Effectiveness assessment of a home-based exercise intervention in mitigating HTLV-1 associated disabilities: A validation study.

To evaluate the effectiveness of a home exercise program called Home Exercise Booklet for People Living with Human T Lymphotropic Virus 1 (HTLV-1). This is a methodological study of content validation with expert judges. A questionnaire with a Likert scale was applied, containing 16 items referring to the content domain. Descriptive statistics were used to obtain the content validity index. In total, 46 judges participated, 24 physiotherapists (PG) and 22 professionals from other health areas specializing in methodological studies and HTLV-1 (EG). In the validation process, each evaluator judged the technology and scored their considerations. In the end, we obtained the following results for the Content Validity Index (CVI): PG CVI: 94.3%, GE CVI: 93.4%. Although the index was sufficient to consider the technology validated, modifications were made to the second and final version of the booklet, considering the judges' observations and suggestions, which we consider relevant. The technology proved to be valid for use with the target audience. The development and validation of this product provides support to help prevent functional decline in people living with HTLV-1; standardize guidelines for physiotherapy professionals who monitor these issues; start a home exercise program aimed at other comorbidities; open the possibility of creating and validating home exercise programs with other comorbidities.

Prevalence and circulant genotypes of Chlamydia trachomatis in university women from cities in the Brazilian Amazon.

BACKGROUND: Approximately 80% of infected women infected by Chlamydia trachomatis are asymptomatic, although this infection can lead to serious complications in the female reproductive tract. Few data on Chlamydia infection and genotypes are available in Amazonian communities. OBJECTIVES: To describe the prevalence of and associated factors and to identify the genotypes of sexual C. trachomatis infection in female university students in different urban centers (capital and interiors) in the Brazilian state of Pará, in the eastern Amazon region. METHODS: A cross-sectional study was performed among young women attending public universities in four different urban centers in the eastern Amazon region. They were invited to participate in the studt and cervical secretions were collected for molecular diagnosis of C. trachomatis. We utilized amplification of the ompA gene by nested PCR. Positive samples were genotyped by nucleotide sequencing. Study participants completed a questionnaire on social, epidemiological, and reproductive health variables. A Qui-square and Binominal regression test were used to evaluate the degree of association of these variables with the infection. RESULTS: A total of 686 female students was included in the study. The overall prevalence of C. trachomatis was 11.2% (77/686). The prevalence of this infection was higher in interiors (15.2% vs 9.5%/ p: 0.0443). Female university students who do not have a sexual partner (11.8%/p <0.008), who do not use a condom in their sexual relations (17.8%/p <0.0001) and who reported having suffered a miscarriage (32%/p <0.0001) have high chances of acquiring this sexual infection. The ompA gene was sequenced in only 33 (42.8%) samples, revealing the genotype J was the most frequent (27.2% [9/33]), followed by genotypes D (24.2% [8/33]), and then genotypes F (18.2% [6/33]), E (15.1% [5/33]) K (6.1% [2/33]), Ia (6.1% [2/33]), and G (3.1% [1/33]). CONCLUSIONS: The high prevalence of sexual infection by C. trachomatis in the female university students from the interior of the state of Pará, individuals with no fixed sexual partner, those that had had a miscarriage, the students that do not use condoms in their sexual relations. The genotype J of C. trachomatis genotypes was the most frequent. These data are important to help defining the epidemiological effects of chlamydial infections in Amazonian populations.

New Perspectives about Drug Candidates Targeting HTLV-1 and Related Diseases.

