PAULO HENRIQUE BRAZ DA SILVA
Projetos de Pesquisa
Unidades Organizacionais
ODE, FO - Docente
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
17 resultados
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- Oral shedding of herpesviruses and clinical outcomes in hematopoietic stem cell transplant patients(2023) MIRANDA-SILVA, Wanessa; MOLLA, Vinicius Campos de; KNEBEL, Franciele Hinterholz; TOZETTO-MENDOZA, Tania Regina; ARRAIS-RODRIGUES, Celso; CAMARGO, Anamaria Aranha; BRAZ-SILVA, Paulo Henrique; FREGNANI, Eduardo RodriguesObjectives To characterize the oral shedding of herpes viruses in patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) and investigate its relationship with clinical outcomes. Materials and Methods Polymerase chain reaction and enzymatic digestion were performed to identify the oral shedding of the members of the Herpesviridae family in 31 patients. The samples were collected from the oral cavity at five timestamps. Results The presence of each herpesvirus in the oral cavity was observed in 3.2%, 12.9%, 19.3%, 32.2%, 54.8% and 93.5% patients for human herpesvirus (HHV)-6A, herpes simplex virus-1, HHV-6B, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and HHV-7, respectively. Oral shedding of herpes virus was not uncommon after alloHSCT. There was a statistically significant association between the EBV and CMV oral shedding at C1 and the cumulative incidence of acute graft-versus-host disease (aGVHD). The results suggested that the presence of HSV-1 at C2 was related to a relapse. The HHV-7 oral shedding at C2 suggests a possible link between relapse, progression-free survival and overall survival of the patients. Conclusions Patients who developed aGVHD showed higher CMV and EBV shedding in the oral cavity at aplasia, suggesting modifications to the pattern of immune cell response and inflammatory microenvironment.
- Torquetenovirus: predictive biomarker or innocent bystander in pathogenesis(2023) TOZETTO-MENDOZA, Tania Regina; BRAZ-SILVA, Paulo Henrique; GIANNECCHINI, Simone; WITKIN, Steven S.
- The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4(+) T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy(2022) HONORATO, Layla; WITKIN, Steven S.; MENDES-CORREA, Maria Cassia; TOSCANO, Ana Luiza Castro Conde; LINHARES, Iara Moreno; PAULA, Anderson Vicente de; PAIAO, Heuder Gustavo Oliveira; PAULA, Vanessa Salete de; LOPES, Amanda de Oliveira; LIMA, Silvia Helena; RAYMUNDI, Vanessa de Cassia; FERREIRA, Noely Evangelista; SILVA JUNIOR, Almir Ribeiro da; ABRAHIM, Karim Yaqub; BRAZ-SILVA, Paulo Henrique; TOZETTO-MENDOZA, Tania ReginaIntroductionTorque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer. MethodsSaliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review. ResultsTTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log(10) TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p < 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p < 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p < 0.0001). ConclusionThe TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.
- Longitudinal study on oral shedding of human betaherpesviruses 6 and 7 in renal transplant recipients reveals active replication(2020) RAPOSO, Jessica Vasques; SARMENTO, Dmitry Jose De Santana; PINTO, Rafaela Barbosa Da Silva; LOPES, Amanda Oliveira; GALLOTTINI, Marina; TOZETTO-MENDOZA, Tania Regina; BRAZ-SILVA, Paulo Henrique; PAULA, Vanessa Salete deBackgroung Roseolovirus latency and persistence in salivary glands that are frequently reactivated after renal transplantation to cause infection have been reported. However, limited information is available on the persistence and excretion of HHV-6 and HHV-7 during and after transplant. Methods 32 renal transplant recipients were followed up before (T1) and after transplant (T2 and T3) and viral replication (via assessment of mRNA) in oral fluid samples investigated. Roseolovirus DNA was detected and quantified via multiplex qPCR. For evaluation of mRNA replication, positive samples were subjected to nested RT-PCR. Results Viral replication of HHV-7 was significantly increased during T3 (72.9%), compared to the pre-transplant period T1 (25%; McNemar Test, p= 0.001). Analysis of the viral replicative to quantitative ratio disclosed ahigher number of DNA copies (>10(6)) in positive cases of replication (p < 0.001). Astrong positive correlation (Spearman correlation coefficient = 0.781; p< 0.001) was evident between viral quantities of Roseoloviruses. Conclusion Our findings consistently suggest that the salivary gland is an important site of active and persistent infection by roseoloviruses. In view of the increasing problem of Roseoloviruses, pre- and post-transplantation, viral surveillance and monitoring of active replication are pivotal steps for effective screening and treatment of renal transplant patients.
