MARIA CRISTINA DOMINGUES DA SILVA FINK

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LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina

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  • article 19 Citação(ões) na Scopus
    HIGH PREVALENCE OF THE SIMULTANEOUS EXCRETION OF POLYOMAVIRUSES JC AND BK IN THE URINE OF HIV-INFECTED PATIENTS WITHOUT NEUROLOGICAL SYMPTOMS IN SAO PAULO, BRAZIL
    (2012) NALI, Luiz Henrique da Silva; CENTRONE, Cristiane de Campos; URBANO, Paulo Roberto Palma; PENALVA-DE-OLIVEIRA, Augusto Cesar; VIDAL, Jose Ernesto; MIRANDA, Erique Peixoto; PANNUTI, Claudio Sergio; FINK, Maria Cristina Domingues da Silva
    Objective: 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.
  • article 26 Citação(ões) na Scopus
    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.
  • article 8 Citação(ões) na Scopus
    Cerebellar degeneration and progressive ataxia associated with HIV-virus infection
    (2018) PEDROSO, Jose Luiz; VALE, Thiago Cardoso; GAMA, Maria Thereza Drumond; RIBAS, Gustavo; KRISTOCHIK, Julio C. G.; GERMINIANI, Francisco M. B.; FINK, Maria Cristina Domingues da Silva; OLIVEIRA, Augusto Cesar Penalva de; TEIVE, Helio A. G.; BARSOTTINI, Orlando G.
    Introduction: The spectrum of neurologic disorders associated with HIV infection is very broad, resulting from direct virus invasion, opportunistic infections, malignancies and toxic effects of drugs. Methods: Among a large cohort of ataxia patients (N = 1050) evaluated between 2008 and 2017, we detected four patients with HIV-infection who developed a pure progressive cerebellar ataxia syndrome combined with cerebellar atrophy. Results: Adverse drug effects, opportunistic infections and malignancies as well as immune reconstitution syndrome were ruled out based on history and laboratory data. The exact pathophysiological mechanisms of ataxia in HIV patients is not very clear, but seems to be immune-mediated or a direct neurotoxic virus effect leading to apoptosis of Purkinje and granular cells. Conclusion: HIV infection should be investigated in adult patients with undetermined sporadic progressive pure ataxia with cerebellar atrophy.
  • article 2 Citação(ões) na Scopus
    BK virus salivary shedding and viremia in renal transplant recipients
    (2019) SARMENTO, Dmitry Jose de Santana; PALMIERI, Michelle; GALVAO, Gustavo Souza; TOZETTO-MENDOZA, Tania Regina; CANTO, Cynthia Motta do; PIERROTTI, Ligia Camera; DAVID-NETO, Elias; AGENA, Fabiana; GALLOTTINI, Marina; PANNUTI, Claudio Sergio; FINK, Maria Cristina Domingues; BRAZ-SILVA, Paulo Henrique
    Objectives: This study aimed to verify the presence of polyomavirus BK (BKPyV) in the saliva of kidney transplant recipients and to correlate it with blood viremia. Material and Methods: We have conducted a cross-sectional study with a sample involving 126 renal transplant recipients. 126 samples of saliva and 52 samples of blood were collected from these patients. Detection and quantification of BKPyV were performed using a real-time PCR. To compare the presence of BKPyV in blood and saliva, the binomial proportion test was used. To verify associations between salivary shedding BKPyV and post-transplant periods (in months), the Mann-Whitney test was used. Spearman's correlation was used to correlate the viral load in the saliva with blood of kidney transplant recipients. Results: The mean age of the study group was 51.11 +/- 12.45 years old, and 69 participants (54.8%) were female, with a mean post-transplantation time of 4.80 +/- 6.04 months. BKPyV was quantified in several samples of saliva and blood, with medians of 1,108 cp/mL and 1,255 cp/mL, respectively. Only 16/52 (30.8%) participants presented BKPyV in blood, and 59/126 (46.8%) excreted the virus in saliva (p=0.004). BKPyV shedding was found in patients at a shorter post-transplantation period (3.86 +/- 5.25, p=0.100). A weak correlation was observed between viral quantification in saliva and blood (Spearman's correlation coefficient=0.193). Conclusion: The results of this study suggested that, although saliva excretes more BKPyV than blood, there is no reliable correlation between salivary shedding and blood viremia, showing two independent compartments of viral replication.
  • article 9 Citação(ões) na Scopus
    Detection of human polyomaviruses JC and BK in liver pretransplant patients
    (2017) FIGUEIREDO, M. A.; FINK, M. C. Domingues; CASTRO, T.; BRAZ-SILVA, P. H.; STEFFENS, J. C.; EDUARDO, F. P.; GALLOTTINI, M.; ORTEGA, K. L.