Among the human T-lymphotropic virus (HTLV) types, HTLV-1 is the most prevalent, and it has been linked to a spectrum of diseases, including HAM/TSP, ATLL, and hyperinfection syndrome or disseminated strongyloidiasis. There is currently no globally standard first-line treatment for HTLV-1 infection and its related diseases. To address this, a comprehensive review was conducted, analyzing 30 recent papers from databases PubMed, CAPES journals, and the Virtual Health Library (VHL). The studies encompassed a wide range of therapeutic approaches, including antiretrovirals, immunomodulators, antineoplastics, amino acids, antiparasitics, and even natural products and plant extracts. Notably, the category with the highest number of articles was related to drugs for the treatment of ATLL. Studies employing mogamulizumab as a new perspective for ATLL received greater attention in the last 5 years, demonstrating efficacy, safe use in the elderly, significant antitumor activity, and increased survival time for refractory patients. Concerning HAM/TSP, despite corticosteroid being recommended, a more randomized clinical trial is needed to support treatment other than corticoids. The study also included a comprehensive review of the drugs used to treat disseminated strongyloidiasis in co-infection with HTLV-1, including their administration form, in order to emphasize gaps and facilitate the development of other studies aiming at better-directed methodologies. Additionally, docking molecules and computer simulations show promise in identifying novel therapeutic targets and repurposing existing drugs. These advances are crucial in developing more effective and targeted treatments against HTLV-1 and its related diseases.

Transmission dynamics of SARS-CoV-2 variants in the Brazilian state of Pará.

Introduction: After three years since the beginning of the pandemic, the new coronavirus continues to raise several questions regarding its infectious process and host response. Several mutations occurred in different regions of the SARS-CoV-2 genome, such as in the spike gene, causing the emergence of variants of concern and interest (VOCs and VOIs), of which some present higher transmissibility and virulence, especially among patients with previous comorbidities. It is essential to understand its spread dynamics to prevent and control new biological threats that may occur in the future. In this population_based retrospective observational study, we generated data and used public databases to understand SARS-CoV-2 dynamics. Methods: We sequenced 1,003 SARS-CoV-2 genomes from naso-oropharyngeal swabs and saliva samples from Pará from May 2020 to October 2022. To gather epidemiological data from Brazil and the world, we used FIOCRUZ and GISAID databases. Results: Regarding our samples, 496 (49.45%) were derived from female participants and 507 (50.55%) from male participants, and the average age was 43 years old. The Gamma variant presented the highest number of cases, with 290 (28.91%) cases, followed by delta with 53 (5.28%). Moreover, we found seven (0.69%) Omicron cases and 651 (64.9%) non-VOC cases. A significant association was observed between sex and the clinical condition (female, p = 8.65e-08; male, p = 0.008961) and age (p = 3.6e-10). Discussion: Although gamma had been officially identified only in December 2020/January 2021, we identified a gamma case from Belém (capital of Pará State) dated May 2020 and three other cases in October 2020. This indicates that this variant was circulating in the North region of Brazil several months before its formal identification and that Gamma demonstrated its actual transmission capacity only at the end of 2020. Furthermore, the public data analysis showed that SARS-CoV-2 dispersion dynamics differed in Brazil as Gamma played an important role here, while most other countries reported a new infection caused by the Delta variant. The genetic and epidemiological information of this study reinforces the relevance of having a robust genomic surveillance service that allows better management of the pandemic and that provides efficient solutions to possible new disease-causing agents.

Physiotherapy Methods Applied in the Prevention of Functional Loss Associated with Human T-Lymphotropic Virus 1 Infection: An Overview.

To achieve the objective of this study, we conducted a narrative review on physical therapeutic modalities applied to prevent functional losses associated with human T-lymphotropic virus 1 (HTLV-1) infections to promote health education and viable and accessible alternatives in the development of health education technology adapted to the home environment. This study comprised a qualitative stage of theoretical development to construct a digital booklet with an observational basis based on studies that reiterate themes about educational technologies as tools to conduct a home protocol of guided exercises without the direct supervision of professional physical therapists. Results indicate a lack of research on the development of health education technologies to assist patients with HTLV-1 without tropical spastic paraparesis or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We believe that this narrative review can initiate a theoretical framework to conduct a home exercise program aimed at people with HTLV-1 who have subtle symptoms, and also at people without the clinical definition of HAM/TSP, helping to train human resources for care and research on the subject and increase scientific production in physical therapy.

