RESUMO
The spread of Chikungunya virus is a major public health concern in the Americas. There were >120,000 cases and 51 deaths in 2023, of which 46 occurred in Paraguay. Using a suite of genomic, phylodynamic, and epidemiologic techniques, we characterized the ongoing large chikungunya epidemic in Paraguay.
Assuntos
Febre de Chikungunya , Vírus Chikungunya , Epidemias , Humanos , Vírus Chikungunya/genética , Paraguai/epidemiologia , África do Sul , Febre de Chikungunya/epidemiologia , Filogenia , GenótipoRESUMO
São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species.
Assuntos
Genoma Viral , Doenças dos Primatas/virologia , Febre Amarela/veterinária , Febre Amarela/virologia , Vírus da Febre Amarela/genética , Zoonoses/virologia , Animais , Brasil/epidemiologia , Surtos de Doenças , Genômica , Humanos , Filogenia , Filogeografia , Doenças dos Primatas/epidemiologia , Doenças dos Primatas/transmissão , Primatas/virologia , Febre Amarela/epidemiologia , Febre Amarela/transmissão , Vírus da Febre Amarela/classificação , Vírus da Febre Amarela/isolamento & purificação , Zoonoses/epidemiologia , Zoonoses/transmissãoRESUMO
The Lambda variants of interest (VOI) (C37/GR/452Q.V1/21G) was initially reported in Lima, Peru but has gained rapid dissemination through other Latin American countries. Nevertheless, the dissemination and molecular epidemiology of the Lambda VOI in Brazil is unknown apart from a single case report. In this respect, we characterized the circulation of the SARS-CoV-2 Lambda VOI (C37/GR/452Q.V1/21G) in Sao Paulo State, Brazil. From March to June 2021, we identified seven Lambda isolates in a set of approximately 8000 newly sequenced genomes of the Network for Pandemic Alert of Emerging SARS-CoV-2 variants from Sao Paulo State. Interestingly, in three of the positive patients, the Lambda VOI infection was probably related to a contact transmission. These individuals were fully vaccinated to COVID-19 and presented mild symptoms. The remaining positive for Lambda VOI individuals showed different levels of COVID-19 symptoms and one of them needed hospitalization (score 5, WHO). In our study, we present a low level of Lambda VOI circulation in the Sao Paulo State. This reinforces the essential role of molecular surveillance for the effective SARS-CoV-2 pandemic response, especially in regard to circulating variants.
Assuntos
COVID-19 , SARS-CoV-2 , Brasil/epidemiologia , COVID-19/epidemiologia , Humanos , SARS-CoV-2/genética , Organização Mundial da SaúdeRESUMO
BACKGROUND: Cross-reactivity to SARS-CoV-2 from exposure to endemic human coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and COVID-19 severity. Here we explore the potential role of cross-reactivity induced by eHCoVs on age-specific COVID-19 severity in a mathematical model of eHCoV and SARS-CoV-2 transmission. METHODS: We use an individual-based model, calibrated to prior knowledge of eHCoV dynamics, to fully track individual histories of exposure to eHCoVs. We also model the emergent dynamics of SARS-CoV-2 and the risk of hospitalisation upon infection. RESULTS: We hypothesise that primary exposure with any eHCoV confers temporary cross-protection against severe SARS-CoV-2 infection, while life-long re-exposure to the same eHCoV diminishes cross-protection, and increases the potential for disease severity. We show numerically that our proposed mechanism can explain age patterns of COVID-19 hospitalisation in EU/EEA countries and the UK. We further show that some of the observed variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates under this model. CONCLUSIONS: This study provides a "proof of possibility" for certain biological and epidemiological mechanisms that could potentially drive COVID-19-related variation across age groups. Our findings call for further research on the role of cross-reactivity to eHCoVs and highlight data interpretation challenges arising from health care capacity and SARS-CoV-2 testing.
