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1.
Braz. j. biol ; 83: e246230, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1339369

RESUMO

Abstract Dengue fever vectored by the mosquito Aedes aegypti is one of the most rapidly spreading insect-borne diseases. Current reliance of dengue vector control is mostly on chemical insecticides. Growing insecticide resistance in the primary mosquito vector, Aedes aegypti, limits the effectiveness of vector control through chemical insecticides. These chemical insecticides also have negative environmental impacts on animals, plants and human health. Myco-biocontrol agents are naturally occurring organisms and are found to be less damaging to the environment as compared to chemical insecticides. In the present study, entomopathogenic potential of local strains of fungi isolated from soil was assessed for the control of dengue vector. Local fungal isolates presents better alternative to introducing a foreign biocontrol strain, as they may be better adapted to environmental conditions of the area to survive and may have more entomopathogenic efficacy against target organism. Larvicidal efficacy of Fusarium equiseti and Fusarium proliferatum was evaluated against Aedes aegypti. Local strains of F. equiseti (MK371718) and F. proliferatum (MK371715) were isolated from the soil of Changa Manga Forest, Pakistan by using insect bait method. Larvicidal activity of two Fusarium spp. was tested against forth instar larvae of A. aegypti in the laboratory, using concentrations 105, 106, 107 and 108 conidia /ml. LC50 values for F. equiseti after 24h, 48h, 72h and 96h of exposure were recorded as 3.8x 108, 2.9x107, 2.0x107, and 7.1x106 conidia /ml respectively while LC50 values for F. proliferatum were recorded as 1.21x108, 9.6x107, 4.2x107, 2.6x107 conidia /ml respectively after 24h, 48h, 72h and 96h of exposure. The results indicate that among two fungal strains F. equiseti was found to be more effective in terms of its larvicidal activity than F. proliferatum against larvae of A. aegypti.


Resumo A dengue transmitida pelo mosquito Aedes aegypti é uma das doenças transmitidas por insetos de propagação mais rápida. A dependência atual do controle do vetor da dengue é principalmente de inseticidas químicos. O aumento da resistência a inseticidas no principal vetor do mosquito, Aedes aegypti, limita a eficácia do controle do vetor por meio de inseticidas químicos. Esses inseticidas químicos também têm impactos ambientais negativos sobre os animais, plantas e saúde humana. Os agentes de micobiocontrole são organismos que ocorrem naturalmente e são menos prejudiciais ao meio ambiente em comparação com os inseticidas químicos. No presente estudo, avaliou-se o potencial entomopatogênico de cepas locais de fungos isolados do solo para o controle do vetor da dengue. Isolados de fungos locais apresentam melhor alternativa para a introdução de uma cepa de biocontrole estrangeira, pois podem ser mais bem adaptados às condições ambientais da área para sobreviver e podem ter maior eficácia entomopatogênica contra o organismo-alvo. A eficácia larvicida de Fusarium equiseti e Fusarium proliferatum foi avaliada contra Aedes aegypti. Cepas locais de F. equiseti (MK371718) e F. proliferatum (MK371715) foram isoladas do solo de Changa Manga Forest, Paquistão, usando o método de isca para insetos. Atividade larvicida de dois Fusarium spp. foi testado contra larvas de quarto ínstar de A. aegypti em laboratório, nas concentrações 105, 106, 107 e 108 conídios / ml. Os valores de LC50 para F. equiseti após 24 h, 48 h, 72 h e 96 h de exposição foram registrados como 3,8x 108, 2,9x107, 2,0x107 e 7,1x106 conídios / ml, respectivamente, enquanto os valores de LC50 para F. proliferatum foram registrados como 1,21x108, 9,6 x107, 4,2x107, 2,6x107 conídios / ml, respectivamente, após 24 h, 48 h, 72 h e 96 h de exposição. Os resultados indicam que entre duas cepas de fungos F. equiseti se mostrou mais eficaz em termos de atividade larvicida do que F. proliferatum contra larvas de A. aegypti.


