TANIA REGINA TOZETTO MENDOZA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
44 resultados
Resultados de Busca
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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.
- Association of NF kappa B and related-cytokines with the viral load and development of antibodies against HHV-8 in people living with HIV/AIDS(2020) GONCALES, Juliana Prado; LOPES, Thaisa Regina Rocha; LORENA, Virginia Maria Barros de; ACIOLE, Melayne Rocha; SILVA JUNIOR, Jose Valter Joaquim; TOZETTO-MENDOZA, Tania Regina; BRAZ-SILVA, Paulo Henrique; COELHO, Maria Rosangela Cunha DuarteHuman gammaherpesvirus 8 (HHV-8) replication is influenced by a complex interaction between viral and host elements. Here, we evaluated the expression of NF kappa B and TNF-alpha in B (CD19 +) and T (CD3 +) lymphocytes, and the serum concentration of IL-1 beta and IL-12 cytokines in people living with HIV/AIDS (PLHA), negative for HHV-8-related diseases, and who presented antibodies to latent or lytic antigens from HHV-8. In addition, we also evaluated the correlation of HHV-8 viral load with NF kappa B, TNF-alpha, IL-1 beta and IL-12 levels. The expression of NF kappa B (p < 0.0001) or TNF-alpha (p < 0.0001) in B lymphocytes (CD19 +) and the IL-1 beta (p < 0.0266) and IL-12 (p < 0.0001) concentrations were associated with the presence of antibodies to HHV-8 lytic antigens. The CD19 + NF kappa B + TNF-alpha + and CD3 + NF kappa B + TNF-alpha + cells were also associated with the presence of antibodies to lytic infection (p < 0.0001). Among all PLHA evaluated, only individuals with the highest titers of lytic antibodies, i.e., 1:320, had detectable HHV-8 viral load. In these, HHV-8 viral load was correlated to NF kappa B (r = 0.6, p = 0.003) and TNF-alpha (r = 0.5, p = 0.01) (both in CD19 + lymphocytes) and with IL-1 beta (r = 0.5, p = 0.01) and IL-12 (r = 0.6, p = 0.006) levels. We believe that viral replication and/or reactivation, in addition to being associated with the development of lytic antibodies against HHV-8, may be associated with inflammatory response via NF kappa B. Finally, although immune response imbalance has been previously related to HHV-8-associated diseases, our results indicate that important changes in immunity, mainly in the inflammatory response, may be clearly observed in individuals with HHV-8, but who have not yet presented clinical manifestations.
- 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.
- Concentration of cytokines in patients with osteoarthritis of the knee and fibromyalgia(2014) IMAMURA, Marta; TARGINO, Rosa Alves; HSING, Wu Tu; IMAMURA, Satiko; AZEVEDO, Raymundo Soares; BOAS, Lucy Santos Villas; TOZETTO-MENDOZA, Tania Regina; ALFIERI, Fabio Marcon; FILIPPO, Thais Raquel; BATTISTELLA, Linamara RizzoIntroduction: Fibromyalgia and osteoarthritis may present a relationship with the -concentration of cytokines. The aim of this study was to compare the serum concentrations of IL-12p70, tumor necrosis factor, IL-10, IL-6, IL-1 beta, and IL-8 in patients with knee osteoarthritis and fibromyalgia. Materials and methods: The study included 53 women (71.2 +/- 7.6 years old) diagnosed with knee osteoarthritis with moderate-to-severe pain (visual analog scale. 4) for at least 3 months. Sixty women (54.1 +/- 8.1 years old) diagnosed with fibromyalgia according to the American College of Rheumatology criteria and with moderate-to-severe pain (visual analog scale. 4) also participated in this study. For the dosage of cytokines, blood was collected in the morning: 5 mL from the cubital vein. The material was centrifuged at 4 degrees C, separated into 100 mu L aliquots and stored at -80 degrees C until processing. Serum concentrations of the studied cytokines were assessed using the BD Cytometric Bead Array method. Data were analyzed with Student's t-test and the Mann-Whitney U test. Results: We found higher levels of IL-6, IL-10, and IL-1 beta in fibromyalgia patients. After adjustment of age as a covariate, there was no statistically significant difference in the concentration of any cytokine between fibromyalgia and knee osteoarthritis patients. Conclusion: Patients with knee osteoarthritis and fibromyalgia with the same duration and intensity of pain demonstrate similar concentrations of cytokines. Aging may play a role in cytokine profile, a finding not so extensively addressed in the literature and one that should be further investigated.
