Binding Evolution of the Dengue Virus Envelope Against DC-SIGN: A Combined Approach of Phylogenetics and Molecular Dynamics Analyses Over 30 Years of Dengue Virus in Brazil.

The Red Queen Hypothesis (RQH), derived from Lewis Carroll's "Through the Looking-Glass", postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host-pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus-cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus-host systems and noted patterns of co-evolution. As viruses evolved receptor-binding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co-evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this ever-evolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time.

Ecological relationships of Haemagogus spegazzinii (Diptera: Culicidae) in a semiarid area of Brazil

Abstract INTRODUCTION: Haemagogus are mosquitoes with diurnal habits that live preferentially in forest areas. In Brazil, they are considered the primary vectors of wild yellow fever. METHODS: The ecological relationships between Haemagogus spegazzinii, the environment, and some of its activities in the semiarid region of Rio Grande do Norte were analyzed by collecting eggs with ovitraps, actively searching in tree holes, capturing adults in Shannon traps, and conducting an investigation for viral infections. RESULTS: A total of 2420 eggs, 271 immature specimens (larvae and pupae), and 206 adults were collected. Egg collection depended on rainfall and relative humidity, with oviposition occurring between January and May. Larvae were found in five plant species, including Tabebuia aurea (craibeira), with 160 larvae collected. We observed shared breeding sites between Hg. spegazzinii and the following species: Aedes albopictus, Aedes terrens, Culex spp., and Toxorhynchites theobaldi. Adults exhibited greater activity between 5 pm and 6 pm, when 191 (92.7%) specimens were captured, while only 1 (0.5%) was collected between 7 pm and 8 pm. The relationship between Hg. spegazzinii and rainfall was significant, with positive correlations with accumulated rainfall 5, 10, 15, 20, and 30 days before mosquito collection. We found that the species was infected with the DENV-2 virus. CONCLUSIONS: This work contributes new information on the bioecology of Hg. spegazzinii, with data on the main reproduction periods, oviposition, breeding sites, activity times, and the relationship between the species and meteorological variables in the Caatinga of northeastern Brazil.

Tityus serrulatus scorpion venom induces apoptosis in cervical cancer cell lines

Cervical cancer (CC) is classified as the fourth most common type of cancer in women worldwide and remains a serious public health problem in many underdeveloped countries. Human papillomavirus (HPV), mainly types 16 and 18, has been established as a precursory etiologic agent for this type of cancer. Several therapeutic attempts have been studied and applied, aiming at its control. However, not only do classical treatments such as chemotherapies and radiotherapies target tumor cells, but also they cause damage to several healthy cells. For these reasons, the search for new biologically active chemotherapeutic components is of great importance. In this study, we investigated the effect of Tityus serrulatus scorpion venom (TsV) on CC lines. There are very few studies exploring venom of scorpions, and, to our knowledge, no study has been conducted using the venom of the scorpion TsV for treatment of cervical cancer lines. After challenge with TsV, the MTT assay demonstrated cytotoxic effect on HeLa line. Similarly, the cell death process in HeLa analyzed by flow cytometry suggests death via caspase, since the pan-caspase inhibitor z-VAD-fmk significantly reduced the apoptotic response to the treatment. These results suggest that venom of TsV can be a potential source for the isolation of effective antiproliferative and apoptotic molecules in the treatment of CC.

Tityus serrulatus scorpion venom induces apoptosis in cervical cancer cell lines

Cervical cancer (CC) is classified as the fourth most common type of cancer in women worldwide and remains a serious public health problem in many underdeveloped countries. Human papillomavirus (HPV), mainly types 16 and 18, has been established as a precursory etiologic agent for this type of cancer. Several therapeutic attempts have been studied and applied, aiming at its control. However, not only do classical treatments such as chemotherapies and radiotherapies target tumor cells, but also they cause damage to several healthy cells. For these reasons, the search for new biologically active chemotherapeutic components is of great importance. In this study, we investigated the effect of Tityus serrulatus scorpion venom (TsV) on CC lines. There are very few studies exploring venom of scorpions, and, to our knowledge, no study has been conducted using the venom of the scorpion TsV for treatment of cervical cancer lines. After challenge with TsV, the MTT assay demonstrated cytotoxic effect on HeLa line. Similarly, the cell death process in HeLa analyzed by flow cytometry suggests death via caspase, since the pan-caspase inhibitor z-VAD-fmk significantly reduced the apoptotic response to the treatment. These results suggest that venom of TsV can be a potential source for the isolation of effective antiproliferative and apoptotic molecules in the treatment of CC.