Assuntos
COVID-19 , Infecções por Coronavirus , Proteção Cruzada/imunologia , Reações Cruzadas/imunologia , SARS-CoV-2/imunologia , Fatores Etários , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/fisiopatologia , Coronavirus/classificação , Coronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Doenças Endêmicas , Hospitalização/estatística & dados numéricos , Humanos , Imunidade Heteróloga/imunologia , Modelagem Computacional Específica para o Paciente , Índice de Gravidade de DoençaRESUMO
This study tested the hypothesis that sickle red blood cell (SS-RBC) induce Toll-like receptors (TLR) and Nod-like receptor family, pyrin domain containing 3 (NLRP3)- inflammasome expression in peripheral blood mononuclear cells (PBMC). TLR and NLRP3 inflammasome could contribute to the maintenance of the inflammatory status in sickle cell anemia (SCA) patients, since SS-RBC act as danger signals activating these pathways. In this study, first, we evaluated TLR (2, 4, 5 and 9), NLRP3, Caspase-1, interleukin (IL)-1ß and IL-18 expression in PBMC freshly isolated from SCA patients (SS-PBMC) in comparison with PBMC from healthy individuals (AA-PBMC). In the second moment, we investigated whether SS-RBC could interfere with the expression of these molecules in PBMC from healthy donor, in the absence or presence of hydroxyurea (HU) in vitro. TLRs and NLRP3 inflammasome expression were investigated by qPCR. IL-1ß, Leukotriene-B4 (LTB4) and nitrite production were measured in PBMC (from healthy donor) culture supernatants. TLR2, TLR4, TLR5, NLRP3 and IL-1ß were highly expressed in SS-PBMC when compared to AA-PBMC. Additionally, SS-RBC induced TLR9, NLRP3, Caspase-1, IL-1ß and IL-18 expression and induced IL-1ß, LTB4 and nitrite production in PBMC cultures. HU did not prevent TLR and NLRP3 inflammasome expression, but increased TLR2 and IL-18 expression and reduced nitrite production. In conclusion, our data suggest that TLR and inflammasome complexes may be key inducers of inflammation in SCA patients, probably through SS-RBC; also, HU does not prevent NLRP3 inflammasome- and TLR-dependent inflammation, indicating the need to develop new therapeutic strategies to SCA patients that act with different mechanisms of those observed for HU.
Assuntos
Anemia Falciforme/metabolismo , Eritrócitos Anormais/metabolismo , Regulação da Expressão Gênica , Interleucina-1beta/biossíntese , Leucócitos Mononucleares/metabolismo , Leucotrieno B4/biossíntese , Adolescente , Anemia Falciforme/patologia , Criança , Pré-Escolar , Eritrócitos Anormais/patologia , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Interleucina-18/biossíntese , Leucócitos Mononucleares/patologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/biossíntese , Nitritos/metabolismo , Receptores Toll-Like/biossínteseRESUMO
SUMMARY: RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyse patient data, including viral genetic sequences. Moreover, RegaDB provides researchers with a mechanism to collect data in a uniform format and offers them a canvas to make newly developed bioinformatics tools available to clinicians and virologists through a user friendly interface. AVAILABILITY AND IMPLEMENTATION: Source code, binaries and documentation are available on http://rega.kuleuven.be/cev/regadb. RegaDB is written in the Java programming language, using a web-service-oriented architecture.
Assuntos
Bases de Dados Factuais , Software , Viroses , Sistemas de Gerenciamento de Base de Dados , Humanos , Viroses/diagnóstico , Viroses/terapia , Viroses/virologiaRESUMO
In 2015, the Zika virus (ZIKV) emerged in Brazil, leading to widespread outbreaks in Latin America. Following this, many countries in these regions reported a significant drop in the circulation of dengue virus (DENV), which resurged in 2018-2019. We examine age-specific incidence data to investigate changes in DENV epidemiology before and after the emergence of ZIKV. We observe that incidence of DENV was concentrated in younger individuals during resurgence compared to 2013-2015. This trend was more pronounced in Brazilian states that had experienced larger ZIKV outbreaks. Using a mathematical model, we show that ZIKV-induced cross-protection alone, often invoked to explain DENV decline across Latin America, cannot explain the observed age-shift without also assuming some form of disease enhancement. Our results suggest that a sudden accumulation of population-level immunity to ZIKV could suppress DENV and reduce the mean age of DENV incidence via both protective and disease-enhancing interactions.
