Genomic Detection of the Emerging, Highly Pathogenic HIV-1 Subtype D in Bahia, Northeast Brazil.

(1) Background: The HIV subtype D is generally associated with a faster decline in CD4+ T cell counts, a higher viral load, and a faster progression to AIDS. However, it is still poorly characterized in Brazil. In this study, we used genomics and epidemiological data to investigate the transmission dynamics of HIV subtype D in the state of Bahia, Northeast Brazil. (2) Methods: To achieve this goal, we obtained four novel HIV-1 subtype D partial pol genome sequences using the Sanger method. To understand the emergence of this novel subtype in the state of Bahia, we used phylodynamic analysis on a dataset comprising 3704 pol genome sequences downloaded from the Los Alamos database. (3) Results: Our analysis revealed three branching patterns, indicating multiple introductions of the HIV-1 subtype D in Brazil from the late 1980s to the late 2000s and a single introduction event in the state of Bahia. Our data further suggest that these introductions most likely originated from European, Eastern African, Western African, and Southern African countries. (4) Conclusion: Understanding the distribution of HIV-1 viral strains and their temporal dynamics is crucial for monitoring the real-time evolution of circulating subtypes and recombinant forms, as well as for designing novel diagnostic and vaccination strategies. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics mediated by emerging viral strains.

An overview of sequencing technology platforms applied to HTLV-1 studies: a systematic review.

Human T-lymphotropic virus type 1 (HTLV-1) was the first human retrovirus described. The viral factors involved in the different clinical manifestations of infected individuals are still unknown, and in this sense, sequencing technologies can support viral genome studies, contributing to a better understanding of infection outcome. Currently, several sequencing technologies are available with different approaches. To understand the methodological advances in the HTLV-1 field, it is necessary to organize a synthesis by a rigorous review. This systematic literature review describes different technologies used to generate HTLV-1 sequences. The review follows the PRISMA guidelines, and the search for articles was performed in PubMed, Lilacs, Embase, and SciELO databases. From the 574 articles found in search, 62 were selected. The articles showed that, even with the emergence of new sequencing technologies, the traditional Sanger method continues to be the most commonly used methodology for generating HTLV-1 genome sequences. There are many questions that remain unanswered in the field of HTLV-1 research, and this reflects on the small number of studies using next-generation sequencing technologies, which could help address these gaps. The data compiled and analyzed here can help research on HTLV-1, assisting in the choice of sequencing technologies.

Molecular characterization of HTLV-1 genomic region hbz from patients with different clinical conditions.

The human T-cell lymphotropic virus type-1 (HTLV-1) is associated with severe pathologies, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), adult T-cell leukemia-lymphoma (ATLL), and infective dermatitis associated with the HTLV-1 (IDH). Interestingly, HTLV-1 infection does not necessarily imply the development of pathological processes and it is unknown why some patients remain asymptomatic carriers (AC). Despite some mutations in the HTLV-1 genome appear to influence the outcome of HTLV-1, there are few studies that characterize molecularly the hbz region. This study aimed to perform the molecular characterization of hbz gene isolated from patients with different clinical outcomes. A total of 15 sequences were generated and analyzed with 571 sequences previously published. The analises showed that the R119Q mutation seems to be related to HTLV-1 clinical conditions since the frequency of this HBZ mutation is significantly different in comparison between AC with HAM/TSP and ATLL. The R119Q mutation is possibly a protective factor as the frequency is higher in AC sequences.

Molecular Epidemiology Database for Sequence Management and Data Mining.

A central database to aggregate sequence information from a range of epidemiological aspects including HTLV-1 pathogenesis, origin, and evolutionary dynamic would be useful to scientists and physicians worldwide. This Chapter describes two online tools for studies related to HTLV-1, the HTLV-1 Molecular Epidemiology Database and the HTLV-1 Subtyping Tool. The HTLV-1 Molecular Epidemiology Database is a tool for sequence management and data mining which allows researchers to download sequences with clinical and demographic information. The HTLV-1 Subtyping Tool is an online software used for HTLV-1 genotyping, the algorithm consists in the alignment of a query sequence with a carefully selected set of predefined reference strains, followed by phylogenetic analysis.

HTLV-1aA introduction into Brazil and its association with the trans-Atlantic slave trade.