Molecular and clinical epidemiological surveillance of dengue virus in Paraíba, Northeast Brazil

ABSTRACT INTRODUCTION: Despite being the most prevalent arboviral disease worldwide, dengue has been neglected lately. However, recent epidemics of arboviruses such as Zika and chikungunya in locations throughout the world have alerted health authorities to these diseases. This study evaluated the incidence pattern of dengue, its clinical characteristics, and co-circulation of serotypes from 2007 to 2015 in Paraiba State, Northeast Brazil. METHODS: Data on dengue cases from 2007 to 2015 were extracted from clinical reports of the National System for Notifiable Diseases [Sistema Nacional de Agravos de Notificação (SINAN)] of Brazil provided by the Paraiba Health Department. Reverse transcription polymerase chain reaction (RT-PCR) assays for dengue serotypes were carried out on plasma samples obtained from patients with suspected dengue. The data were analysed using descriptive statistics. RESULTS: According to clinical features, dengue fever [n = 39,083 (70.2%)] and dengue without warning signs [n = 15,365 (27.7%)] were the most common classifications of dengue. On RT-PCR, DENV 1 was the most commonly identified serotype (80.5%) in all years studied. Co-circulation of all four DENV serotypes was observed in 2013 and 2014. Furthermore, we observed an increase in dengue notifications in 2015, possibly due to the rise of Zika and chikungunya. CONCLUSIONS: Our findings support the hypothesis that co-circulation of the four DENV serotypes may be a reason for the increased prevalence of severe forms of dengue in the years studied. This study may contribute to directing research, health policy, and financial resources toward reducing poorly controlled epidemic diseases.

O papel da inflamação na carcinogênese induzida pelo HPV / The role of inflammation in HPV carcinogenesis

A inflamação é uma estratégia de defesa inata que evoluiu nos organismos superiores, contra agentes invasores externos e moléculas nocivas. Estudos recentes mostram que a inflamação opera como um sistema muito mais complexo do que se imaginava antes, em termos moleculares, envolvendo diversos processos na sua iniciação, regulação e resolução. Na última década, tornou-se evidente que a inflamação crônica está fortemente associada com câncer, desempenhando um papel importante na tumorigênese. Uma das causas de inflamação crônica são as infecções persistentes por agentes patogênicos virais, com destaque para o papilomavírus humano (HPV). A ligação entre a inflamação crônica decorrente da infecção persistente por agentes infecciosos e o câncer está atualmente sendo apontada como um dos mecanismos-chave para o controle do surgimento de novos casos de carcinomas. Por esse motivo, consultamos os bancos de dados eletrônicos PubMed/Medline, Lilacs, Embase e SciELO, sem restrição linguística, à procura de artigos que abordassem avanços recentes sobre os mecanismos envolvidos na inflamação, sua participação no processo de carcinogênese, com ênfase na correlação entre inflamação e o desenvolvimento do câncer associado ao HPV, os quais foram incluídos na presente revisão.(AU)

Inflammation is an innate defense strategy that evolved in higher organisms against external invaders and harmful molecules. Recent studies show that inflammation operates as a much more complex system than imagined before, in molecular terms, involving many processes in its initiation, regulation and resolution. In the very last decade, it has become evident that chronic inflammation is strongly associated with cancer and plays an important role in tumorigenesis. One of the causes of chronic inflammation are persistent infections by viral pathogens, particularly human papillomavirus (HPV). The link between chronic inflammation resulting from persistent infection by infectious agents and cancer is currently being suggested as a key mechanism for controlling the appearance of new cases of carcinoma. Therefore, we consult electronic databases such as PubMed/Medline, Lilacs, Embase and SciELO, without language restriction, looking for papers discussing recent advances on the mechanisms involved in inflammation, their participation in the process of carcinogenesis, with emphasis on the correlation between inflammation and the development of cancer associated with HPV, which were included in this review.(AU)