Assuntos
Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Humanos , Brasil/epidemiologia , Anticorpos Antivirais , Reações CruzadasRESUMO
Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system. Here we propose adding two sub-genotypic levels of virus classification, named major and minor lineages. These lineages have high thresholds for phylogenetic distance and clade size, rendering them stable between phylogenetic studies. We present an assignment tool to show that the proposed lineages are useful for regional, national and sub-national discussions of relevant DENV diversity. Moreover, the proposed lineages are robust to classification using partial genome sequences. We provide a standardized neutral descriptor of DENV diversity with which we can identify and track lineages of potential epidemiological and/or clinical importance. Information about our lineage system, including methods to assign lineages to sequence data and propose new lineages, can be found at: dengue-lineages.org.
RESUMO
BACKGROUND: Human T-cell Leukemia Virus type 1 (HTLV-1) is the etiological agent of tropical spastic paraparesis/HTLV-associated myelopathy (HAM/TSP) that can be identified in around 0.25%-3.8% of the infected population. Disease progression can be monitored by the proviral load and may depend on genetic factors, however, it is not well understood why some HTLV-1 infected people develop the disease while others do not. The present study attempts to assess the molecular diversity of gp46 glycoprotein in HAM/TSP patients and Health Carrier (HC) individuals. METHODS: Blood samples were collected from 10 individuals, and DNA was extracted from PBMCs to measure the HTLV-1 proviral load. The gp46 coding sequences were amplified PCR, cloned and sequenced. The molecular characterization was performed using bioinformatics tools. RESULTS: The median HTLV-1 proviral load of HC (n = 5) and HAM/TSP (n = 5) patients was similar (average 316,227 copies/106 PBMCs). The gp46 molecular characterization of 146 clones (70 HC and 76 HAM/TSP) revealed an overall diversity, within HC and HAM/TSP clones, of 0.4% and 0.6%, respectively. Five frequent mutations were detected among groups (HAM/TSP and HC clone sequences). A single amino acid (aa) substitution (S35L) was exclusive for the HC group, and three gp46 substitutions (F14S, N42H, G72S) were exclusive for the HAM/TSP group. The remaining frequent mutation (V247I) was present in both groups (p = 0.0014). The in silico protein analysis revealed that the mutated alleles F14S and N42H represent more hydrophilic and flexible protein domains that are likely to be less antigenic. The Receptor Binding Domain is quite variable in the HAM/TSP group. Two other domains (aa 53-75 and 175-209) that contain multiple linear T-cell epitopes showed genetic diversity in both HAM/TSP and HC groups. Further analysis revealed 27 and 13 T-cell epitopes for class I HLA alleles and class II HLA alleles, when analyzing the entire gp46. CONCLUSIONS: The most common gp46 mutations were not associated clinical status because they were found in only one individual, except for the V247I mutation, that was found at viral clones from HAM/TSP ad HC individuals. Because of this, we cannot associate any of the gp46 found mutations with the clinical profile.