The FOXP3-924 A/G Single Nucleotide Polymorphism May Be Associated with Predictive Factors for Human T Lymphotropic Virus 1 Associated Myelopathy.

Human T lymphotropic virus 1 (HTLV-1) is a retrovirus associated with inflammatory diseases, including HTLV-1-associated myelopathy (HAM), and host genetic factors may be involved in disease evolution. The forkhead Box P3 (FOXP3) transcription factor is linked to homeostasis of the immune system, and the presence of polymorphisms in the promoter region of the FOXP3 gene should reflect its expression levels and consequent activation of regulatory T cells, which may contribute to severe inflammatory disorders, such as HAM. This study evaluated the rs2232365 polymorphism (-924 A/G) located in the promoter region of the FOXP3 gene and its association with HAM. Forty DNA samples from asymptomatic carriers and 25 samples from HAM patients were used, in addition to 130 control samples. The polymorphism was genotyped by conducting real-time polymerase chain reaction (PCR) (quantitative PCR [qPCR]) on extracted DNA. The proviral loads (PVLs) and CD4+ and CD8+ T lymphocyte counts were determined by qPCR and FACSCalibur flow cytometry, respectively. The PVLs, CD4+ T lymphocyte concentrations, and tumor necrosis factor-α dosages were considered predictive factors of the clinical profiles of HTLV-1 infection, all of which had higher levels in the HAM group. Carriers of the GG genotype for the polymorphism rs2232365 had high PVLs and CD4+ T lymphocyte concentrations.

Antiulcerogenic and healing activity of hecogenin acetate in rodents.

Peptic ulcers are lesions in the gastric and duodenal mucosa generated by an imbalance between protective factors (gastroduodenal mucus secretion, bicarbonate production, adequate blood flow) and harmful factors (excess pepsin or hydrochloric acid). Some drugs used in peptic ulcer therapy are associated with adverse effects. The aim of this study was to evaluate the antiulcerogenic and healing activity of hecogenin acetate (HA) in acute and chronic models of gastric lesions in rodents. The antiulcerogenic activity of HA was evaluated in models of gastric lesions induced by absolute ethanol and in acidified ethanol with HA (5, 10, and 20 mg/kg). For the model of gastric lesions induced by ischemia and reperfusion, rats were pre-treated with HA (5, 10, 20 mg/kg). After that, they were submitted to 30 min of ischemia, followed by 1 h of reperfusion. To evaluate the healing activity was induced gastric ulcer using acetic acid (80%) in rats. After 24 h, they were treated for 7 consecutive days with HA (10 and 20 mg/kg). They were evaluated the possible signs of toxicity, measurement of the lesions, collagen deposition, and histological analysis. HA significantly reduced the area of the lesion in models of gastric lesions induced by absolute and acidified ethanol, ischemia-induced gastric lesions and reperfusion, and regarding healing. In the collagen deposition, the presence and increase of collagen demonstrate the healing effect. The AH has antiulcerogenic and healing potential demonstrated by the decrease in gastric injury and presence of collagen fibers, respectively.

Hematological changes in human lymphotropic-T virus type 1 carriers.

The human T-lymphotropic virus type 1 (HTLV-1), isolated in 1980, causes T-cell leukemia/lymphoma in adulthood, a type of lymphoproliferative disease, and chronic HTLV-1-associated myelopathy, a disease that causes paralysis of the lower limbs, which occur in about 5% of cases in this viral infection. This study aimed to establish the hematological profile of patients with HTLV-1 infection in Belém do Pará, describing the hematological parameters under study, estimating the frequency of lymphocytic atypical, and associating the hematological profile with diseases and symptoms. Hematologic data from 202 individuals were analyzed, including 87 HTLV-1 infected individuals and 115 non-HTLV-1 infected individuals as a control group, composed, at a great part, of relatives of the infected. The seroprevalence of HTLV-1 infection was observed in 71.3% of female individuals, with predominance in the group older than 50 years (44.8%). The analysis of hematological parameters showed a significant difference in the counts of the segmented cells (p = 0.0303) and eosinophils (p = 0.0092) in HTLV-1 carriers. Lymphocytic atypical was a finding present only in HTLV-1 carriers (p = 0.0001). There was no high frequency in the leukocyte counts of those infected by HTLV-1 not among them concerning a significant increase or decrease. It is concluded that HTLV-1 infection is prominent in women over 50 years old. The hematological profile of those infected shows a reduction of segmented cells, an increase of eosinophils, and the presence of atypical lymphocytes. The hematological profile of the HTLV-1 carrier should always be evaluated to identify early some diseases associated with the infection.