Assuntos
Humanos , Animais , Aedes , Fusarium , Inseticidas/farmacologia , Paquistão , Solo , Extratos Vegetais , Florestas , Mosquitos Vetores , Larva
2.
Braz. j. biol ; 83: e247539, 2023. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1278542

RESUMO

Abstract Numerous studies have investigated the chemical composition and biological activities of essential oils from different Citrus species fruit peel, leaves and flowers. This paper aims to investigate the chemical composition, larvicidal and antileishmanial activities of essential oil from Citrus reticulata fruit peel (CR-EO). CR-EO was obtained by hydrodistillation in a Clevenger-type apparatus and its chemical composition was analyzed by GC-MS and GC-FID. Limonene (85.7%), ɣ-terpinene (6.7%) and myrcene (2.1%) were identified as its major components. CR-EO showed high activity against promastigote forms of Leishmania amazonensis (IC50 = 8.23 µg/mL). CR-EO also exhibited high larvicidal activity against third instar Aedes aegypti larvae at a lethal concentration (LC50 = 58.35 µg/mL) and 100% mortality at 150 µg/mL. This study suggests, for the first time, the potential use of CR-EO against this important mosquito-borne viral disease caused by the genus Aedes.


Resumo Numerosos estudos têm investigado a composição química e as atividades biológicas de óleos essenciais extraídos de cascas dos frutos, folhas e flores de diferentes espécies de Citrus. Este trabalho tem como objetivo investigar a composição química e as atividades larvicida e leishmanicida in vitro do óleo essencial das cascas dos frutos de Citrus reticulata (CR-EO). CR-EO foi obtido pela técnica de extração em aparelho Clevenger e sua composição química foi determinada por CG-EM e CG-DIC. Limoneno (85,7%), ɣ-terpineno (6,7%) and mirceno (2,1%) foram identificados como os constituintes majoritários. CR-EO mostrou alta atividade contra as formas promastigota de Leishmania amazonensis (CI50 = 8,23 µg/mL). CR-EO também exibiu alta atividade larvicida contra as larvas do terceiro estágio do Aedes aegypti com concentração letal (CL50 = 58,35 µg/mL) e mortalidade de 100% em 150 µg/mL. Este estudo sugere, pela primeira vez, o uso potencial de CR-EO contra esta importante doença viral transmitida por mosquitos do gênero Aedes.


Assuntos
Animais , Óleos Voláteis/farmacologia , Citrus , Aedes , Inseticidas/farmacologia , Frutas , Larva
3.
Braz. j. biol ; 83: e244647, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1278527

RESUMO

Abstract The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 μg mL-1 were obtained for the essential oil and 4.36 μg mL-1 for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 μg mL-1 for the essential oil of citronella and 86.30 μg mL-1 for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.


Resumo O óleo essencial de citronela (Cymbopogon winterianus) possui diversas atividades biológicas, entre elas a ação repelente a insetos. Alguns estudos mostraram que os ésteres do ácido cinâmico podem ser aplicados como pesticidas naturais, inseticidas e fungicidas. Nesse contexto, o objetivo do presente trabalho foi avaliar a produção de ésteres a partir do óleo essencial de citronela com ácido cinâmico via esterificação enzimática. Além disso, foi investigada a toxicidade do óleo essencial antes e após a esterificação contra Artemia salina e a ação larvicida sobre Aedes aegypti. Os ésteres foram produzidos utilizando ácido cinâmico como agente acilante e óleo essencial de citronela (3: 1) em heptano e 15% em peso da enzima NS 88011 como biocatalisadores, a 70 ° C e 150 rpm. As taxas de conversão de cinamatos de citronelil e geranil foram 58,7 e 69,0% para NS 88011, respectivamente. Para a toxicidade sobre Artemia salina foram obtidos CL50 de 5,29 μg mL-1 para o óleo essencial e 4,36 μg mL-1 para os óleos esterificados com NS 88011. Na atividade inseticida contra larvas de Aedes aegypti, obteve-se CL50 de 111,84 μg mL-1 para o óleo essencial de citronela e 86,30 μg mL-1 para os óleos esterificados com a enzima NS 88011, indicando alta toxicidade dos ésteres. Os resultados demonstraram que as amostras avaliadas apresentam potencial de aplicação como bioinseticida.