Assuntos
Portador Sadio/virologia , Produtos do Gene env/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/virologia , Proteínas Oncogênicas de Retroviridae/genética , Adulto , Idoso , Sequência de Aminoácidos , Portador Sadio/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Feminino , Produtos do Gene env/química , Produtos do Gene env/imunologia , Vírus Linfotrópico T Tipo 1 Humano/química , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Paraparesia Espástica Tropical/imunologia , Estrutura Terciária de Proteína , Proteínas Oncogênicas de Retroviridae/química , Proteínas Oncogênicas de Retroviridae/imunologiaRESUMO
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is responsible for causing Coronavirus Disease-2019 (COVID-19), a heterogeneous clinical condition that manifests varying symptom severity according to the demographic profile of the studied population. While many studies have focused on the spread of COVID-19 in large urban centers in Brazil, few have evaluated medium or small cities in the Northeast region. The aims of this study were: (i) to identify risk factors for mortality from SARS-CoV-2 infection, (ii) to evaluate the gene expression patterns of key immune response pathways using nasopharyngeal swabs of COVID-19 patients, and (iii) to identify the circulating SARS-CoV-2 variants in the residents of a medium-sized city in Northeast Brazil. A total of 783 patients infected with SARS-CoV-2 between May 2020 and August 2021 were included in this study. Clinical-epidemiological data from patients who died and those who survived were compared. Patients were also retrospectively divided into three groups based on disease severity: asymptomatic, mild, and moderate/severe. Samples were added to a qPCR array for analyses of 84 genes involved with immune response pathways and sequenced using the Oxford Nanopore MinION technology. Having pre-existing comorbidity; being male; having cardiovascular disease, diabetes, and/or chronic obstructive pulmonary disease; and PCR cycle threshold (Ct) values under 22 were identified as risk factors for mortality. Analysis of the expression profiles of inflammatory pathway genes showed that the greater the infection severity, the greater the activation of inflammatory pathways, triggering the cytokine storm and downregulating anti-inflammatory pathways. Viral genome analysis revealed the circulation of multiple lineages, such as B.1, B.1.1.28, Alpha, and Gamma, suggesting that multiple introduction events had occurred over time. This study's findings help identify the specific strains and increase our understanding of the true state of local health. In addition, our data demonstrate that epidemiological and genomic surveillance together can help formulate public health strategies to guide governmental actions.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Masculino , Feminino , SARS-CoV-2/genética , COVID-19/epidemiologia , Estudos Retrospectivos , Brasil/epidemiologiaRESUMO
Zika virus (ZIKV), an emerging virus belonging to the Flaviviridae family, causes severe neurological clinical complications and has been associated with Guillain-Barré syndrome, fetal abnormalities known collectively as congenital Zika syndrome, and microcephaly. Studies have shown that ZIKV infection can alter cellular metabolism, directly affecting neural development. Brain growth requires controlled cellular metabolism, which is essential for cell proliferation and maturation. However, little is known regarding the metabolic profile of ZIKV-infected newborns and possible associations related to microcephaly. Furthering the understanding surrounding underlying mechanisms is essential to developing personalized treatments for affected individuals. Thus, metabolomics, the study of the metabolites produced by or modified in an organism, constitutes a valuable approach in the study of complex diseases. Here, 26 serum samples from ZIKV-positive newborns with or without microcephaly, as well as controls, were analyzed using an untargeted metabolomics approach involving gas chromatography-mass spectrometry (GC-MS). Significant alterations in essential and non-essential amino acids, as well as carbohydrates (including aldohexoses, such as glucose or mannose) and their derivatives (urea and pyruvic acid), were observed in the metabolic profiles analyzed. Our results provide insight into relevant metabolic processes in patients with ZIKV and microcephaly.
RESUMO
Autochthonous Zika virus (ZIKV) transmission in Brazil was first identified in April 2015 in Brazil, with the first ZIKV-associated microcephaly cases detected in October 2015. Despite efforts on understanding ZIKV transmission in Brazil, little is known about the virus epidemiology and genetic diversity in Minas Gerais (MG), the second most populous state in the country. We report molecular and genomic findings from the main public health laboratory in MG. Until January 2020, 26,817 ZIKV suspected infections and 86 congenital syndrome cases were reported in MG state. We tested 8552 ZIKV and microcephaly suspected cases. Ten genomes were generated on-site directly from clinical samples. A total of 1723 confirmed cases were detected in Minas Gerais, with two main epidemic waves; the first and larger epidemic wave peaked in March 2016, with the second smaller wave that peaked in March 2017. Dated molecular clock analysis revealed that multiple introductions occurred in Minas Gerais between 2014 and 2015, suggesting that the virus was circulating unnoticed for at least 16 months before the first confirmed laboratory case that we retrospectively identified in December 2015. Our findings highlight the importance of continued genomic surveillance strategies combined with traditional epidemiology to assist public health laboratories in monitoring and understanding the diversity of circulating arboviruses, which might help attenuate the public health impact of infectious diseases.