High prevalence of sexual infection by human papillomavirus and Chlamydia trachomatis in sexually-active women from a large city in the Amazon region of Brazil.

BACKGROUND: The Human Papillomavirus (HPV) and Chlamydia trachomatis are the most prevalent Sexually Transmitted Infections (STIs) worldwide, and are associated cervical cancer and pelvic inflammatory disease, respectively. However, 80% of women testing positive are asymptomatic. In the Amazon region, young women, in particular, are widely exposed to the infections and their consequences. OBJECTIVES: Determine the prevalence of sexual infection by HPV and C. trachomatis in young, sexually-active women treated at a university health program in a large city of the Brazilian Amazon region. METHODS: We amplified the L1 gene of HPV. We amplified ompA gene of C. trachomatis by nested PCR, and the study participants filled in a questionnaire on their social, epidemiological, and reproductive health characteristics. The data were analyzed using the Odds Ratio, to evaluate the degree of association of these variables with the observed infections. RESULTS: The prevalence of infection by HPV was 15.5% (47/303). This infection was recorded in 32.2% of the women of less than 25 years of age (OR:3.02 [CI95%] = 1.32-6.92; p = 0.014), 17.9% of the single women (OR: 2.41 [CI95%] = 1.22-4.75; p = 0.014), 23.8% of the women that reported having first sexual intercourse at less than 15 years of age (OR: 2.22 [CI95%] = 1.16-4.23; p = 0.021), 20% of those that reported having had more than one sexual partner during their lifetime (OR: 3.83 [CI95%] = 1.56-9.37; p = 0.003), and in 28.3% that use oral contraceptives (CI95% = 1.33-5.43; p = 0.008). The prevalence of sexual infection by C. trachomatis was 4.6% (14/303), and this bacterium was present in 16.1% of the young women of less than 25 years of age (OR: 2.86 [CI95%] = 1.33-5.43; p = 0.008). CONCLUSIONS: We found a high prevalence of HPV in young, unmarried women who started their sex lives early, who had several sexual partners in their lives and who used oral contraceptives. The prevalence of C. trachomatis was high only in young women. Our data are in accordance with other studies in Brazil and in the world and may serve to base the formulation of diagnostic and screening measures for these infections in women in the Amazon.

Association of the p75NTR Ser205Leu Polymorphism with Asymptomatic HTLV-1 Infection.

Genetic variations in components of the immune response seem to be an important factor that contributes to the manifestation of symptoms of some diseases related to HTLV-1 infection. Nerve growth factor (NGF) and the p75 neurotrophin receptor (p75NTR) are related to the maintenance of neurons and the activation of the immune response. In this study, we evaluated the association of the NGF -198C/T, NGF Ala35Val, and p75NTR Ser205Leu polymorphisms with HTLV-1 infection and plasma cytokine levels in 166 samples from individuals infected with HTLV-1 (59 symptomatic and 107 asymptomatic). The genotyping and quantification of the proviral load were performed by real-time PCR, and cytokine levels were measured by ELISA. The NGF -198C/T and NGF Ala35Val polymorphisms were not associated with HTLV-1 infection. The frequency of the Ser/Leu genotype of p75NTR Ser205Leu was more frequent in the control group (p = 0.0385), and the Ser/Leu genotype and allele Leu were more frequent among the asymptomatic (p < 0.05), especially with respect to the HTLV-1-associated myelopathy (HAM) group (p < 0.05). The symptomatic showed a higher proviral load and higher TNF-α and IL-10 levels (p < 0.05). Asymptomatic carriers of the Ser/Leu genotype (p = 0.0797) had lower levels of proviral load and higher levels of TNF-α (p = 0.0507). Based on the results obtained, we conclude that the p75NTR Ser205Leu polymorphism may be associated with reduced susceptibility to HTLV-1 infection, a lower risk of developing symptoms, including HAM, and better infection control.

