CAMILA MALTA ROMANO
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
13 resultados
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- Viremia and viruria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient(2019) PIERROTTI, Ligia Camera; URBANO, Paulo Roberto Palma; NALI, Luiz Henrique da Silva; ROMANO, Camila Malta; BICALHO, Camila da Silva; ARNONE, Marcelo; VALENTE, Neusa Sakai; PANNUTI, Claudio Sergio; DAVID-NETO, Elias; AZEVEDO, Luiz SergioTrichodysplasia 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 Immunosuppression was changed: mycophenolate was withdrawn, tacrolimus reduced and everolimus added.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.
- 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.
- Expression of human endogenous retrovirus K and W in babies(2017) NALI, L. H. S.; OLIVEIRA, A. C. S.; ALVES, D. O.; CALEIRO, G. S.; NUNES, C. F.; GERHARDT, D.; SUCCI, R. C. M.; ROMANO, Camila M.; MACHADO, D. M.Here we determined the relative expression of HERV-K and W proviruses in HIV infected and non-infected mothers as well as their respective babies up to 1 year-old. HIV-infected mothers, their babies and uninfected control groups presented expression of both HERV-K and HERV-W with relatively high frequency. While the level of HERV-K expression was similar among groups, the level of HERV-W expression in HIV-infected mothers was four-fold higher than the uninfected mothers from the control group (p < 0.01). HERV-W was down regulated in HIV-exposed babies in comparison to non-exposed babies. To our knowledge, this is the first report of HERV transcriptional activity in babies from 0-1 year-old.
- 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.
- New findings about trichodysplasia spinulosa-associated polyomavirus (TSPyV)-novel qPCR detects TSPyV-DNA in blood samples(2016) URBANO, Paulo R.; NALI, Luiz H. S.; BICALHO, Camila S.; PIERROTTI, Ligia C.; DAVID-NETO, Elias; PANNUTI, Claudio S.; ROMANO, Camila M.A new real-time PCR assay for trichodysplasia spinulosa associated polyomavirus (TSPyV) DNA detection was designed, and blood samples from kidney transplant recipients and healthy individuals were screened. TSPyV-DNA was not detected in blood from healthy individuals, but 26.8% of kidney recipients presented TSPyV-DNA. This is the first report of TSPyV viremia.
- 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 Profile of HERV-W expression in multiple sclerosis patients(2016) NALI, L. H.; SILVA, I. T. da; OLIVAL, G. S. do; DIAS-NETO, E.; SILVA, D. F.; URBANO, P. R.; TILBERY, C. P.; PENALVA-DE-OLIVEIRA, A. C.; ROMANO, C. M.- Whole transcriptome analysis of multiple Sclerosis patients reveals active inflammatory profile in relapsing patients and downregulation of neurological repair pathways in secondary progressive cases(2020) NALI, Luiz H.; OLIVAL, Guilherme S.; SOUSA, Francielle T. G.; OLIVEIRA, Ana Carolina S. de; MONTENEGRO, Horacio; SILVA, Israel T. da; DIAS-NETO, Emamnuel; NAYA, Hugo; SPANGENBERG, Lucia; PENALVA-DE-OLIVEIRA, Augusto C.; ROMANO, Camila M.Background: Multiple sclerosis (MS) is an inflammatory autoimmune neurologic disease that causes progressive destruction of myelin sheath and axons. Affecting more than 2 million people worldwide, MS may presents distinct clinical courses. However, information regarding key gene expression and genic pathways related to each clinical form is still limited. Objective: To assess the whole transcriptome of blood leukocytes from patients with remittent-recurrent (RRMS) and secondary-progressive (SPMS) forms to explore the gene expression profile of each form. Methods: Total RNA was obtained and sequenced in Illumina HiSeq platform. Reads were aligned to human genome (GRCh38/hg38), BAM files were mapped and differential expression was obtained with DeSeq2. Up or downregulated pathways were obtained through Ingenuity IPA. Pro-inflammatory cytokines levels were also assessed. Results: The transcriptome was generated for nine patients (6 SPMS and 3 RRMS) and 5 healthy controls. A total of 731 and 435 differentially expressed genes were identified in SPMS and RRMS, respectively. RERE, IRS2, SIPA1L1, TANC2 and PLAGL1 were upregulated in both forms, whereas PAD2 and PAD4 were upregulated in RRMS and downregulated in SPMS. Inflammatory and neuronal repair pathways were upregulated in RRMS, which was also observed in cytokine analysis. Conversely, SPMS patients presented IL-8, IL-1, Neurothrophin and Neuregulin pathways down regulated. Conclusions: Overall, the transcriptome of RRMS and SPMS clearly indicated distinct inflammatory profiles, where RRMS presented marked pro-inflammatory profile but SPMS did not. SPMS individuals also presented a decrease on expression of neuronal repair pathways.
- 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.