Assuntos
Microcefalia/epidemiologia , Infecção por Zika virus/epidemiologia , Zika virus/genética , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Microcefalia/virologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem , Infecção por Zika virus/virologiaRESUMO
OBJECTIVE: To identify newborns with congenital Zika infection (CZI) at a maternity hospital in Salvador, Brazil, during the 2016 microcephaly outbreak. METHODS: A prospective study enrolled microcephalic and normocephalic newborns with suspected CZI between January and December 2016. Serology (immunoglobulins IgM and IgG) and quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) for the Zika virus were performed. Demographic and clinical characteristics of newborns with and without microcephaly were compared. RESULTS: Of the 151 newborns enrolled, 32 (21.2%) were classified as microcephalic. The majority of these cases were born between January and May 2016. IgM and IgG Zika virus antibodies were detected in 5 (23.8%) and 17 (80.9%) microcephalic newborn blood samples, respectively. Six (24%) microcephalic newborns tested positive for Zika virus by RT-qPCR in urine or placenta samples. Thirteen (11.8%) normocephalic newborns also tested positive for Zika virus by PCR in urine, plasma, or placenta samples, while IgM antibodies against Zika were detected in 4 (4.2%) others. CONCLUSIONS: Identification of 17 normocephalic CZI cases, confirmed by IgM serology or RT-qPCR for Zika virus, provides evidence that CZI can present asymptomatically at birth. This finding highlights the need for prenatal and neonatal screening for Zika virus in endemic regions.
Assuntos
Microcefalia/epidemiologia , Complicações Infecciosas na Gravidez/etiologia , Infecção por Zika virus/etiologia , Brasil/epidemiologia , Estudos de Casos e Controles , Surtos de Doenças , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Masculino , Microcefalia/sangue , Microcefalia/virologia , Triagem Neonatal/métodos , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Zika virus/isolamento & purificação , Infecção por Zika virus/sangue , Infecção por Zika virus/epidemiologiaRESUMO
In recent years, an increasing number of outbreaks of Dengue, Chikungunya and Zika viruses have been reported in Asia and the Americas. Monitoring virus genotype diversity is crucial to understand the emergence and spread of outbreaks, both aspects that are vital to develop effective prevention and treatment strategies. Hence, we developed an efficient method to classify virus sequences with respect to their species and sub-species (i.e. serotype and/or genotype). This tool provides an easy-to-use software implementation of this new method and was validated on a large dataset assessing the classification performance with respect to whole-genome sequences and partial-genome sequences. Available online: http://krisp.org.za/tools.php.
Assuntos
Vírus Chikungunya/isolamento & purificação , Biologia Computacional/métodos , Vírus da Dengue/isolamento & purificação , Zika virus/isolamento & purificação , Febre de Chikungunya/virologia , Vírus Chikungunya/classificação , Vírus Chikungunya/genética , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Genoma Viral , Genótipo , Filogenia , Zika virus/classificação , Zika virus/genética , Infecção por Zika virus/virologiaRESUMO
Leptospirosis is a worldwide zoonosis, responsible for more than 1 million cases and 60,000 deaths every year. Among the 13 pathogenic species of the genus Leptospira, serovars belonging to L. interrogans serogroup Icterohaemorrhagiae are considered to be the most virulent strains, and responsible for majority of the reported severe cases. Serovars Copenhageni and Icterohaemorrhagiae are major representatives of this serogroup and despite their public health relevance, little is known regarding the genetic differences between these two serovars. In this study, we analyzed the genome sequences of 67 isolates belonging to L. interrogans serovars Copenhageni and Icterohaemorrhagiae to investigate the influence of spatial and temporal variations on DNA sequence diversity. Out of the 1072 SNPs identified, 276 were in non-coding regions and 796 in coding regions. Indel analyses identified 258 indels, out of which 191 were found in coding regions and 67 in non-coding regions. Our phylogenetic analyses based on SNP dataset revealed that both serovars are closely related but showed distinct spatial clustering. However, likelihood ratio test of the indel data statistically confirmed the presence of a frameshift mutation within a homopolymeric tract of lic12008 gene (related to LPS biosynthesis) in all the L. interrogans serovar Icterohaemorrhagiae strains but not in the Copenhageni strains. Therefore, this internal indel identified can genetically distinguish L. interrogans serovar Copenhageni from serovar Icterohaemorrhagiae with high discriminatory power. To our knowledge, this is the first study to identify global sequence variations (SNPs and Indels) in L. interrogans serovars Copenhageni and Icterohaemorrhagiae.