Rapid and Sensitive Qualitative Duoplex Real-Time PCR Method for Discriminatory and Confirmatory Diagnosis of HTLV-1 and HTLV-2 Infections: Brazilian Multicentric Study.

Human T cell lymphotropic virus (HTLV) is the caustive agent of two main conditions i. e., the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and the adult T-cell leukemia/lymphoma (ATLL). HTLV diagnosis is based on serological and molecular approaches; however, an accurate and validated method is still needed. The objective of this study was to establish a rapid and sensitive molecular test to confirm and discriminate HTLV 1/2 types. The test validation was performed as a multicentric study involving HTLV confirmation centers throughout Brazil. Proviral DNA was extracted from whole blood and the amplification was performed using in-house designed primer and probe sets targeting the pol genomic region. An internal control to validate the extraction and amplification was also included. The limit of detection (LoD) of the assay was four copies/reaction for HTLV-1 and 10.9 copies/reaction for HTLV-2. The diagnostic sensitivity of the platform was 94.6% for HTLV-1, 78.6% for HTLV-2, and the specificity was 100% for both viruses. Cross-reactions of the test with human viruses including HAV, HBV, HCV, HIV-1/2, and parvovirus B19 were not observed. During the multicentric validation, the test was used to screen a total of 692 blood samples obtained from previously confirmed HTLV-positive individuals. From these, 91.1% tested positive being concordant with the previously obtained results. In conclusion, our duoplex-RT-PCR-HTLV1 /2 presented adequate efficiency for HTLV-1/2 differentiation showing high sensitivity and specificity. Therefore, it can be a suitable tool for confirmation of suspected and inconclusive HTLV cases, prenatal and pre-transplant diagnosis, in Brazil and in other countries HTLV-endemic countries.

Desenvolvimento de webtecnologia educacional sobre citologia clínica para estudantes e profissionais da área da saúde / Desarrollo de tecnología web educativa. sobre citología clínica para estudiantes y profesionales de la salud / Development of educational webtechnology on clinical cytology for students and healthcare professionals

Objetivo: Descrever o processo de desenvolvimento de uma webtecnologia educacional, do tipo blog, sobre citologia clínica, para estudantes e profissionais da área da saúde. Métodos: Pesquisa metodológica para construção de tecnologia educacional em saúde, desenvolvida em três etapas: Revisão da literatura (2019), a partir da qual se deu o delineamento teórico; Fotodocumentação (2020), que foi a fase responsável pela obtenção do conteúdo imagético; Construção (2020-2021), a partir da qual se deu a criação do blog. Resultados: Na primeira fase, obteve-se a fundamentação teórica. Na segunda fase, realizou-se a obtenção das imagens e na terceira fase, o desenvolvimento do produto técnico-tecnológico. Conclusão: O blog, emerge como modelo de suporte para proporcionar um caráter de ubiquidade à informação e como consequência disso, ampliar o potencial gerador de conhecimento sobre citologia clínica entre estudantes e profissionais de diversos campos da área da saúde, com enfoque à Biomedicina e Enfermagem(AU)

Objective: To describe the development process of an educational webtechnology, like a blog, about clinical cytology, for students and health professionals. Methods: Methodological research for the construction of educational technology in health, developed in three stages: Literature review (2019), from which the theoretical outline was given; Photodocumentation (2020), which was the phase responsible for obtaining the image content; Construction (2020-2021), from which the creation of the blog took place. Results: In the first phase, the theoretical foundation was obtained. In the second phase, the images were obtained and in the third phase, the development of the technical-technological product. Conclusion: The blog emerges as a support model to provide a ubiquitous character to information and, as a consequence, expand the potential generator of knowledge about clinical cytology among students and professionals from different fields of health, with a focus on Biomedicine and Nursing(AU)