- 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.
- Association between torquetenovirus in vaginal secretions and infertility: An exploratory metagenomic analysis(2023) COSTA, A. Charlys Da; BORTOLETTO, Pietro; SPANDORFER, Steven D.; TOZETTO-MENDOZA, Tania Regina; LINHARES, Iara M.; MENDES-CORREA, Maria Cassia; WITKIN, Steven S.ProblemThe association of viruses with infertility remains incompletely evaluated.Method of studyVaginal secretions from 46 women seeking treatment in the Center for Reproductive Medicine and Infertility at Weill Cornell Medicine were tested for viruses by metagenomic analysis by lab personnel blinded to all clinical data.ResultsTorquetenovirus (TTV) was identified in 16 women, alphapapillomavirus in seven women and most were positive for bacteriophages. Twelve of the subjects were fertile and sought to freeze their oocytes for future implantation. These women were all negative for TTV. In contrast, 16 of the 34 women (47.1%) being treated for infertility were TTV-positive (p = .0035). Evaluating the women by cause of infertility, five of nine women (55.6%) whose male partner had inadequate sperm parameters and six of 14 women (42.9%) with defective ovulation were TTV positive (p = .0062 and p = .0171, respectively, vs. the fertile women). Alphapapillomavirus was identified in one (8.3%) fertile woman, five (35.7%) women with ovulation deficiency, and one (11.1%) woman with male factor infertility. These differences were not statistically significant. There were no differences in bacteriophage families or the presence of Lactobacillus phages between fertile or infertile women or between different causes of infertility. There was a negative association between TTV detection and Lactobacillus crispatus dominance in the vaginal microbiota (p = .0184), but no association between TTV detection and the presence of alphapapillomavirus or Candida species.ConclusionDetection of TTV in the vagina might be a biomarker for specific causes of infertility.
- 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.
- Potential effect of Zika virus infection on human male fertility?(2018) AVELINO-SILVA, Vivian Lida; ALVARENGA, Conrado; ABREU, Carolina; TOZETTO-MENDOZA, Tania Regina; CANTO, Cynthia Liliane Motta do; MANULI, Erika Regina; MENDES-CORREA, Maria Cassia; SABINO, Ester Cerdeira; FIGUEIREDO, Walter Manso; SEGURADO, Aluisio Cotrim; MAYAUD, PhilippeBackground: Zika virus (ZIKV) sexual transmission and prolonged viral shedding in semen have been previously reported, suggesting a strong viral affinity for genital tissues. A transient impact of ZIKV on male fertility was shown in animal and human studies. Methods: Adult male patients with confirmed ZIKV infection diagnosed in the city of Araraquara, Brazil during the epidemic season of 2016 were invited one year after the acute infection to respond to a questionnaire of genital symptoms and to provide a semen sample for molecular ZIKV testing and spermogram analysis, as well as a serum sample for hormonal testing. Results: 101 of 187 tested patients had positive ZIKV RT-PCR in plasma and/or urine samples (54%. 72 women and 29 men). Of 15 adult male participants for whom telephone contact was successful, 14 responded to the questionnaire of genital symptoms and six consented to provide a semen sample at a median of 12 months after the acute infection. We report abnormal spermogram results from patients one year after confirmed ZIKV infection. Conclusions: Our findings suggest a possible long-term detrimental effect of ZIKV infection on human male fertility that has to be further explored in well-characterized samples from cohort studies conducted in ZIKV-endemic areas.
- 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.