Dengue Virus and Other Flaviviruses (Zika): Biology, Pathogenesis, Epidemiology, and Vaccine Development

Alves, Ada M. B.; Ángel, Rosa M. del

doi:10.1007/978-3-319-54567-7_8

Cited by 3 publications

(9 citation statements)

References 216 publications

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Section: Resultsmentioning

confidence: 99%

“…The IFPTML-Flavivirus-database consists only of members of the Flavivirus genus; as mentioned in the introduction, the members are closely related to each other and present conserved regions in their genomes . One of the most studied Flaviviruses is the DENV, and its drugs are used as models to treat other members of this species. ,, Therefore, several studies have reported similarities in their compound conditions or characteristics. However, these studies vary in reported activity because of the 10% difference, which makes each of these members unique in their own way. ,, Taking this into consideration, the unique characteristics of these variables should be expanded to make them more specific.…”

Section: Resultsmentioning

confidence: 99%

“…8,9 It has been reported that the proteins encoded by RNA are conserved in members of the Flavivirus genus, for example, DENV serotype 4 shows high similarity to its counterparts in the genus transmitted by mosquitoes. 10,11 Currently, the development of vaccines and drugs against certain members of the Flavivirus genus (YFV, DENV, WNV, Japanese Encephalitis Virus�JEV, etc.) is more widespread than against ZIKV.…”

Section: Introductionmentioning

confidence: 99%

“…Taxonomic analyses have classified DENV, CHIKV, YFV, and ZIKV as members of the Flaviviridae family, Flavivirus genus. − This genus is characterized by a positive-sense RNA of approximately 11 kb. , It has been reported that the proteins encoded by RNA are conserved in members of the Flavivirus genus, for example, DENV serotype 4 shows high similarity to its counterparts in the genus transmitted by mosquitoes. , …”

Section: Introductionmentioning

confidence: 99%

“…Nowadays, the DENV has four different serotypes. In 2016, the ZIKV was classified as a severe disease due to of its effects on newborns. , Most viruses in this family have similar structures; however, there is no specific drug to treat any of them. , Therefore, it is necessary to accelerate the methods of drug discovery and development. The traditional approach involves synthesizing compounds and testing them, which is a trial-and-error process. , The use of chemoinformatic techniques, such as the PTML method, can accelerate the discovery of potential drug candidates that can inhibit the development of this type of virus.…”

Section: Introductionmentioning

confidence: 99%

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Implementation of IFPTML Computational Models in Drug Discovery Against Flaviviridae Family

Velásquez-López,

Ruiz-Escudero,

Arrasate

et al. 2024

J. Chem. Inf. Model.

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The Flaviviridae family consists of single-stranded positive-sense RNA viruses, which contains the genera Flavivirus, Hepacivirus, Pegivirus, and Pestivirus. Currently, there is an outbreak of viral diseases caused by this family affecting millions of people worldwide, leading to significant morbidity and mortality rates. Advances in computational chemistry have greatly facilitated the discovery of novel drugs and treatments for diseases associated with this family. Chemoinformatic techniques, such as the perturbation theory machine learning method, have played a crucial role in developing new approaches based on ML models that can effectively aid drug discovery. The IFPTML models have shown its capability to handle, classify, and process large data sets with high specificity. The results obtained from different models indicates that this methodology is proficient in processing the data, resulting in a reduction of the false positive rate by 4.25%, along with an accuracy of 83% and reliability of 92%. These values suggest that the model can serve as a computational tool in assisting drug discovery efforts and the development of new treatments against Flaviviridae family diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Implementation of IFPTML Computational Models in Drug Discovery Against Flaviviridae Family