Objetivo: Describir el proceso de desarrollo de una tecnología web educativa, como un blog, sobre citología clínica, para estudiantes y profesionales de la salud. Métodos: Investigación metodológica para la construcción de tecnología educativa en salud, desarrollada en tres etapas: Revisión de la literatura (2019), a partir de la cual se dio el esquema teórico; Fotodocumentación (2020), que fue la fase encargada de obtener el contenido de la imagen; Construcción (2020-2021), a partir de la cual tuvo lugar la creación del blog. Resultados: En la primera fase se obtuvo el fundamento teórico. En la segunda fase se obtuvieron las imágenes y en la tercera fase, el desarrollo del producto técnico-tecnológico. Conclusión: El blog surge como un modelo de apoyo para dotar de un carácter ubicuo a la información y, como consecuencia, ampliar el potencial generador de conocimiento sobre citología clínica entre estudiantes y profesionales de diferentes campos de la salud, con enfoque en Biomedicina y Enfermería(AU)

Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients. METHODS: This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group (p = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals (p = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000). CONCLUSIONS: Our results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.

Sex and FOXP3 gene rs2232365 polymorphism may be associated with the clinical and pathological aspects of chronic viral diseases.

BACKGROUND: The forkhead box protein 3 (FOXP3) transcription factor is one of the main markers of immunological suppression in different pathological profiles, and the presence of polymorphic variants may alter the gene expression of this factor. Despite descriptions of an association between the presence of the rs2232365 polymorphism and chronic diseases, the role of the sex variant in this context has not yet been elucidated, as the FOXP3 gene is located on the human sex chromosome X. RESULTS: To contribute to this topic, 323 women and 373 men were enrolled in the study, of which 101 were diagnosed with chronic viral liver diseases (39 women and 62 men), 67 with HTLV-1 infection (44 women and 23 men), 230 with coronary artery disease (91 women and 139 men) and 298 healthy and uninfected blood donors (149 women and men). They were genotyped for the rs2232365 polymorphism. The rs2232365 polymorphism was associated with clinical and pathological aspects and biomarkers of viral infections only in men, with functional differences between different infections. CONCLUSIONS: A relationship is suggested between sex and FOXP3 rs2232365 polymorphism, resulting in different biological repercussions.

The SAMHD1 rs6029941 (A/G) Polymorphism Seems to Influence the HTLV-1 Proviral Load and IFN-Alpha Levels.

SAMHD1, a host dNTPase, acts as a retroviral restriction factor by degrading the pool of nucleotides available for the initial reverse transcription of retroviruses, including HTLV-1. Polymorphisms in the SAMDH1 gene may alter the enzymatic expression and influence the course of infection by the virus. The present study investigated the effect of polymorphisms on HTLV-1 infection susceptibility and on progression to disease in 108 individuals infected by HTLV-1 (47 symptomatic and 61 asymptomatic) and 100 individuals in a control group. SAMHD1 rs6029941 (G/A) genotyping and HTLV-1 proviral load measurements were performed using real-time PCR and plasma IFN-α was measured by ELISA. Polymorphism frequency was not associated with HTLV-1 infection susceptibility or with the presence of symptoms. The proviral load was significantly higher in symptomatic individuals with the G allele (p = 0.0143), which presented lower levels of IFN-α (p = 0.0383). SAMHD1 polymorphism is associated with increased proviral load and reduced levels of IFN-α in symptomatic patients, and may be a factor that contributes to the appearance of disease symptoms.