Assuntos
Animais , Óleos Voláteis/toxicidade , Aedes , Cymbopogon , Repelentes de Insetos , Inseticidas/toxicidade , Esterificação , Larva
4.
Braz. j. biol ; 83: e244966, 2023. tab
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1360197

RESUMO

Abstract Dengue fever (DF) is increasingly recognized as one of the world's major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control.


Resumo A dengue (DF) é cada vez mais reconhecida como uma das principais doenças transmitidas por mosquitos do mundo e causa significativa morbidade e mortalidade em países tropicais e subtropicais. A dengue é endêmica na maior parte do Paquistão e continua a ser um problema de saúde pública. Conhecimento, atitude e práticas podem desempenhar papel importante no manejo da doença. O presente estudo teve como objetivo determinar o nível de conhecimento, atitude e práticas em relação à dengue entre os profissionais de saúde, para estudar o nível de conhecimento e atitude com as práticas preventivas da dengue. Um estudo transversal foi realizado com médicos dos quatro distritos da região de Malakand de outubro a novembro de 2019. Um questionário pré-estruturado foi usado para coletar dados de médicos. Os dados foram analisados no Graph Pad versão 5. Valor significativo foi considerado quando menor que 0,05 (com intervalo de confiança de 95%). Os resultados revelaram que a maioria dos participantes já viu o vetor da dengue (62%), sendo a mídia a fonte de informação mais citada. Quase 81,2% dos participantes sabiam que a transmissão da dengue é por picada de mosquito. Constatou-se que as práticas baseadas em medidas preventivas se concentravam predominantemente na prevenção de picadas de mosquitos, e não na eliminação de criadouros. Embora o conhecimento sobre DF e medidas de controle de mosquitos fosse bastante elevado entre os médicos, esse conhecimento não foi colocado em prática. Mais estudos são necessários para conscientizar a população sobre a dengue e seu vetor, a fim de se obter prevenção e controle.

5.
Front Microbiol ; 13: 933482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090120

RESUMO

Dengue virus (DENV) is a highly prevalent vector-borne virus that causes life-threatening illnesses to humans worldwide. The development of a tool to control vector populations has the potential to reduce the burden of DENV. Toxic sugar bait (TSB) provides a form of vector control that takes advantage of the sugar-feeding behavior of adult mosquitoes. However, studies on the effect of ingestion of toxins in TSB on vector competence and vectorial capacity for viruses are lacking. This study evaluated vector competence for DENV serotype-1 of Aedes albopictus at 7 and 14 days post-ingestion of TSB formulated with spinosad (of bacteria origin) as an oral toxin. Our results and others were modeled to estimate effects on Ae. albopictus vectorial capacity for DENV. Ingestion of TSB caused a reduction in survival of females, but increased mosquito susceptibility to DENV infection, disseminated infection, and transmission. However, this increase in vector competence was obviated by the reduction in survival, leading to a lower predicted vectorial capacity. The findings of this study highlight the importance of evaluating the net impact of TSB ingestion on epidemiological parameters of vectorial capacity in the context of vector control efforts to reduce the risk of transmission of vector-borne viruses.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36090297

RESUMO

Invasive fungal rhinosinusitis was seen to rise to epidemic levels after the 2nd wave of ongoing Covid pandemic, especially in tropical countries, maximally in India. A similar trend is being observed for cases who have recently recovered from dengue virus infection. Post dengue invasive fungal infection is a new presentation and any associations between it and Covid pandemic need to be studied in detail to help prepare for any complications. 3 patients presented to the out-patient department of E.N.T at a tertiary level teaching hospital in East India with complains similar to rhinosinusitis. These patients were then evaluated and diagnosed to be infected from Mucormycosis and Aspergillosis fungal sinusitis after which they were managed with surgical debridement and systemic antifungal therapy. All had a recent history of recovery from Dengue virus infection and a possible association could be suspected. 3 patients presented with complains of pain over upper jaw with orbital swelling and loss of vision developing over a period of 24 days. Two of them had ulceration of hard palate. They were then subjected to Contrast MRI along with CT scan of the Paranasal sinuses which depicted pansinus involvement with intracranial extension in two patients. These were then planned for diagnostic nasal endoscopies along with biopsies which turned out to be Invasive fungal sinusitis in the form of Aspergillosis and Mucormycosis. All the 3 patients had recent history of recovery from Dengue virus infection and did not have any other co-morbidities. Covid Associated Mucormycosis (CAM) is a well-known entity now but no reports of Dengue associated Invasive fungal sinusitis are yet reported. Whether this new phenomenon has anything to do with the interactions between dengue virus and coronavirus is not known at present and needs to be studied in detail so appropriate management protocols can be formulated.