Velásquez-López,

Ruiz-Escudero,

Arrasate

et al. 2024

J. Chem. Inf. Model.

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T Cell Responses Induced by DNA Vaccines Based on the DENV2 E and NS1 Proteins in Mice: Importance in Protection and Immunodominant Epitope Identification

et al. 2019

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The importance of the cellular immune response against DENV has been increasingly highlighted in the past few years, in particular for vaccine development. We have previously constructed two plasmids, pE1D2, and pcTPANS1, encoding the envelope (E) ectodomain (domains I, II, and III) and the non-structural 1 (NS1) protein of dengue virus serotype 2 (DENV2), respectively. In the present work, we analyzed the induction of the cellular response in mice immunized with these DNA vaccines and identified the immunogenic peptides. Vaccinated BALB/c mice became protected against a lethal challenge of DENV2. Depletion of CD4 + cells in vaccinated animals almost completely abolished protection elicited by both vaccines. In contrast, a significant number of pE1D2- and pcTPANS1-immunized mice survived virus challenge after depletion of CD8 + cells, although some animals presented morbidity. To identify immunogenic peptides recognized by T cells, we stimulated splenocytes with overlapping peptide libraries covering the E and NS1 proteins and evaluated the production of IFN-γ by ELISPOT. We detected two and three immunodominant epitopes in the E and NS1 proteins, respectively, and four additional NS1-derived peptides after virus challenge. Characterization by intracellular cytokine staining (ICS) revealed that both CD4 + and CD8 + T cells were involved in IFN-γ and TNF-α production. The IFN-γ ICS confirmed reaction of almost all E-derived peptides before challenge and identified other epitopes after infection. All NS1-derived peptides were able to elicit IFN-γ production in CD4 + cells, while only a few peptides induced expression of this cytokine in CD8 + T lymphocytes. Interestingly, we observed an increase in the frequency of either CD4 + or CD8 + T cells producing TNF-α after immunization with the pE1D2 and challenge with DENV2, while lymphocytes from pcTPANS1-vaccinated animals maintained ordinary TNF-α production after virus infection. We also assessed the recognition of E and NS1 immunogenic peptides in C57BL/6 mice due to the difference in MHC haplotype expression. Two NS1-derived epitopes featured prominently in the IFN-γ response with cells from both animal strains. Overall, our results emphasize the importance of the T cell response involved in protection against dengue induced by E and NS1 based DNA vaccines.

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The Innate Immune Response in DENV- and CHIKV-Infected Placentas and the Consequences for the Fetuses: A Minireview

de Andrade Vieira Alves,

Nunes,

Arruda

et al. 2023

Viruses

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Dengue virus (DENV) and chikungunya (CHIKV) are arthropod-borne viruses belonging to the Flaviviridae and Togaviridae families, respectively. Infection by both viruses can lead to a mild indistinct fever or even lead to more severe forms of the diseases, which are characterized by a generalized inflammatory state and multiorgan involvement. Infected mothers are considered a high-risk group due to their immunosuppressed state and the possibility of vertical transmission. Thereby, infection by arboviruses during pregnancy portrays a major public health concern, especially in countries where epidemics of both diseases are regular and public health policies are left aside. Placental involvement during both infections has been already described and the presence of either DENV or CHIKV has been observed in constituent cells of the placenta. In spite of that, there is little knowledge regarding the intrinsic earlier immunological mechanisms that are developed by placental cells in response to infection by both arboviruses. Here, we approach some of the current information available in the literature about the exacerbated presence of cells involved in the innate immune defense of the placenta during DENV and CHIKV infections.

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Dengue Virus and Other Flaviviruses (Zika): Biology, Pathogenesis, Epidemiology, and Vaccine Development

Cited by 3 publications

References 216 publications

Implementation of IFPTML Computational Models in Drug Discovery Against Flaviviridae Family

Implementation of IFPTML Computational Models in Drug Discovery Against Flaviviridae Family

T Cell Responses Induced by DNA Vaccines Based on the DENV2 E and NS1 Proteins in Mice: Importance in Protection and Immunodominant Epitope Identification

The Innate Immune Response in DENV- and CHIKV-Infected Placentas and the Consequences for the Fetuses: A Minireview

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