Assuntos
DNA Bacteriano/genética , Variação Genética , Leptospira interrogans/genética , Leptospirose/microbiologia , Sorogrupo , Animais , Genoma Bacteriano/genética , Estudo de Associação Genômica Ampla , Humanos , Leptospira interrogans/isolamento & purificação , Filogenia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Virulência/genéticaRESUMO
The molecular and biological properties of HIV-1 subtype C strains from South Brazil were investigated. We sequenced gag and env fragments of viruses from 22 HIV-1-infected individuals from Porto Alegre City, which has the highest frequency of subtype C in the country. The sequences were then compared with other subtype B, C, and F strains isolated in Brazil and other countries using phylogenetic methods. Amino acid signatures were identified and correlated with phenotypic characteristics. We identified six strains with subtype C (27.3%), eight subtype B (36.4%), one subtype F (4.5%), six C/B recombinants (27.3%), and one B/F recombinant (4.5%). The Brazilian subtype C sequences formed a unique phylogenetic group and presented 6 and 18 specific amino acid signatures in gag and env, respectively. Three distinct patterns of C/B recombinants presented characteristic Brazilian amino acid substitutions. Subtype C viruses were predominantly R5 and non-syncytium-inducing, while C/B recombinants were R5/X4 and syncytium-inducing viruses. These findings suggest that subtype C viruses circulating in Brazil are the result of a unique introduction into the country. Recombination events between subtypes B and C have been occurring frequently for more than 10 years in South Brazil. Biological characterization confirms the hypothesis that subtype C is distinct from the others in the evolution of coreceptor utilization.
Assuntos
Infecções por HIV/microbiologia , HIV-1/genética , HIV-1/isolamento & purificação , Motivos de Aminoácidos , Sequência de Aminoácidos , Sequência de Bases , Brasil , Sequência Consenso , DNA Viral/análise , Produtos do Gene env/genética , Produtos do Gene gag/genética , Genes env , Genes gag , HIV-1/classificação , Humanos , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , Recombinação Genética , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Especificidade da EspécieRESUMO
We compared the genetic diversity of the Brazilian human T-cell lymphotropic virus type 1 isolates with those found in KwaZulu-Natal (KZN), South Africa, and with the genetic background of the hosts. The seroprevalence rate in KZN was 1.7%. All sequences belonged to the A subgroup. The presence of South African sequences in two different clusters from Brazil, and the finding of the beta-globin haplotype in infected hosts are consistent with the transmission of this virus from southern Africa to Brazil.
Assuntos
Evolução Molecular , Genes Virais , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Brasil/epidemiologia , Variação Genética , Globinas/genética , Infecções por HTLV-I/epidemiologia , Haplótipos , Humanos , Epidemiologia Molecular/métodos , Filogenia , Estudos Soroepidemiológicos , África do Sul , Sequências Repetidas TerminaisRESUMO
In Brazil, HTLV-2 has been detected in blood donors, in intravenous drug users (IDUs) from urban areas, and in Amerindians living in the Amazon basin. Of the three main HTLV-2 subtypes (2a, 2b, and 2d) only subtype 2a has been detected in Brazil. However, a molecular variant of subtype 2a (also called HTLV-2c) characterized by an extended Tax protein has been isolated from Brazilian blood donors, IDUs, and Indians. Here, we analyzed HTLV-2 isolates from 10 IDUs and a Chilean woman living in Salvador, Bahia, Brazil. Sequencing of env, pX, and long terminal repeat (LTR) genes demonstrated that 10 of the isolates are related to the Brazilian subtype 2a molecular variant described previously. We show that most HTLV-2a Brazilian strains comprise a phylogenetic group harboring a considerable degree of diversity within the env region but not within the LTR region. Interestingly, we demonstrated for the first time in Brazil the presence of a subtype 2a in IDUs that is closely related to the prototype Mo but distinct from the Brazilian 2a molecular variant.