INTRODUCTION: Human T-lymphotropic virus (HTLV) is an endemic virus in some parts of the world, with Africa being home to most of the viral genetic diversity. In Brazil, HTLV-1 is endemic amongst Japanese and African immigrant populations. Multiple introductions of the virus in Brazil from other epidemic foci were hypothesized. The long terminal repeat (LTR) region of HTLV-1 was used to infer the origin of the virus in Brazil, using phylogenetic analysis. METHODS: LTR sequences were obtained from the HTLV-1 database (http://htlv1db.bahia.fiocruz.br). Sequences were aligned and maximum-likelihood and Bayesian tree topologies were inferred. Brazilian specific clusters were identified and molecular-clock and coalescent models were used to estimate each cluster's time to the most recent common ancestor (tMRCA). RESULTS: Three Brazilian clusters were identified with a posterior probability ranged from 0.61 to 0.99. Molecular clock analysis of these three clusters dated back their respective tMRCAs between the year 1499 and the year 1668. Additional analysis also identified a close association between Brazilian sequences and new sequences from South Africa. CONCLUSION: Our results support the hypothesis of a multiple introductions of HTLV-1 into Brazil, with the majority of introductions occurring in the post-Colombian period. Our results further suggest that HTLV-1 introduction into Brazil was facilitated by the trans-Atlantic slave trade from endemic areas of Africa. The close association between southern African and Brazilian sequences also suggested that greater numbers of the southern African Bantu population might also have been part of the slave trade than previously thought.

Oral health profile in patients infected with HTLV-1: clinical findings, proviral load, and molecular analysis from HTLV-1 in saliva.

Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and has also been implicated in several disorders, including periodontal disease. The proviral load is an important biological marker for understanding HTLV-1 pathogenesis and elucidating whether or not the virus is related to the clinical manifestation of the disease. This study describes the oral health profile of HTLV-1 carriers and HAM/TSP patients in order to investigate the association between the proviral load in saliva and the severity of the periodontal disease and to examine virus intra-host variations from peripheral blood mononuclear cells and saliva cells. It is a cross-sectional analytical study of 90 individuals carried out from November 2006 to May 2008. Of the patients, 60 were HTLV-1 positive and 30 were negative. Individuals from the HTLV-1 positive and negative groups had similar mean age and social-economic status. Data were analyzed using two available statistical software packages, STATA 8.0 and SPSS 11.0 to conduct frequency analysis. Differences of P < 0.05 were considered statistically significant. HTLV-1 patients had poorer oral health status when compared to seronegative individuals. A weak positive correlation between blood and saliva proviral loads was observed. The mean values of proviral load in blood and saliva in patients with HAM/TSP was greater than those in HTLV-1 carriers. The HTLV-1 molecular analysis from PBMC and saliva specimens suggests that HTLV-1 in saliva is due to lymphocyte infiltration from peripheral blood. A direct relationship between the proviral load in saliva and oral manifestations was observed.

Seroprevalence and molecular epidemiology of HTLV-1 isolates from HIV-1 co-infected women in Feira de Santana, Bahia, Brazil.

HTLV-1/HIV-1 co-infection is associated with severe clinical manifestations, marked immunodeficiency, and opportunistic pathogenic infections, as well as risk behavior. Salvador, the capital of the State of Bahia, Brazil, has the highest HTLV-1 prevalence (1.74%) found in Brazil. Few studies exist which describe this co-infection found in Salvador and its surrounding areas, much less investigate how these viruses circulate or assess the relationship between them. To describe the epidemiological and molecular features of HTLV in HIV co-infected women. To investigate the prevalence of HTLV/HIV co-infection in surrounding areas, as well as the molecular epidemiology of HTLV, a cross sectional study was carried out involving 107 women infected with HIV-1 from the STD/HIV/AIDS Reference Center located in the neighboring City of Feira de Santana. Patient samples were submitted to ELISA, and HTLV infection was confirmed using Western Blot and Polymerase Chain Reaction (PCR). Phylogenetic analysis using Neighbor-Joining (NJ) and Maximum Likelihood (ML) was performed on HTLV LTR sequences in order to gain further insights about molecular epidemiology and the origins of this virus in Bahia. Four out of five reactive samples were confirmed to be infected with HTLV-1, and one with HTLV-2. The seroprevalence of HTLV among HIV-1 co-infected women was 4.7%. Phylogenetic analysis of the LTR region from four HTLV-1 sequences showed that all isolates were clustered into the main Latin American group within the Transcontinental subgroup of the Cosmopolitan subtype. The HTLV-2 sequence was classified as the HTLV-2c subtype. It was also observed that four HTLV/HIV-1 co-infected women exhibited risk behavior with two having parenteral exposure, while another two were sex workers. This article describes the characteristics of co-infected patients. This co-infection is known to be severe and further studies should be conducted to confirm the suggestion that HTLV-1 is spreading from Salvador to surrounding areas.