7.
3 Biotech ; 12(10): 268, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36091089

RESUMO

The aim of the present study was to determine whether the serum ferritin, the biomarker of an acute phase reactant and the gall bladder wall edema, an early indicator of capillary leakage can predict the severity of dengue fever. This study included 131 patients, who were between the age group of 18-80 years. The patients presented to our department with an acute illness, within the first four days of high temperature. The statistical analysis of this study was performed by using the Chi-square and independent Student's t tests. The diagnostic markers are considered statistically significant, if the serum ferritin level is higher than 500 ng/ml and the gall bladder wall thickness is more than 3 mm. The present study observed that, 39 patients (89%) who had severe dengue (n = 44) revealed a significant gall bladder wall thickening, and this correlation was significant statistically (p < 0.000). It was also observed that, the ferritin levels have a highly significant positive correlation with the severity of dengue. The severe dengue patients had a mean ferritin level of 9125.34 µg/l, whereas the non-severe group had 4271 µg/l. This comparison was also statistically significant, as the p value was 0.003. We report that the serum ferritin levels have a highly significant positive correlation with the severity of dengue. The gall bladder wall edema during the third and fourth day of the illness was also associated with severe dengue. However, diffuse gall bladder wall thickening and high serum ferritin levels are also reported in various other conditions and their exact cause have to be determined by the correlation of associated clinical findings and imaging features.

8.
Infect Dis Model ; 7(3): 510-525, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36091345

RESUMO

Dengue is a harmful tropical disease that causes death to many people. Currently, the dengue vaccine development is still at an early stage, and only intervention methods exist after dengue cases increase. Thus, previously, two scientific experimental field studies were conducted in producing a dengue outbreak forecasting model as an early warning system. Successfully, an Autoregressive Distributed Lag (ADL) Model was developed using three factors: the epidemiological, entomological, and environmental with an accuracy of 85%; but a higher percentage is required in minimizing the error for the model to be useful. Hence, this study aimed to develop a practical and cost-effective dengue outbreak forecasting model with at least 90% accuracy to be embedded in an early warning computer system using the Internet of Things (IoT) approach. Eighty-one weeks of time series data of the three factors were used in six forecasting models, which were Autoregressive Distributed Lag (ADL), Hierarchical Forecasting (Bottom-up and Optimal combination) and three Machine Learning methods: (Artificial Neural Network (ANN), Support Vector Machine (SVM) and Random Forest). Five error measures were used to evaluate the consistency performance of the models in order to ensure model performance. The findings indicated Random Forest outperformed the other models with an accuracy of 95% when including all three factors. But practically, collecting mosquito related data (the entomological factor) was very costly and time consuming. Thus, it was removed from the model, and the accuracy dropped to 92% but still high enough to be of practical use, i.e., beyond 90%. However, the practical ground operationalization of the early warning system also requires several rain gauges to be located at the dengue hot spots due to localized rainfall. Hence, further analysis was conducted in determining the location of the rain gauges. This has led to the recommendation that the rain gauges should be located about 3-4 km apart at the dengue hot spots to ensure the accuracy of the rainfall data to be included in the dengue outbreak forecasting model so that it can be embedded in the early warning system. Therefore, this early warning system can save lives, and prevention is better than cure.

