Evaluation of the cervicovaginal environment in asymptomatic Human T-cell lymphotropic virus type 1 infected women

ABSTRACT Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) is sexually transmitted and causes persistent infection. This virus induces activation of the immune system and production of inflammatory cytokines. This study aimed to assess the cytokine profile and cytopathological findings in the cervicovaginal fluid of asymptomatic HTLV-1-infected women. Methods: HTLV-1-infected and uninfected women were selected at the Centro de Atendimento ao Portador de HTLV in Salvador-Brazil. None of the included HTLV-1-infected women reported any HTLV-1-associated diseases. All volunteers underwent gynecological examination to collect cervicovaginal fluid. Cytokine quantification was performed using the Cytometric Bead Array (CBA) Human Th1/Th2/Th17 kit. Light microscopy was used to evaluate cervicovaginal cytopathology. In addition, proviral load in cervicovaginal fluid and peripheral blood was measured by real-time quantitative polymerase chain reaction. Results: 112 women (63 HTLV-1-infected and 49 uninfected) were evaluated. No differences were found with respect to cytopathological cervicovaginal findings between the groups. IL-2, TNF, IL-4, IL-10, and IL-17 levels were significantly higher in cervicovaginal fluid of the HTLV-1-infected women than in uninfected women (p < 0.05). Conversely, IFN-γ was found to be lower in the HTLV-1-infected women (p < 0.001) compared to uninfected individuals. Cervicovaginal proviral load was detectable in 53% of the HTLV-1-infected women and was found to be consistently lower than the proviral load in peripheral blood. Conclusions: HTLV-1 infection induces immune activation in cervicovaginal environment, characterized by elevated concentrations of Th1, Th2, and IL17 in the cervicovaginal fluid.

A novel association of BoLA DRB3 alleles in BLV infected cattle with different proviral loads / Uma nova associação de alelos de BoLA DRB3 em bovinos infectados com BLV com diferentes cargas provirais

Bovine leukemia virus (BLV) is associated with the most common neoplastic disease of cattle. BLV has a silent dissemination in the herd due to infected cell exchange, thus the concentration of BLV-infected cells in blood should play a major role in the success of viral transmission. Genes from Bovine leukocyte antigen (BoLA), the MHC system of cattle, are associated with genetic resistance and susceptibility to a wide range of diseases, and also with production traits. Some BoLA DRB3.2 allele polymorphisms in Holstein cattle have been associated with resistance or susceptibility to BLV-disease development, or with proviral load (PVL). This investigation studied 107 BLV-infected Argentinean Holstein dairy cows, all of them belonging to one herd. PVL was analysed by qPCR and animals were classified as high proviral load (HPVL, N = 88) and low proviral load (LPVL, N = 19), and BoLA DRB3.2 alleles were genotyped. Alleles BoLA DRB3.2*1501 and *1201 were significantly associated with HPVL (p = 0.0230 and p = 0.0111 respectively), while allele BoLA DRB3.2*0201 was significantly associated with LPVL (p = 0.0030). The present study aims at contributing to the knowledge of the association between BoLA polymorphism and development of a BLV infection profile. Genes that best explain the PVL in this population resulted BoLA DRB3.2*0201 (as a protection factor) and *1501 (as a risk factor). Allelic differences may play an important role in the development of effective immune responses. A better understanding of how BoLA polymorphism contributes to these responses and the establishment of a BLV status is desirable to schedule and evaluate control measures.(AU)

O vírus da leucemia bovina (BLV) está associado à doença neoplásica mais comum do gado bovino. O BLV tem uma disseminação silenciosa no rebanho devido à troca de células infectadas, assim, a concentração de células BLV infectadas no sangue deve desempenhar um papel importante no sucesso da transmissão viral. Os genes do antígeno leucocitário bovino (BoLA), sistema MHC do gado bovino, estão associados à resistência genética e à susceptibilidade a uma ampla gama de doenças, bem como às características da produção. Alguns polimorfismos de alelos de BoLA DRB3.2 em bovinos Holstein têm sido associados à resistência ou susceptibilidade ao desenvolvimento da doença BLV, ou com carga proviral (PVL). Esta investigação avaliou 107 vacas leiteiras da raça Holstein argentina infectadas com BLV e pertencentes a um único rebanho. A PVL foi analisada por qPCR, os animais foram classificados em alta carga proviral (HPVL, N = 88) e baixa carga proviral (LPVL, N = 19), e os alelos BoLA DRB3.2 foram genotipados. Os alelos BoLA DRB3.2*1501 e *1201 estavam significativamente relacionados à HPVL (p = 0,0230 e p = 0,0111, respectivamente), enquanto o alelo BoLA DRB3.2*0201, à LPVL (p = 0,0030). O objetivo deste estudo é contribuir para o conhecimento da associação entre o polimorfismo de BoLA e o desenvolvimento de infecção por BLV. Os genes que melhor explicam a PVL na população analisada resultaram em BoLA DRB3.2*0201 (como fator de proteção) e *1501 (como fator de risco). As diferenças alélicas podem desempenhar um papel importante no desenvolvimento de respostas imunitárias eficazes. Uma melhor compreensão de como o polimorfismo BoLA contribui para estas respostas e o estabelecimento de um estado BLV é desejável para agendar e avaliar as medidas de controle.(AU)

Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of ATLL patients

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with very poor prognosis and short survival, caused by the human T-lymphotropic virus type-1 (HTLV-1). The HTLV-1 biomarkers trans-activator x (TAX) and HTLV-1 basic leucine zipper factor (HBZ) are main oncogenes and life-threatening elements. This study aimed to assess the role of the TAX and HBZ genes and HTLV-1 proviral load (PVL) in the survival of patients with ATLL. METHODS: Forty-three HTLV-1-infected individuals, including 18 asymptomatic carriers (AC) and 25 ATLL patients (ATLL), were evaluated between 2011 and 2015. The mRNA expression of TAX and HBZ and the HTLV-1 PVL were measured by quantitative PCR. RESULTS: Significant differences in the mean expression levels of TAX and HBZ were observed between the two study groups (ATLL and AC, P=0.014 and P=0.000, respectively). In addition, the ATLL group showed a significantly higher PVL than AC (P=0.000). There was a significant negative relationship between PVL and survival among all study groups (P=0.047). CONCLUSION: The HTLV-1 PVL and expression of TAX and HBZ were higher in the ATLL group than in the AC group. Moreover, a higher PVL was associated with shorter survival time among all ATLL subjects. Therefore, measurement of PVL, TAX, and HBZ may be beneficial for monitoring and predicting HTLV-1-infection outcomes, and PVL may be useful for prognosis assessment of ATLL patients. This research demonstrates the possible correlation between these virological markers and survival in ATLL patients.

Analysis of env Subtypes of Porcine Endogenous Retrovirus in SNU Miniature Pigs

All xenografts from pigs impose infection risk by porcine endogenous retrovirus (PERV). The purpose of this study was to investigate the env constructs with the comparison of the ratio of the competent form to the defective one of env in subtypes, PERV-A, PERV-B and PERV-C in different pig breeds. The results of PCR amplification of env represented that all env subtypes had more than two defective forms which cannot bind to host cells due to the absence of binding regions of env in miniature pigs, SNU and PWG, and farm pig breeds, Duroc, Yorkshire and Landrace. In addition, comparing the full sequences with the defective ones in three subtypes demonstrated that the present percentages of env sequences in defective PERV-A, PERV-B and PERV-C were approximately 50%, 38~45% and 4~11%, respectively, in SNU and PWG pigs whereas PERV-A and PERV-B occupied around 40 to 60% but PERV-C was not detected in farm pigs. Quantitative real-time PCR assays with primers and probes targeted to proline-rich region (PRR) of each env subtype were done to measure the copy numbers of each env subtype. When the reference was set with copy number of PERV-A, the ratio of those of PERV-B and PERV-C to the reference were 1.5 to 6.0 folds high in SNU and PWG pigs while 1.0 or less in farm pigs. These contradictory results of PERV-C constructs and copy numbers in SNU pigs suggests that many truncated or short defective sequences of PERV-C might be present in them.

Perfil de ativação dos linfócitos T de pacientes com mielopatia associada ao vírus linfotrópico das células T humanas do tipo 1 (HTLV-1) / paraparesia tropical espástica (HAM/TSP) possível, provável e definido / Activation profile of T lymphocytes of patients with myelopathy associated with human T-lymphotropic virus type 1 cells (HTLV-1) tropical spastic paraparesis (HAM / TSP) possible, probable and definite

O vírus linfotrópico das células T humanas do tipo 1 (HTLV-1) é o agente etiológico da mielopatia associada ao HTLV / paraparesia espástica tropical (HAM / TSP ), que ocorre em menos de 5 % dos indivíduos infectados. A resposta imune controla parcialmente a infecção, porém pode estar ligada a patogênese da doença. O objetivo deste estudo foi caracterizar fenotipicamente as subpopulações de linfócitos T, em pacientes assintomáticos e com diagnóstico de HAM/TSP. Foram avaliados 103 pacientes acompanhados no Centro de HTLV da Escola Bahiana de Medicina e Saúde Pública (EBMSP) e 19 controles não infectados. Os pacientes foram categorizados de acordo com o grau de certeza do diagnóstico de HAM/TSP: possível (Ps), provável (Pb) e definido (D), além de pacientes assintomáticos (ASS). O perfil fenotípico (CD25, CD45RA, CD45RO, HLA-DR, CD25, CCR-7, CD62L)...

The human T-cell lymphotropic vírus type 1(HTLV-1) is the etiological agent of HTLV- associated myelopathy/ Tropical spastic paraparesis(HAM/TSP), wich occurs in less then 5% of the infected individuals. The immune response partially controls the infection, but may be linked to the pathogenesis of disease. The aim of this study was to characterize phenotipically T lymphocyte subpopulations in asymptomatic and in patients diagnosed with HAM/TSP. We evaluated 103 patients treated at the center for HTLV of Bahia School of Medicine and Public Health (EBMSP) and 19 uninfected controls. Patients were categorized as asymptomatic and according to the degree of certainty of the diagnosis of HAM/TSP: Possible(Ps), Probable(Pb) and Definite(D). The phenotypic profile (CD25, CD45RA, CD45RO, HLA-DR, CCR-7, CD62L)...