    ObjectiveThis study aimed to identify and quantify polyomaviruses (BKPyV and JCPyV) in the saliva, mouthwash, blood and urine of liver pretransplant patients. Materials and MethodsA case-control study was performed using a convenience sample of 21 end-stage liver disease patients (EG=experimental group) and 20 normoreactive controls (CG=control group). In total, 162 samples were collected. Detection and quantification of polyomaviruses were performed using real-time PCR method. ResultsIn the EG, 21 samples (25%) were positive for BKPyV and 10 (11.90%) for JCPyV, while in the CG, 27 samples (34.61%) were positive for BKPyV and six (7.69%) for JCPyV. With regard to the number of samples positive for BKPyV and JCPyV, there was no statistically significant difference between EG and CG (p=.52 and p=.25). In the EG, we observed a panorama similar to that of the CG regarding the presence of polyomaviruses in mouthwash, blood and urine. The greatest difference between the samples was that regarding the identification of BKPyV in saliva. ConclusionCirrhotic patients on the liver transplant waiting list did not show higher prevalence of BKPyV and JCPyV compared to normoreactive controls.
  • article 52 Citação(ões) na Scopus
    Role of Neutralizing Antibodies in Adults With Community-Acquired Pneumonia by Respiratory Syncytial Virus
    (2012) LUCHSINGER, Vivian; PIEDRA, Pedro A.; RUIZ, Mauricio; ZUNINO, Enna; MARTINEZ, Maria Angelica; MACHADO, Clarisse; FASCE, Rodrigo; ULLOA, Maria Teresa; FINK, Maria Cristina; LARA, Pamela; AVENDANO, Luis F.
    Background. Respiratory syncytial virus (RSV) has been implicated in the etiology of adult community-acquired pneumonia (CAP). We investigated RSV infection in Chilean adults with CAP using direct viral detection, real-time reverse-transcription polymerase chain reaction (rtRT-PCR), and serology (microneutralization assay). Methods. RSV, other respiratory viruses, and bacteria were studied by conventional and molecular techniques in adults aged >= 18 years presenting with CAP to the healthcare facilities in Santiago, Chile from February 2005 through December 2007. Results. All 356 adults with CAP enrolled had an acute blood sample collected at enrollment, and 184 had a convalescent blood sample. RSV was detected in 48 cases (13.4%). Immunofluorescence assay and viral isolation each detected only 1 infection (0.2%), whereas rtRT-PCR was positive in 32 (8.9%) cases and serology was positive in 20 (10.8%) cases. CAP clinical characteristics were similar in RSV-infected and non-RSV-infected cases. RSV-specific geometric mean serum-neutralizing antibody titer (GMST) was significantly lower at admission in the 48 RSV-infected cases compared with 308 non-RSV-infected adults (GMST in log(2): RSV/A 8.1 vs 8.9, and RSV/B 9.3 vs 10.4; P < .02). Conclusions. RSV infection is frequent in Chilean adults with CAP. Microneutralization assay was as sensitive as rtRT-PCR in detecting RSV infection and is a good adjunct assay for diagnostic research. High RSV-specific serum-neutralizing antibody levels were associated with protection against common and severe infection. The development of a vaccine could prevent RSV-related CAP in adults.
  • article 12 Citação(ões) na Scopus
    Human polyomaviruses JC and BK in the urine of Brazilian children and adolescents vertically infected by HIV
    (2011) MACHADO, Daisy Maria; FINK, Maria Cristina; PANNUTI, Claudio Sergio; SUCCI, Regina Celia de Menezes; MACHADO, Alessandra Aparecida; CARMO, Fabiana Bononi do; GOUVEA, Aida de Fatima Barbosa; URBANO, Paulo Roberto; BELTRAO, Suenia Vasconcelos; SANTOS, Isabel Cristina Lopes dos; MACHADO, Clarisse Martins
    The aim of this study was to characterize the urinary excretion of the BK (BKV) and JC (JCV) human polyomaviruses in a cohort of human immunodeficiency virus (HIV)-infected children and adolescents. One hundred and fifty-six patients were enrolled: Group I included 116 HIV-infected children and adolescents [median age = 11.4 years (y); range 1-22 y]; Group II included 40 non-HIV-infected healthy controls (median age = 11.37 y; range 7-16 y). Single urine samples from both groups were screened for the presence of JCV and BKV DNA by polymerase chain reaction at enrolment. The overall rate of JCV and BKV urinary excretion was found to be 24.4% and 40.4%, respectively (n = 156). Group I had urinary excretion of JCV and BKV in 27.6% and 54.3% of subjects, respectively. In contrast, Group II showed positive results for JCV in 17.5% of subjects and for BKV in 12.5% of subjects (p Pearson JCV = 0.20; p Pearson BKV < 0.0001). In Group I, there was no association between JCV/BKV shedding and age, gender or CD4 values. Patients with an HIV viral load < 50 copies/mL had a lower excretion of BKV (p < 0.001) and a trend of lower JCV excretion (p = 0.07). One patient in Group I (1/116, 0.9%) showed clinical and radiological features consistent with progressive multifocal leukoencephalopathy, suggesting that children with HIV/polyomavirus coinfection should be kept under surveillance.
  • article 6 Citação(ões) na Scopus
    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.
  • article 7 Citação(ões) na Scopus
    Potential measles transmission risk in mass gatherings: Are we safe for the Olympic games-Rio 2016?
    (2016) NALI, Luiz Henrique da Silva; FUJITA, Dennis Minoru; SALVADOR, Felipe Scassi; FINK, Maria Cristina Domingues da Silva; ANDRADE JR., Heitor Franco de; PANNUTI, Claudio Sergio; LUNA, Expedito Jose de Albuquerque
  • article 9 Citação(ões) na Scopus
    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 de
    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.