10.
Clin Exp Hepatol ; 8(2): 161-169, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36092760

RESUMO

Introduction: Dengue and hepatitis B are viral infections endemic to tropical areas with liver consequences. However, coinfection cases have been poorly documented worldwide and especially on the African continent. This study aimed at analysing the seroepidemiology of dengue-hepatitis B co-infection in patients recruited at the Regional Hospital of Ngaoundere (Cameroon). Material and methods: A cross-sectional study was conducted among 225 patients, aged 15-55 years, enrolled at the Laboratory service of Ngaoundere Regional Hospital from 25 September to 10 December 2021. HBsAg and dengue infection were diagnosed using the serological rapid tests. Part of the blood samples was used to quantify lipid profile and liver function parameters. Results: Of the 225 patients recruited, 22.22% (50) tested positive for hepatitis B and 18.18% (38/202) were positive for dengue fever, with a dengue-hepatitis B coinfection rate of 4.95% (10/202). Coinfected patients were not significantly associated with liver injury compared to monoinfected patients. However, they displayed a higher risk of presenting abnormal γ-glutamyltransferase (γ-GT) (RR = 1.74, 90% vs. 51.51%) and alanine aminotransferase (ALT) values (RR = 1.52, 60% vs. 39.39%) compared to the monoinfected group. Also, there was no difference in total and direct bilirubin between patient groups. The mean triglyceride and low-density lipoprotein (LDL) cholesterol levels and coronary heart index values were higher in the coinfected group than in the monoinfected group, but without significance. Conclusions: Taken altogether, these findings suggest that the presence of hepatitis B in dengue patients may slightly affect the liver's metabolic functions. Clinical surveillance of this coinfection is therefore required to avoid further liver complications.

11.
SAR QSAR Environ Res ; 33(9): 729-751, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36106833

RESUMO

Spraying repellents on clothing limits toxicity and allergy problems that can occur when the repellents are directly applied to skin. This also allows the use of higher doses to ensure longer lasting effects. As the number of repellents available on the market is limited, it is necessary to propose new ones, especially by using in silico methods that reduce costs and time. In this context SAR models were built from a dataset of 2027 chemicals for which repellent activity on clothing was measured against Aedes aegypti. The interest of using either the ECFP or MACCS fingerprints as input neurons of a three-layer perceptron was evaluated. Transformation of MACCS bit strings into disjunctive tables led to interesting results. Models obtained with both types of fingerprints were compared to a model including physicochemical and topological descriptors.


Assuntos
Aedes , Repelentes de Insetos , Animais , Vestuário , Redes Neurais de Computação , Relação Quantitativa Estrutura-Atividade
12.
Int Immunopharmacol ; 112: 109082, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36108401

RESUMO

BACKGROUND: The dengue is a vector borne viral infection in humans. Bite of mosquito infected with a dengue virus transmits the disease. The neutrophils support more to the innate immune response by switching to infected tissues and triggering immunomodulatory mechanisms including the release of proteases and host defence peptides. METHODS: Cell viability by MTT and trypan blue dye exclusion assay, bright field microscopy for assessment of cell morphology, cytokines measurements by ELISA, estimation of protein by Bradford assay were done. Assessments of matrix metalloproteinase genes mRNA expressions were done using real-time PCR. RESULTS: In the present study, we have for the first time unveiled that, NS1 antigen of dengue type-2 serotype, induce and stimulate the neutrophils cells to express high levels of matrix metalloproteases. NS1 exposure of HL-60 cells differentiated to neutrophils affected cell morphology and in 24 h of exposure. We have demonstrated that, the NS1 antigen has induced MMP-2, MMP-14 and MMP-9 expressions in neutrophils in a 24hrs exposure time. NS1 exposure has also further upregulated MMP-1, MMP-13, and MMP-8 expressions in neutrophils in a 24hrs exposure time. Notably, treatment with atorvastatin concentrations downregulated the expression profile of the all matrix metalloprotease significantly. Importantly, NS1 antigen has significantly increased the IL-6, IL-13 release by the HL,60 cells which was reversed by atorvastatin. On the other hand, NS1 exposure enhanced the mRNA expressions of VEGF-A and VEGF-D which was reversed by atorvastatin. However, we found that, NS1 exposure reduced the mRNA expressions profile of VEGF-C, which was reversed by atorvastatin. CONCLUSION: In conclusion, we report that, neutrophils associated matrix metalloprotease are involved in the pathogenesis of dengue viral disease. VEGF growth factors may also be released by the neutrophils which may subsequently participate in the endothelial dysfunctions leading to dengue shock syndrome.