Evolution of HTLV-1 proviral load in patients from Salvador, Brazil

INTRODUCTION: Variations in human T cell lymphotropic virus type 1 (HTLV-1) proviral load (PVL) in infected individuals over time are not well understood. Objective: To evaluate the evolution of proviral load in asymptomatic individuals and HAM/TSP patients in order to help determine periodicity for measuring proviral load. METHODS: A group of 104 HTLV-1 infected patients, followed at the HTLV reference center in Salvador, Brazil, were included in the study (70 asymptomatic and 34 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients). HTLV-1 PVL was measured using real-time polymerase chain reaction (PCR) at baseline and again at another point, either < 12 months, between 12-24 months, or > 24 months. RESULTS: HAM/TSP patients had higher PVL (ranging from 11,041 to 317,009 copies/10(6) PBMC) when compared to asymptomatic individuals (ranging from 0 to 68,228 copies/10(6) PBMC). No statistically significant differences were observed in the medians of PVL in HAM/TSP patients or asymptomatic individuals over time. However, in asymptomatic individuals with a PVL below 50,000 copies/10(6) PBMC, a statistically significant two-fold increase was observed over time. CONCLUSION: HTLV-1-PVL remained stable in both asymptomatic individuals and HAM/TSP patients over time. Frequent monitoring of asymptomatic individuals with low PVLs is recommended and further studies should be conducted to assess the course of PVL in these patients over extended periods of time.

Evidence of a higher prevalence of HPV infection in HTLV-1-infected women: a cross-sectional study / Evidência de maior prevalência de infecção pelo HPV em mulheres infectadas pelo HTLV-1: um estudo de corte transversal

INTRODUCTION:HTLV-1 infection increases susceptibility to other infections. Few studies have addressed the co-infection between HPV and HTLV-1 and the immune response involved in this interaction. The aim of this study was to determine the prevalence of cervical HPV infection in HTLV-1-infected women and to establish the risk factors involved in this co-infection. METHODS: A cross-sectional study was carried out in Salvador, Brazil, between September 2005 and December 2008, involving 50 HTLV-1-infected women from the HTLV Reference Center and 40 uninfected patients from gynecological clinic, both at the Bahiana School of Medicine. HPV infection was assessed using hybrid capture. HTLV-1 proviral load was quantified using real-time polymerase chain reaction (PCR). RESULTS: The mean age of HTLV-1-infected women (38 ± 10 years) was similar to that of the control group (36 ± 13 years). The prevalence of HPV infection was 44% in the HTLV-1-infected group and 22.5% in uninfected women (p = 0.03). HTLV-1-infected women had lower mean age at onset of sexual life (17 ± 3 years versus 19 ± 3 years; p = 0.03) and greater number of lifetime partners compared with the control group (4 ± 3 versus 2 ± 1; p < 0.01). In the group of HTLV-1-infected patients, there was neither difference in HTLV-1 proviral load between HPV-infected women and the uninfected. CONCLUSIONS: The prevalence of HPV infection was higher in HTLV-1-infected women. Further studies should be performed to evaluate the progression of this co-infection.

INTRODUÇÃO:A infecção pelo HTLV-1 aumenta a susceptibilidade para outras infecções. Poucos estudos avaliaram a co-infecção entre HPV/HTLV-1 e a resposta imune envolvida nesta interação. O objetivo deste trabalho é determinar a prevalência de infecção cervical pelo HPV em mulheres infectadas pelo HTLV-1 e estabelecer os fatores de risco envolvidos nesta co-infecção. MÉTODOS: Um estudo de corte transversal foi conduzido em Salvador, Brasil, entre setembro de 2005 e dezembro de 2008, envolvendo 50 mulheres infectadas pelo HTLV-1, acompanhadas no Centro de Referência de HTLV e 40 mulheres não infectadas, acompanhadas no Serviço de Ginecologia, ambos na Escola Bahiana de Medicina. A infecção pelo HPV foi confirmada pela Captura Híbrida. A carga proviral do HTLV-1 foi quantificada pelo PCR em tempo real. RESULTADOS: A média de idade das mulheres infectadas pelo HTLV-1 (38±10 anos) foi semelhante ao do grupo controle (36±13 anos). A prevalência de infecção pelo HPV foi 44% nas mulheres infectadas pelo HTLV-1 e de 22,5% no grupo controle (p=0,03). Mulheres infectadas pelo HTLV-1 informaram menor idade de início de vida sexual (17±3 anos versus 19±3 anos; p=0,03) e maior número de parceiros sexuais, em relação ao grupo controle (4±3 versus 2±1; p<0,01). No grupo de mulheres infectadas pelo HTLV-1, não se observou diferença entre a carga proviral do HTLV-1 entre as mulheres infectadas pelo HPV e as não infectadas. CONCLUSÕES: A prevalência de infecção pelo HPV foi maior em mulheres infectadas pelo HTLV-1. Novos estudos devem ser realizados para avaliar a progressão desta co-infecção.