Assuntos
Infecções por HTLV-II/epidemiologia , Vírus Linfotrópico T Tipo 2 Humano/classificação , Indígenas Sul-Americanos , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Brasil/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Produtos do Gene env/química , Produtos do Gene env/genética , Infecções por HTLV-II/virologia , Vírus Linfotrópico T Tipo 2 Humano/genética , Humanos , Masculino , Dados de Sequência Molecular , América do Norte/epidemiologia , Filogenia , Proteínas Oncogênicas de Retroviridae/química , Proteínas Oncogênicas de Retroviridae/genética , Análise de Sequência de DNA , Sequências Repetidas Terminais/genéticaRESUMO
To investigate serological, epidemiological, and molecular aspects of HTLV-1, HTLV-2, and HIV-1 infections in Amerindian populations in Brazil, we tested 683 and 321 sera from Tiriyo and Waiampi Indians, respectively. Both HIV-1 and HTLV-2 infections were detected at low prevalence among the Tiriyos whereas only HTLV-1 was present among the Waiampis, also at low prevalence. Analysis of the nucleotide sequence of the 631 bp of the env gene obtained from the three HTLV-2 isolates detected among the Tiriyos demonstrated by restriction fragment length polymorphism that these viruses belong to subtype IIa. Phylogenetic analysis of this same fragment showed that these sequences cluster closer to HTLV-2 isolates from intravenous drug users living in urban areas of southern Brazil than to the same gene sequence studied in another Brazilian tribe, the Kayapos. Our results confirm the distribution of Brazilian HTLV-2 sequences in a unique cluster I and cluster IIa and suggest that there is a considerable degree of diversity within this cluster. We also report for the first time HIV-1 infection among Brazilian Amerindians.
Assuntos
Anticorpos Antivirais/sangue , Infecções por HIV/virologia , HIV-1 , Infecções por HTLV-I/virologia , Infecções por HTLV-II/virologia , Vírus Linfotrópico T Tipo 1 Humano , Vírus Linfotrópico T Tipo 2 Humano , Adolescente , Adulto , Brasil/epidemiologia , Criança , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/epidemiologia , HIV-1/imunologia , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 2 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Humanos , Indígenas Sul-Americanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Dados de Sequência Molecular , Prevalência , RNA Viral/genética , Estudos SoroepidemiológicosRESUMO
The purpose of this study was to investigate the balance between transfer ribonucleic acid (tRNA) supply and demand in retrovirus-infected cells, seeking the best targets for antiretroviral therapy based on the hypothetical tRNA Inhibition Therapy (TRIT). Codon usage and tRNA gene data were retrieved from public databases. Based on logistic principles, a therapeutic score (T-score) was calculated for all sense codons, in each retrovirus-host system. Codons that are critical for viral protein translation, but not as critical for the host, have the highest T-score values. Theoretically, inactivating the cognate tRNA species should imply a severe reduction of the elongation rate during viral mRNA translation. We developed a method to predict tRNA species critical for retroviral protein synthesis. Four of the best TRIT targets in HIV-1 and HIV-2 encode Large Hydrophobic Residues (LHR), which have a central role in protein folding. One of them, codon CUA, is also a TRIT target in both HTLV-1 and HTLV-2. Therefore, a drug designed for inactivating or reducing the cytoplasmatic concentration of tRNA species with anticodon TAG could attenuate significantly both HIV and HTLV protein synthesis rates. Inversely, replacing codons ending in UA by synonymous codons should increase the expression, which is relevant for DNA vaccine design.