13.
Int J Public Health ; 67: 1604809, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111200

RESUMO

Objectives: This study intends to evaluate the Dhaka city residents' individual views toward DF. Methods: A cross-sectional survey used google forms for collecting data. Python and RStudio were used for data management and analysis. Kruskal-Wallis or Mann-Whitney U test and logistic regression models were performed, where appropriate. Results: In total 1008 individuals participated in a pre-tested KAP survey. More than 20% reported being affected by DF before the survey, where they rated their current places as being moderately safe (43%). In terms of DF control, 65% had good knowledge, and 68% reported good practice, whereas they demonstrated an overall good attitude. The increased knowledge of individuals could contribute to behavioral changes regarding DF. Female residents demonstrated better DF attitudes (OR: 0.69; p < 0.05) and practices (OR: 0.66; p < 0.01) compared to male residents. Mixed unit residents had poor KAP levels. Educational attainment can also play an essential role in enhancing the attitude level. Conclusion: Overall, dengue surveillance activities with sufficient campaigns are required for behavioral change in Dhaka city. This information could be integrated into other DF-affected countries' strategies against dengue outbreaks.


Assuntos
Dengue , Bangladesh/epidemiologia , Estudos Transversais , Dengue/epidemiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Inquéritos e Questionários
14.
PLoS Pathog ; 18(9): e1010427, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36121894

RESUMO

Dengue viruses (DENV) are expanding global pathogens that are transmitted through the bite of mosquitoes, mostly Aedes aegypti. As RNA viruses, DENV rely on RNA-binding proteins (RBPs) to complete their life cycle. Alternatively, RBPs can act as restriction factors that prevent DENV multiplication. While the importance of RBPs is well-supported in humans, there is a dearth of information about their influence on DENV transmission by mosquitoes. Such knowledge could be harnessed to design novel, effective interventions against DENV. Here, we successfully adapted RNA-affinity chromatography coupled with mass spectrometry-a technique initially developed in mammalian cells-to identify RBPs in Ae. aegypti cells. We identified fourteen RBPs interacting with DENV serotype 2 3'UTR, which is involved in the viral multiplication and produces subgenomic flaviviral RNA (sfRNA). We validated the RNA affinity results for two RBPs by confirming that AePur binds the 3'UTR, whereas AeStaufen interacts with both 3'UTR and sfRNA. Using in vivo functional evaluation, we determined that RBPs like AeRan, AeExoRNase, and AeRNase have pro-viral functions, whereas AeGTPase, AeAtu, and AePur have anti-viral functions in mosquitoes. Furthermore, we showed that human and mosquito Pur homologs have a shared affinity to DENV2 RNA, although the anti-viral effect is specific to the mosquito protein. Importantly, we revealed that AeStaufen mediates a reduction of gRNA and sfRNA copies in several mosquito tissues, including the salivary glands and that AeStaufen-mediated sfRNA reduction diminishes the concentration of transmission-enhancing sfRNA in saliva, thereby revealing AeStaufen's role in DENV transmission. By characterizing the first RBPs that associate with DENV2 3'UTR in mosquitoes, our study unravels new pro- and anti-viral targets for the design of novel therapeutic interventions as well as provides foundation for studying the role of RBPs in virus-vector interactions.

15.
Autophagy ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36126167

RESUMO

NLRC5 has been reported to be involved in antiviral immunity; however, the underlying mechanism remains poorly understood. Here, we investigated the functional role of NLRC5 in the infection of a flavivirus, dengue virus (DENV). We found that expression of NLRC5 was strongly induced by virus infection and IFNB or IFNG stimulation in different cell lines. Overexpression of NLRC5 remarkably suppressed DENV infection, whereas knockout of NLRC5 led to a significant increase in DENV infection. Mechanistic study revealed that NLRC5 interacted with the viral nonstructural protein 3 (NS3) protease domain and mediated degradation of NS3 through a ubiquitin-dependent selective macroautophagy/autophagy pathway. We demonstrated that NLRC5 recruited the E3 ubiquitin ligase CUL2 (cullin 2) to catalyze K48-linked poly-ubiquitination of the NS3 protease domain, which subsequently served as a recognition signal for cargo receptor TOLLIP-mediated selective autophagic degradation. Together, we have demonstrated that NLRC5 exerted an antiviral effect by mediating the degradation of a multifunctional protein of DENV, providing a novel antiviral signal axis of NLRC5-CUL2-NS3-TOLLIP. This study expands our understanding of the regulatory network of NLRC5 in the host defense against virus infection.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36125197