Dengue virus type 3 in Brazil: a phylogenetic perspective

Circulation of a new dengue virus (DENV)-3 genotype was recently described in Brazil and Colombia, but the precise classification of this genotype has been controversial. Here we perform phylogenetic and nucleotide-distance analyses of the envelope gene, which support the subdivision of DENV-3 strains into five distinct genotypes (GI to GV) and confirm the classification of the new South American genotype as GV. The extremely low genetic distances between Brazilian GV strains and the prototype Philippines/L11423 GV strain isolated in 1956 raise important questions regarding the origin of GV in South America.

Vírus dengue sorotipo 3 (DENV-3) no Brasil: estudos sobre patogenia, sítios de replicação, filogenia e evolução molecular / Dengue virus serotype 3 (DENVER-3) in Brazil: studies on pathogenesis, sites of replication, phylogeny and molecular evolution

Dengue é uma importante arbovirose (arthropod-borne virus) e constitui um grave problema de saúde pública não só no Brasil, mas também nos países de clima tropical. O Aedes aegypti é o principal vetor dos vírus dengue (DENV) e está presente na maioria dos países entre as latitudes 35ºN e 35ºS. Neste trabalho, apresentamos quatro estudos. No primeiro estudo, analisamos os níveis de RNA viral dos DENV-3 e sua correlação com o tipo de infecção (primária ou secundária) em casos fatais e não fatais por dengue, ocorridos no estado do Rio de Janeiro, 2002. O grupo de casos fatais apresentou uma média de título viral significativamente mais elevada do que o grupo de casos não fatais. Considerando que infecções primárias foram confirmadas entre os casos fatais (52,1 por cento), a teoria da infecção sequencial por si só não explica todos os casos graves da doença. Estes resultados sugerem que altos níveis de DENV-3 podem ter contribuído para a forma grave do dengue no Rio de Janeiro, 2002. No segundo estudo, diferentes métodos de diagnóstico foram aplicados para investigar a presença dos DENV em amostras de tecidos humanos obtidos a partir de casos fatais (n=29), ocorridos durante a grande epidemia em 2002 no estado do Rio de Janeiro, Brasil. A combinação de quatro métodos permitiu a confirmação da infecção por DENV-3 em 26 (89,6 por cento) dos casos suspeitos. O isolamento viral foi obtido em 2,7 (2/74) das amostras, a partir da inoculação em cultura de células C6/36. A técnica de nested RT-PCR permitiu a identificação do DENV-3 em 30,5 por cento (22/72) das amostras analisadas. O método de RT-PCR em tempo real possuiu maior sensibilidade, detectando o RNA viral em 58,4 por cento (45/77) dos espécimes clínicos, incluindo fígado (n=18), pulmão (n=8) , baço (n=8), cérebro (n=6), rim (n=3), medula óssea (n=1) e coração (n=1). A técnica de imunohistoquímica detectou o antígeno viral em 44 por cento (26/59) das amostras analisadas. A precisão e eficácia...América do Sul.

Dengue viruses in Brazil, 1986-2006

A total of 4 243 049 dengue cases have been reported in Brazil between 1981 and 2006, including 5 817 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and a total of 338 fatal cases. Although all Brazilian regions have been affected, the Northeast and Southeast regions have registered the highest number of notifications. DENV-1 and DENV-4 were isolated for the first time in the Amazon region of Brazil in 1981 and 1982. The disease became a nationwide public health problem following outbreaks of DENV-1 and DENV-2 in the state of Rio de Janeiro in 1986 and 1990, respectively. The introduction of DENV-3 in 2000, also in the state of Rio de Janeiro, led to a severe epidemic with 288 245 reported dengue cases, including 91 deaths. Virus strains that were typed during the 2002 epidemic show that DENV-3 has displaced other dengue virus serotypes and entered new areas, a finding that warrants closer evaluation. Unusual clinical symptoms, including central nervous system involvement, have been observed in dengue patients in at least three regions of the country.

