients during treatment with NTZ. Serial blood and urine samples from 97 MS patients receiving either NTZ or beta-interferon were investigated for polyomavirus shedding. While all blood samples tested negative, 36% of the patients shed polyomavirus in the urine in at least one time point. From these, 21.7%, 9.3%, and 5.1% shed JCV, BKV, and both polyomavirus, respectively. No difference was observed between the rates of urinary shedding of patients treated with NTZ (38.9%) and patients treated with other drugs (34.5%), also no PML event was diagnosed during the follow-up. Therefore, urinary shedding might not be interfered by therapy condition. In our study, we also observed 14/ 27 (52%) of anti-JCV antibodies prevalence, and nearly half of them (42%) did not present any event of urinary shedding during the follow-up. (C) 2016 Wiley Periodicals, Inc.
conferenceObject Continuos excretion of JC virus and BK virus in one multiple sclerosis patient undergoing natalizumab treatment: one year follow up(2012) NALI, L. H. S.; SUMITA, L. M.; FINK, M. C. D.; OLIVAL, G. S.; SANTIAGO, T. F.; V, J. E. Bermudez; MORAES, L.; CAVENAGHI, V; TILBERY, C. P.; CALLEGARO, D.; CASSEB, J. S.; PENALVA-DE-OLIVEIRA, A. C.; ROMANO, C. M.conferenceObject Research of locus Xq22.3 as transcription source for endogenous retrovirus and its association with the multiple sclerosis etiology(2012) OLIVAL, G. S.; THOMAZ, R. B.; TILBERY, C.; FARIA, T. S.; NALI, L. S.; OLIVEIRA, A. C. Penalva de; CASSEB, J. S.; BERMUDEZ, J. V.; CAVENAGHI, V.; MORAES, L.; FINK, C.; SUMITA, L.; ROMANO, C. M.- Occurrence, genotypic characterization, and patterns of shedding of human polyomavirus JCPyV and BKPyV in urine samples of healthy individuals in SAo Paulo, Brazil(2016) URBANO, Paulo Roberto Palma; OLIVEIRA, Renato Reis; ROMANO, Camila Malta; PANNUTI, Claudio Sergio; FINK, Maria Cristina Domingues da SilvaThe 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. J. Med. Virol. 88:153-158, 2016. (c) 2015 Wiley Periodicals, Inc.
- Pre-transplant shedding of BK virus in urine is unrelated to post-transplant viruria and viremia in kidney transplant recipients(2016) BICALHO, C. S.; OLIVEIRA, R. R.; PIERROTTI, L. C.; FINK, M. C. D. S.; URBANO, P. R. P.; NALI, L. H. S.; LUNA, E. J. A.; ROMANO, C. M.; DAVID, D. R.; DAVID-NETO, E.; PANNUTI, C. S.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.
conferenceObject Human herpesvirus in multiple sclerosis patients(2012) THOMAZ, R. B.; OLIVAL, G. S.; TILBERY, C. P.; BERMUDEZ, J. V.; NALI, L. H. S.; ROMANO, C. M.; MORAES, L.; CALLEGARO, D.; CAVENAGHI, V.; CASSEB, J. S.; OLIVEIRA, A. C. Penalva de; FINK, C.; SUMITA, L. S.- Multiple sclerosis and herpesvirus interaction(2013) OLIVAL, Guilherme Sciascia do; LIMA, Bruna Mendonca; SUMITA, Laura M.; SERAFIM, Vitor; FINK, Maria Cristina; NALI, Luis Henrique; ROMANO, Camila Malta; THOMAZ, Rodrigo Barbosa; CAVENAGHI, Vitor Breseghello; TILBERY, Charles Peter; PENALVA-DE-OLIVEIRA, Augusto CesarMultiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.