RESUMO

Dengue virus (DENV) was discovered by P. M. Ashburn and Charles F. Craig in 1907. Evidence of dengue-like illness was observed before 1907 and DENV epidemics have been reported from different parts of the world since then, with increased morbidity rates every year. DENV typically causes a febrile illness that ranges from mild asymptomatic infection to fatal dengue haemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). Host mechanisms through which mild infection progresses to the fatal forms are still unknown. Few factors have been associated to aid severe disease acquisition, DENV non-structural 1 (NS1) protein being one of them. NS1 is a highly conserved glycoprotein among the Flavivirus and is often used as a biomarker for dengue diagnosis. This review focuses on assessing the role of NS1 in severe dengue. In this review, hospital-based studies on the association of dengue NS1 with severe dengue from all over the world have been assessed and analysed and the majority of the studies positively correlate high NS1 levels with DHF/DSS acquisition. The review also discusses a few experimental studies on NS1 that have shown it contributes to dengue pathogenesis. This review assesses the role of NS1 and disease severity from hospital-based studies and aims to provide better insights on the kinetics and dynamics of DENV infection with respect to NS1 for a better understanding of the role of NS1 in dengue.

18.
JCI Insight ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36125898

RESUMO

Diabetes mellitus (DM) is highly comorbid with severe dengue diseases; however, the underlying mechanisms are unclear. DM patients display a 1.61-fold increased risk of developing dengue hemorrhagic fever. In search of host factors involved in DENV infection, this study utilizes high glucose (HG) treatment and shows that HG increases viral protein expression and virion release but has no effects on the early stages of viral infection. Following HG stimulation, DEN-Luc-transfected assay and cellular replicon-based assay display increased viral translation, while using the glucose uptake inhibitor phloretin blocks this effect. HG treatment increases the translational factor poly(A)-binding protein (PABP) in a glucose transporter-associated PI3K/AKT-regulated manner. Silencing PABP significantly decreases HG-prompted virion production. HG enhances the formation of the PABP-eIF4G complex, which is regulated by protein-disulfide isomerase. Hyperglycemia increases PABP expression, mortality, viral protein expression, and viral loads in streptozotocin-induced DM mice. Overall, hyperglycemic stress facilitates DENV infection by strengthening PABP-mediated viral translation.

19.
Ann Med Surg (Lond) ; 81: 104535, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36065431

RESUMO

With the sharp rise in dengue cases across the state and the ongoing COVID-19 pandemic, it is crucial to pay attention to the common misbelieves among the population about dengue. It should be considered to actively spread awareness about the disease to bust the common myths associated with it. A few common myths include that it is a contagious disease, or it is a milder infection than COVID-19, so it's not taken more seriously, or that one cannot be coinfected with both dengue and COVID-19 at one time. We propose that accurate information about dengue can be spread through community education through televisions and social media to cater to the targeted audience. In addition to that, awareness campaigns in rural areas should be planned to help the masses understand the pathogenesis of the diseases and play a role in limiting the transmission.

20.
Curr Opin Infect Dis ; 35(5): 390-396, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36098260

RESUMO

PURPOSE OF REVIEW: Dengue vaccine development is a high public health priority. To date, no dengue vaccine is in widespread use. Here we review the challenges in dengue development and the latest results for the second-generation dengue vaccines. RECENT FINDINGS: The biggest hurdle is the immunological interaction between the four antigenically distinct dengue serotypes. The advantages of second-generation dengue vaccines are the inclusion of nonstructural proteins of the dengue backbone and a more convenient dosing with reduced numbers of doses needed. SUMMARY: Although dengue-primed individuals can already benefit from vaccination with the first licensed dengue vaccine CYD-TDV, the public health need for the dengue-naive population has not yet been met. The urgent need remains to identify correlates of both protection and enhancement; until such correlates have been identified, all second-generation dengue vaccines still need to go through full phase 3 trials. The 5-year efficacy and safety data for both second-generation dengue vaccines are imminent.


Assuntos
Vacinas contra Dengue , Humanos , Saúde Pública , Vacinação/métodos
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