En Brasil se han notificado 4 243 049 casos de dengue entre 1981 y 2006, de ellos 5 817 casos de dengue hemorrágico/síndrome de choque por dengue (DH/SCD) y un total de 338 casos mortales. A pesar de que la enfermedad ha afectado a todas las regiones brasileñas, el mayor número de casos se ha notificado en las regiones nororiental y suroriental. Los virus del dengue (DENV) 1 y 4 se aislaron por primera vez en la región amazónica de Brasil en 1981 y 1982. La enfermedad se convirtió en un problema nacional de salud pública después de los brotes de DENV-1 y DENV-2 en el Estado de Río de Janeiro en 1986 y 1990, respectivamente. La introducción del DENV-3 en 2000, también en el Estado de Río de Janeiro, llevó a una grave epidemia con 288 245 casos notificados de dengue y 91 muertes. Las cepas del virus identificadas durante la epidemia de 2002 demostraron que el DENV-3 ha desplazado a los otros serotipos y se ha expandido a nuevas zonas, algo que merece una evaluación más profunda. En los pacientes con dengue de al menos tres regiones del país se han observado síntomas clínicos atípicos, entre ellos alteraciones del sistema nervioso central.

Concurrent infection with dengue virus type-2 and DENV-3 in a patient from Ceará, Brazil

Dengue outbreaks have occurred in several regions in Brazil and cocirculating dengue virus type 1 (DENV-1), DENV-2, and DENV-3 have been frequently observed. Dual infection by DENV-2 and DENV-3 was identified by type-specific indirect immunofluorescence assay and confirmed by reverse transcription polymerase chain reaction in a patient in Ceará with a mild disease. This is the first documented case of simultaneous infection with DENV-2 and DENV-3 in Brazil. Sequencing confirmed DENV-2 and DENV-3 (South-East/American) genotype III and (SriLanka/India), genotype III respectively.

Implantação da técnica de PCR em tempo real (sistema taqman) para dengue do tipo 3 (DENV-3) e vigilância virológica no Estado do Rio de Janeiro / Implantation of the technique of PCR in real time (system taqman) for affection of type (3 DENV-3) and virological monitoring in the State of Rio De Janeiro

Neste estudo são apresentados a implantação da técnica de PCR em tempo real (Sistema TaqMan™) para o vírus dengue tipo 3 (DENV-3), a qual constitui uma nova abordagem no diagnóstico de dengue no país. Esta técnica foi aplicada a 30 amostras de fígado provenientes de 28 casos fatais ocorridos durante a epidemia de dengue de 2002 no estado do Rio de Janeiro, sendo o vírus DENV-3 o único sorotipo identificado e admitido como o agente etiológico daquela casuística. A positividade dos casos por esta nova metodologia 64,2 por cento (18/28), foi superior quando comparados a outras metodologias como o PCR convencional (RT-PCR) que confirmou 29,6 por cento (8/27) e o isolamento viral 7,6 por cento (2/26). Na mesma população a imunohistoquímica confirmou 63,6 por cento (14/22) dos casos. Esses dados demonstram a importância do PCR em tempo real em tecidos na confirmação de casos fatais suspeitos de dengue e confirmou seis casos os quais resultaram negativos por outros métodos. A Vigilância Virológica no período 2004-2005 envolveu 839 casos suspeitos de dengue sendo confirmados 4 por cento (34/839) considerando-se o isolamento viral e/ou RT-PCR. Considerando-se cada metodologia, o isolamento viral confirmou 0,4 por cento (3/723) e o RT-PCR 3,8 por cento (31/815). O DENV-3 foi o único sorotipo identificado no período 2004-2005. Entretanto, a maior circulação do vírus ocorreu em 2005 com dois surtos, um deles no município de Campos dos Goytacazes (Região Norte Fluminense) e o outro no município do Rio de Janeiro, com dois óbitos confirmados. A caracterização genética das amostras confirmou o genótipo III, o mesmo circulante até o momento no estado do Rio de Janeiro.