As descobertas genômicas do SARS-CoV-2 e suas implicações na pandemia de COVID-19 / The genomic discoveries of SARS-CoV-2 and their implications for the COVID-19 pandemic

Objetivo: Auxiliar no entendimento da COVID-19 em relação à origem do SARS-CoV-2, suas descobertas genômicas, patogenia, possíveis hospedeiros primários e intermediários, além da comparação com outros coronavírus. Metodos: foram utilizadas as bases de dados Scientific Eletronic Library Online e PubMed, com artigos de revisão e originais, em língua portuguesa e inglesa, pesquisados no período de 05 de março a 10 de abril de 2020, adotando os seguintes descritores: SARS-CoV, COVID-19, coronavirus, Wuhan, genome, structure, origin, transmission, evolution, zoonotic. Os artigos originais identificados foram incluídos nesta revisão, juntamente com artigos de suporte referenciados por estes. Resultados: As características genômicas descritas até o momento podem explicar, em parte, a infectividade e a transmissibilidade do SARS-CoV-2 em humanos. Devido aos notáveis recursos de SARS-CoV-2, incluindo o local otimizado do domínio de ligação ao receptor (RBD) e de clivagem polibásica, é pouco provável um cenário laboratorial para a origem do SARS-CoV-2. Conclusão: Para o presente, é de extrema importância obter mais dados genéticos e funcionais sobre o SARS-CoV-2, incluindo estudos em animais, sequenciamento do vírus em casos muito precoces e identificação dos parentes virais mais próximos do SARS-CoV-2 que circulam em animais.(AU)

Objective: To assist in the understanding of COVID-19 in relation to the origin of SARS-CoV-2, its genomic discoveries, pathogenesis, possible primary and intermediate hosts, in addition to comparison with other coronaviruses. Methods: the Scientific Electronic Library Online and PubMed databases were used, with review articles and originals, in Portuguese and English, researched from March 5 to April 10, 2020, adopting the following descriptors: SARS-CoV , COVID-19, coronavirus, Wuhan, genome, structure, origin, transmission, evolution, zoonotic. The original articles identified were included in this review, along with supporting articles referenced by them. Results: The genomic characteristics described so far may partly explain the infectivity and transmissibility of SARS-CoV-2 in humans. Due to the remarkable resources of SARS-CoV-2, including the optimized site of the receptor binding domain (RBD) and polybasic cleavage, a laboratory scenario for the origin of SARS-CoV-2 is unlikely. Conclusion: For the present, it is extremely important to obtain more genetic and functional data on SARS-CoV-2, including studies on animals, sequencing of the virus in very early cases and identification of the closest viral relatives of SARS-CoV-2 that circulate in animals.(AU)

TREX1 531C>T Polymorphism is Associated with High Proviral Load Levels in HTLV-1-Infected Persons.

Human T-lymphotropic virus type 1 (HTLV-1) deregulates the immune system and cell cycle, resulting in loss of immune tolerance and disease, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Three prime repair exonuclease 1 (TREX1) maintains innate immune tolerance of the host and host-cell permissiveness to retroviral infections. TREX1 polymorphisms may influence the course of infection and autoimmune manifestations. The influence of TREX1 531C/T polymorphism was investigated in HTLV-1 infection and development of symptoms among 151 persons infected with HTLV-1 (32 HAM/TSP, 19 rheumatologic manifestations, two dermatitis, five more than one diagnosis, two probable HAM/TSP, and 91 asymptomatic individuals) and 100 uninfected persons in the control group. Polymorphism genotyping and proviral load quantification were performed by real-time polymerase chain reaction (PCR) and antinuclear antibodies (ANAs) were screened by an indirect immunofluorescence assay. No statistically significant difference was found in polymorphism genotype and allele frequencies between the infected and control groups. HAM/TSP patients showed higher frequency of TT genotype than asymptomatic persons (p = 0.0339). Proviral load was significantly higher among individuals with CT/TT genotypes and CC genotype carriers had lower proviral load and higher levels of proinflammatory cytokines. ANAs were present only in the HAM/TSP group. TREX1 531C>T polymorphism seems to be associated with TREX-1 regulation and HTLV-1 infection.