LUIZ HENRIQUE DA SILVA NALI
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- 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.
- 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 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.