- Introduction of human gammaherpesvirus 8 genotypes A, B, and C into Brazil from multiple geographic regions(2020) LOPES, Amanda de Oliveira; SPITZ, Natalia; MARTINELLI, Katrini Guidolini; PAULA, Anderson Vicente de; TOSCANO, Ana Luiza de Castro Conde; BRAZ-SILVA, Paulo Henrique; BARBOSA NETTO, Juliana dos Santos; TOZETTO-MENDOZA, Tania Regina; PAULA, Vanessa Salete deVariations in the open reading frame (ORF) K1 gene sequence of human gammaherpesvirus 8 (HHV-8) has led to the identification of 6 major genotypic clades (A, B, C, D, E, and F) in specimens isolated from around the world. These clades exhibit clear clustering among individuals in different ethnic groups and from different geographic regions. The human population of Brazil varies greatly in ethnicity because of multiple immigration events from Africa, Europe, Asia, and indigenous communities. However, there is scant information about the HHV-8 genotypes currently circulating in Brazil. Here, we describe HHV-8 genotypic diversity in isolates from Brazilian HIV-infected patients living with Kaposi's sarcoma (KS) by analysis of the complete ORF-K1 region. We also identified the most likely geographic origins of these different Brazilian genotypes. We extracted HHV-8 DNA (24 positive samples) from individuals with HIV/KS from the states of Sao Paulo and Rio de Janeiro, amplified the ORF-K1 gene using nested PCR (about 870 base pairs), performed sequencing and phylogenetic analysis, and then calculated the mean genetic distances of Brazilian sequences from sequences in other regions of the world (523 sequences analyzed). Phylogenetic analysis showed that genotypes C, A, and B were present in 45.8 %, 29.2% and 25 % of the isolates from Brazil, respectively. These isolates grouped into separate clades, rather than a single monophyletic cluster. Mean genetic distance analyses suggested that these genotypes were introduced into the Brazil multiple times from different geographical regions. HHV-8/A isolates appear to be from Ukraine, Russia, and the Tartar ethnic group; HHV-8/B isolates appear to be from Congo and Democratic Republic of the Congo; and HHV-8/C isolates appear to be from Australia, Algeria, England, and French Guiana. These results contribute to a better understanding of the genetic diversity and origins of HHV-8 strains circulating in Brazil, and will provide a foundation for further epidemiological and evolutionary studies of HHV-8.
- 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 HenriqueObjectives: 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.
- Salivary shedding of herpesviruses in renal transplant recipients(2018) SARMENTO, Dmitry Jose de Santana; CALIENTO, Rubens; SOUZA, Amabile Oliveira de; TOZETTO-MENDOZA, Tania Regina; PALMIERI, Michelle; MARTINS, Victor Adriano de Oliveira; BRAZ-SILVA, Paulo Henrique; GALLOTTINI, MarinaAim The aim of the present study was to describe the salivary shedding of human herpesviruses (HHV) in renal transplant recipients and to observe the oral manifestations in this group. Methods A prospective case-control study was conducted with a study group of 20 renal transplant recipients and a control group of 20 non-transplanted, immunocompetent individuals. Clinical examination evaluated the presence of drug-induced gingival overgrowth (DIGO), salivary flow, and caries. Stimulated saliva was collected from both groups, with HHV being detected by using real-time polymerase chain reaction. Results The mean age of the study group was 45.90 +/- 9.89 years, with 55% (11/20) being female, 60% (12/20) being Caucasian, 65% (13/20) having a deceased donor, and 70% (14/20) having used tacrolimus as the main immunosuppressive drug. Renal transplant recipients had shedding of more herpesviruses compared to the control group, with the exception of HHV-7. Statistical significance was found for herpes simplex virus-1 (HSV-1) (P = 0.017) and cytomegalovirus (P = 0.035). DIGO was observed in seven patients (35%), with 35% (7/20) presenting with decreased salivary flow and four (20%) reporting xerostomia. Conclusion Renal transplant recipients excreted herpesviruses more often than control individuals, especially HSV-1. Decreased salivary flow and xerostomia were more frequent in patients who used tacrolimus, whereas those who used cyclosporine had more cases of DIGO.
- Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma Is genotype B associated with better prognosis of AIDS-KS?(2016) TOZETTO-MENDOZA, Tania Regina; IBRAHIM, Karim Yaqub; TATENO, Adriana Fumie; OLIVEIRA, Cristiane Mendes de; SUMITA, Laura Massami; SANCHEZ, Maria Carmem Arroyo; LUNA, Expedito Jose; PIERROTTI, Ligia Camara; DREXLER, Jan Felix; BRAZ-SILVA, Paulo Henrique; PANNUTI, Claudio Sergio; ROMANO, Camila MaltaAIDS-associated Kaposi's sarcoma (AIDS-KS) caused by human herpes virus 8 (HHV-8) is the most severe and resistant form of KS tumor. Our aim was to verify whether there is an association between HHV-8 variability and development of AIDS-KS in Brazil by comparing the HHV-8 variability between individuals without and with KS. Saliva samples and blood, when available, were analyzed by PCR techniques for detection of the fragments of ORF K1 of HHV-8, which were then genotyped and analyzed regarding the genetic variability. Our study described 106 positive cases for HHV-8 in the saliva from 751 AIDS patients without previous KS. In addition, we performed a phylogenetic analysis of HHV-8 in 34 of the 106 AIDS patients without KS and in 33 of the 37 patients with active KS. The distribution of HHV-8 genotypes A, B, C, and F in AIDS individuals was indistinguishable by comparing non-KS and KS groups, as well as regarding ethnicity. Considering the KS group, genotype B was associated with better prognosis of KS tumor. Interestingly. we found a particular profile of diversity within Glade C and 2 recombinant patterns of HHV-8 in the saliva of AIDS individuals without KS. We emphasize the need to achieve standard genotyping protocol for ORF K1 amplification, thus allowing for substantial detection of HHV-8 variants. Our findings can shed light on the role of HHV-8 variability in the pathogenesis of AIDS-KS.
- Oral shedding of human herpesviruses in renal transplant recipients(2018) SARMENTO, Dmitry Jose de Santana; TOZETTO-MENDOZA, Tania Regina; SUMITA, Laura Masami; PIERROTI, Ligia Camara; PALLOS, Debora; CALIENTO, Rubens; PALMIERI, Michelle; MARTINS, Victor Adriano de Oliveira; GALLOTTINI, Marina; PANNUTI, Claudio Sergio; BRAZ-SILVA, Paulo HenriqueTo describe the shedding profile of human herpesviruses in the saliva of renal transplant recipients. This is a prospective case-control study of 50 renal transplant recipients and control group of 50 individuals (non-transplanted and immunocompetent). Mouthwash samples were collected via oral rinse and then submitted to screening for the presence of eight types of herpesviruses by using multiplex PCR. Fisher's exact, chi-square, and Student t tests were used for statistical analysis, and the significance level was set at 5%. The mean age of the study group was 49.42 +/- 12.94 years, 28/50 (56%) were female, and the time elapsed after transplantation was 68.20 +/- 67.19 months. Herpes simplex virus 1 (HSV-1) (P = 0.025) and Epstein-Barr virus (EBV) (P = 0.024) were, statistically, more excreted in the saliva of renal transplant recipients compared to control group. Gender (P = 1.00) and age (P = 0.563) did not influence the salivary shedding of herpesviruses in renal transplant recipients. Individuals who excreted varicella-zoster virus in saliva had a shorter mean time of transplantation (22:00 + 2.82 months) (P < 0.001). Renal transplant recipients excreted herpesviruses more often than controls, especially HSV-1 and EBV, with salivary shedding of herpesviruses being more frequent in patients with recent kidney transplantation. The present findings support other longitudinal studies evaluating the relationship between oral shedding of human herpesviruses and clinical presence of active infection and renal transplant failure.
- Torquetenovirus in saliva: A potential biomarker for SARS-CoV-2 infection?(2021) MENDES-CORREA, Maria C.; TOZETTO-MENDOZA, Tania Regina; FREIRE, Wilton S.; PAIAO, Heuder G. O.; FERRAZ, Andrea B. C.; MAMANA, Ana C.; FERREIRA, Noely E.; V, Anderson de Paula; FELIX, Alvina C.; ROMANO, Camila M.; BRAZ-SILVA, Paulo H.; LEAL, Fabio E.; GRESPAN, Regina M. Z.; SABINO, Ester C.; COSTA, Silvia F.; WITKIN, Steven S.Torquetenovirus (TTV) is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants. We assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status. Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group. The saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2-4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved. We propose that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis.