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Boosting Flavivirus Research: A Pandengue Net Initiative

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 53486

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Special Issue Editors

Dr. Carlos A. Sariol

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Guest Editor

Unit of Comparative Medicine, Caribbean Primate Research Center, Department of Microbiology and Medical Zoology, Department of Internal Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico
Interests: basic research on flavivirus interactions at molecular level and pathogenesis; vaccine development and characterization of novel viruses in non human primate model; also interested and actively involved in clinical trials for several diseases including flavivirus vaccines
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Dr. Mariana Leguia

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Director, Genomics Laboratory, Pontificia Universidad Católica del Perú, Lima, Peru
Interests: study of tropical and neglected infectious diseases using state-of-the-art genomic tools, including ribosome profiling. Particular focus on pathogen discovery and characterization, host-pathogen interactions and changes in gene expression, and evaluation of vaccine efficacy using systems biology approaches
Special Issues, Collections and Topics in MDPI journals

Dr. Daniela Weiskopf

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Guest Editor

Division of Vaccine Discovery La Jolla Institute for Immunology, San Diego, CA, USA
Interests: vaccine discovery; dengue virus; endemic dengue infection; vaccination

Special Issue Information

Dear Colleagues,

The editorial team of the journal Viruses would like to announce the forthcoming Special Issue entitled: "Boosting Flavivirus Research: A Pandengue Net initiative" guest-edited by Dr. Carlos A. Sariol (University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico, USA), Dr. Mariana Leguia (Pontificia Universidad Católica del Perú) and Dr. Daniela Weiskopf (La Jolla Institute for Immunology, Division of Vaccine Discovery).

Since the World Health Organization declared COVID-19 as a pandemic in 2020, of the activities of many researchers (virologists, immunologists, epidemiologists, molecular biologists, among others) have been directed towards this disease. As a consequence, most of the active research in different fields, including flaviviruses research, was put on a “technical hold”. This Special Issue is being put out in collaboration with the Pan-American Dengue Research Network and aims to “boost” the flavivirus research field by offering a dynamic and rapid platform to publish ongoing research work in the field.

DENVs are considered the most important emerging human arboviruses, with worldwide distribution in the tropics, causing an estimated 100–400 million infections each year, 750,000 cases of severe dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), and up to 75,000 deaths every year. According to the WHO, severe dengue is a leading cause of serious illness and death among children in some Asian and Latin American countries, and recently for the USA where after an absence of 65 years DENV has re-established an autochthonous transmission cycle in Florida. The field of dengue research has shown considerable expansion in the last decade, with a licensed vaccine in the market and a number of new vaccine candidates; a better understanding of disease determinants; and new developments in diagnosis, prognosis and investigational treatments. However, there is currently no specific treatment and new effective vaccines are urgently needed. Additionally, for this Special Issue, the scientific scope will be expanded to cover Zika, chikungunya and Mayaro, arboviruses that have recently re-emerged in the Americas with devastating effects for human public health.

In addition, despite of many years of research, there are still multiple open key questions related to complex immune interaction among flaviviruses, including the humoral, T cells and innate immune response. Without doubt those areas need to be explored in order to design effective therapeutics and vaccine approaches.

The Pan-American Dengue Research Network (http://www.pandenguenet.org) is an initiative to gather researchers across the Americas every two years to discuss their recent advancements in the field, communicate this information to the scientific community in the region, foster collaborations among groups, and discuss future research strategies that will further strengthen the field. During these meetings, cutting-edge topics on dengue are presented and discussed. Additionally, for this meeting the scientific scope will be expanded to cover Zika, chikungunya and Mayaro. The collection of reviews and original research papers in this Special Issue is intended to summarize and showcase current research on arboviruses by investigators from the Americas and around the world.

Dr. Carlos A. Sariol
Dr. Mariana Leguia
Dr. Daniela Weiskopf
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Zika
chikungunya
Mayaro
arboviruses
Americas

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Research

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15 pages, 1840 KiB

Open AccessArticle

Dissemination of the Flavivirus Subgenomic Replicon Genome and Viral Proteins by Extracellular Vesicles

by Tomohiro Ishikawa, Kentaro Narita, Kinichi Matsuyama and Michiaki Masuda

Viruses 2024, 16(4), 524; https://doi.org/10.3390/v16040524 - 28 Mar 2024

Viewed by 5772

Abstract

Extracellular vesicles (EVs) such as exosomes have been shown to play physiological roles in cell-to-cell communication by delivering various proteins and nucleic acids. In addition, several studies revealed that the EVs derived from the cells that are infected with certain viruses could transfer the full-length viral genomes, resulting in EVs-mediated virus propagation. However, the possibility cannot be excluded that the prepared EVs were contaminated with infectious viral particles. In this study, the cells that harbor subgenomic replicon derived from the Japanese encephalitis virus and dengue virus without producing any replication-competent viruses were employed as the EV donor. It was demonstrated that the EVs in the culture supernatants of those cells were able to transfer the replicon genome to other cells of various types. It was also shown that the EVs were incorporated by the recipient cells primarily through macropinocytosis after interaction with CD33 and Tim-1/Tim-4 on HeLa and K562 cells, respectively. Since the methods used in this study are free from contamination with infectious viral particles, it is unequivocally indicated that the flavivirus genome can be transferred by EVs from cell to cell, suggesting that this pathway, in addition to the classical receptor-mediated infection, may play some roles in the viral propagation and pathogenesis. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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14 pages, 3065 KiB

Open AccessArticle

Characterization of Dengue Virus 4 Cases in Paraguay, 2019–2020

by Alejandra Rojas, John Shen, Fátima Cardozo, Cynthia Bernal, Oliver Caballero, Sara Ping, Autum Key, Ali Haider, Yvalena de Guillén, Patricia Langjahr, Maria Eugenia Acosta, Laura Aria, Laura Mendoza, Malvina Páez, Marta Von-Horoch, Patricia Luraschi, Sandra Cabral, María Cecilia Sánchez, Aurelia Torres, Benjamin A. Pinsky, Anne Piantadosi and Jesse J. Waggoner Show full author list Hide full author list

Viruses 2024, 16(2), 181; https://doi.org/10.3390/v16020181 - 25 Jan 2024

Viewed by 2035

Abstract

In 2019–2020, dengue virus (DENV) type 4 emerged to cause the largest DENV outbreak in Paraguay’s history. This study sought to characterize dengue relative to other acute illness cases and use phylogenetic analysis to understand the outbreak’s origin. Individuals with an acute illness (≤7 days) were enrolled and tested for DENV nonstructural protein 1 (NS1) and viral RNA by real-time RT-PCR. Near-complete genome sequences were obtained from 62 DENV-4 positive samples. From January 2019 to March 2020, 799 participants were enrolled: 253 dengue (14 severe dengue, 5.5%) and 546 other acute illness cases. DENV-4 was detected in 238 dengue cases (94.1%). NS1 detection by rapid test was 52.5% sensitive (53/101) and 96.5% specific (387/401) for dengue compared to rRT-PCR. DENV-4 sequences were grouped into two clades within genotype II. No clustering was observed based on dengue severity, location, or date. Sequences obtained here were most closely related to 2018 DENV-4 sequences from Paraguay, followed by a 2013 sequence from southern Brazil. DENV-4 can result in large outbreaks, including severe cases, and is poorly detected with available rapid diagnostics. Outbreak strains seem to have been circulating in Paraguay and Brazil prior to 2018, highlighting the importance of sustained DENV genomic surveillance. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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8 pages, 663 KiB

Open AccessCommunication

YELLOW ALERT: Persistent Yellow Fever Virus Circulation among Non-Human Primates in Urban Areas of Minas Gerais State, Brazil (2021–2023)

by Gabriela F. Garcia-Oliveira, Anna Catarina Dias Soares Guimarães, Gabriel Dias Moreira, Thais Alkifeles Costa, Matheus Soares Arruda, Érica Munhoz de Mello, Marlise Costa Silva, Munique Guimarães de Almeida, Kathryn A. Hanley, Nikos Vasilakis and Betânia Paiva Drumond

Viruses 2024, 16(1), 31; https://doi.org/10.3390/v16010031 - 23 Dec 2023

Cited by 1 | Viewed by 1932 | Correction

Abstract

Yellow fever virus (YFV) is the agent of yellow fever (YF), which affects both humans and non-human primates (NHP). Neotropical NHP are highly susceptible to YFV and considered sentinels for YFV circulation. Brazil faced a significant YF outbreak in 2017–2018, with over 2000 human cases and 2000 epizootics cases, mainly in the State of Minas Gerais, Brazil. This study aimed to investigate whether YFV circulation persisted in NHP after the human outbreak had subsided. To this end, NHP carcass samples collected in Minas Gerais from 2021 to 2023 were screened for YFV. RNA was extracted from tissue fragments and used in RT-qPCR targeting the YFV 5’UTR. Liver and lung samples from 166 animals were tested, and the detection of the β-actin mRNA was used to ensure adequacy of RNA isolation. YFV RNA was detected in the liver of 18 NHP carcasses collected mainly from urban areas in 2021 and 2022. YFV positive NHP were mostly represented by Callithrix, from 5 out of the 12 grouped municipalities (mesoregions) in Minas Gerais state. These findings reveal the continued YFV circulation in NHP in urban areas of Minas Gerais during 2021 and 2022, with the attendant risk of re-establishing the urban YFV cycle. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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21 pages, 5240 KiB

Open AccessArticle

Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial–Mesenchymal-Transition-like Changes in Human Microvascular Endothelial Cells

by Manuela Escudero-Flórez, David Torres-Hoyos, Yaneth Miranda-Brand, Ryan L. Boudreau, Juan Carlos Gallego-Gómez and Miguel Vicente-Manzanares

Viruses 2023, 15(7), 1437; https://doi.org/10.3390/v15071437 - 26 Jun 2023

Cited by 2 | Viewed by 2480 | Correction

Abstract

Dengue virus (DENV) is a pathogenic arbovirus that causes human disease. The most severe stage of the disease (severe dengue) is characterized by vascular leakage, hypovolemic shock, and organ failure. Endothelial dysfunction underlies these phenomena, but the causal mechanisms of endothelial dysfunction are poorly characterized. This study investigated the role of c-ABL kinase in DENV-induced endothelial dysfunction. Silencing c-ABL with artificial miRNA or targeting its catalytic activity with imatinib revealed that c-ABL is required for the early steps of DENV infection. DENV-2 infection and conditioned media from DENV-infected cells increased endothelial expression of c-ABL and CRKII phosphorylation, promoted expression of mesenchymal markers, e.g., vimentin and N-cadherin, and decreased the levels of endothelial-specific proteins, e.g., VE-cadherin and ZO-1. These effects were reverted by silencing or inhibiting c-ABL. As part of the acquisition of a mesenchymal phenotype, DENV infection and treatment with conditioned media from DENV-infected cells increased endothelial cell motility in a c-ABL-dependent manner. In conclusion, DENV infection promotes a c-ABL-dependent endothelial phenotypic change that leads to the loss of intercellular junctions and acquisition of motility. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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21 pages, 5126 KiB

Open AccessArticle

Identification of Key Residues in Dengue Virus NS1 Protein That Are Essential for Its Secretion

by Brandon E. K. Tan, Michael R. Beard and Nicholas S. Eyre

Viruses 2023, 15(5), 1102; https://doi.org/10.3390/v15051102 - 30 Apr 2023

Cited by 4 | Viewed by 4449

Abstract

Dengue virus (DENV) non-structural protein 1 (NS1) is involved in multiple aspects of the DENV lifecycle. Importantly, it is secreted from infected cells as a hexameric lipoparticle that mediates vascular damage that is a hallmark of severe dengue. Although the secretion of NS1 is known to be important in DENV pathogenesis, the exact molecular features of NS1 that are required for its secretion from cells are not fully understood. In this study, we employed random point mutagenesis in the context of an NS1 expression vector encoding a C-terminal HiBiT luminescent peptide tag to identify residues within NS1 that are essential for its secretion. Using this approach, we identified 10 point mutations that corresponded with impaired NS1 secretion, with in silico analyses indicating that the majority of these mutations are located within the β-ladder domain. Additional studies on two of these mutants, V220D and A248V, revealed that they prevented viral RNA replication, while studies using a DENV NS1-NS5 viral polyprotein expression system demonstrated that these mutations resulted in a more reticular NS1 localisation pattern and failure to detect mature NS1 at its predicted molecular weight by Western blotting using a conformation-specific monoclonal antibody. Together, these studies demonstrate that the combination of a luminescent peptide tagged NS1 expression system with random point mutagenesis enables rapid identification of mutations that alter NS1 secretion. Two such mutations identified via this approach revealed residues that are essential for correct NS1 processing or maturation and viral RNA replication. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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17 pages, 3355 KiB

Open AccessArticle

Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus

by Dandan Liu, Tanya P. Ndongwe, Juan Ji, Andrew D. Huber, Eleftherios Michailidis, Charles M. Rice, Robert Ralston, Philip R. Tedbury and Stefan G. Sarafianos

Viruses 2023, 15(4), 981; https://doi.org/10.3390/v15040981 - 17 Apr 2023

Cited by 1 | Viewed by 3162

Abstract

Several direct-acting antivirals (DAAs) are available, providing interferon-free strategies for a hepatitis C cure. In contrast to DAAs, host-targeting agents (HTAs) interfere with host cellular factors that are essential in the viral replication cycle; as host genes, they are less likely to rapidly mutate under drug pressure, thus potentially exhibiting a high barrier to resistance, in addition to distinct mechanisms of action. We compared the effects of cyclosporin A (CsA), a HTA that targets cyclophilin A (CypA), to DAAs, including inhibitors of nonstructural protein 5A (NS5A), NS3/4A, and NS5B, in Huh7.5.1 cells. Our data show that CsA suppressed HCV infection as rapidly as the fastest-acting DAAs. CsA and inhibitors of NS5A and NS3/4A, but not of NS5B, suppressed the production and release of infectious HCV particles. Intriguingly, while CsA rapidly suppressed infectious extracellular virus levels, it had no significant effect on the intracellular infectious virus, suggesting that, unlike the DAAs tested here, it may block a post-assembly step in the viral replication cycle. Hence, our findings shed light on the biological processes involved in HCV replication and the role of CypA. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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10 pages, 420 KiB

Open AccessArticle

Symptomatic Chikungunya Virus Infection and Pregnancy Outcomes: A Nested Case-Control Study in French Guiana

by Célia Basurko, Najeh Hcini, Magalie Demar, Philippe Abboud, the CMFdeng study group, Mathieu Nacher, Gabriel Carles, Véronique Lambert and Séverine Matheus

Viruses 2022, 14(12), 2705; https://doi.org/10.3390/v14122705 - 2 Dec 2022

Cited by 6 | Viewed by 2895

Abstract

During the Chikungunya epidemic in the Caribbean and Latin America, pregnant women were affected by the virus in French Guiana. The question of the impact of the virus on pregnancy was raised because of the lack of scientific consensus and published data in the region. Thus, during the Chikungunya outbreak in French Guiana, a comparative study was set up using a cohort of pregnant women. The objective was to compare pregnancy and neonatal outcomes between pregnant women with Chikungunya virus (CHIKV) infection and pregnant women without CHIKV. Of 653 mothers included in the cohort, 246 mothers were included in the case-control study: 73 had CHIKV fever during pregnancy and 173 had neither fever nor CHIKV during pregnancy. The study did not observe any severe clinical presentation of CHIKV in the participating women. There were no intensive care unit admissions. In addition, the study showed no significant difference between the two groups with regard to pregnancy complications. However, the results showed a potential excess risk of neonatal ICU admission of the newborn when the maternal infection occurred within 7 days before delivery. These results suggest that special attention should be paid to neonates whose mothers were infected with CHIKV shortly before delivery. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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Review

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22 pages, 1752 KiB

Open AccessReview

Arboviral Risk Associated with Solid Organ and Hematopoietic Stem Cell Grafts: The Prophylactic Answers Proposed by the French High Council of Public Health in a National Context

by Bruno Pozzetto, Gilda Grard, Guillaume Durand, Marie-Claire Paty, Pierre Gallian, Sophie Lucas-Samuel, Stéphanie Diéterlé, Muriel Fromage, Marc Durand, Didier Lepelletier, Christian Chidiac, Bruno Hoen and Xavier Nicolas de Lamballerie

Viruses 2023, 15(9), 1783; https://doi.org/10.3390/v15091783 - 22 Aug 2023

Cited by 2 | Viewed by 1812

Abstract

Diseases caused by arboviruses are on the increase worldwide. In addition to arthropod bites, most arboviruses can be transmitted via accessory routes. Products of human origin (labile blood products, solid organs, hematopoietic stem cells, tissues) present a risk of contamination for the recipient if the donation is made when the donor is viremic. Mainland France and its overseas territories are exposed to a complex array of imported and endemic arboviruses, which differ according to their respective location. This narrative review describes the risks of acquiring certain arboviral diseases from human products, mainly solid organs and hematopoietic stem cells, in the French context. The main risks considered in this study are infections by West Nile virus, dengue virus, and tick-borne encephalitis virus. The ancillary risks represented by Usutu virus infection, chikungunya, and Zika are also addressed more briefly. For each disease, the guidelines issued by the French High Council of Public Health, which is responsible for mitigating the risks associated with products of human origin and for supporting public health policy decisions, are briefly outlined. This review highlights the need for a “One Health” approach and to standardize recommendations at the international level in areas with the same viral epidemiology. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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13 pages, 534 KiB

Open AccessReview

The Role of NS1 Protein in the Diagnosis of Flavivirus Infections

by Ron Fisher, Yaniv Lustig, Ella H. Sklan and Eli Schwartz

Viruses 2023, 15(2), 572; https://doi.org/10.3390/v15020572 - 19 Feb 2023

Cited by 11 | Viewed by 4642

Abstract

Nonstructural protein 1 (NS1) is a glycoprotein among the flavivirus genus. It is found in both membrane-associated and soluble secreted forms, has an essential role in viral replication, and modulates the host immune response. NS1 is secreted from infected cells within hours after viral infection, and thus immunodetection of NS1 can be used for early serum diagnosis of dengue fever infections instead of real-time (RT)-PCR. This method is fast, simple, and affordable, and its availability could provide an easy point-of-care testing solution for developing countries. Early studies show that detecting NS1 in cerebrospinal fluid (CSF) samples is possible and can improve the surveillance of patients with dengue-associated neurological diseases. NS1 can be detected postmortem in tissue specimens. It can also be identified using noninvasive methods in urine, saliva, and dried blood spots, extending the availability and effective detection period. Recently, an enzyme-linked immunosorbent assay (ELISA) assay for detecting antibodies directed against Zika virus NS1 has been developed and used for diagnosing Zika infection. This NS1-based assay was significantly more specific than envelope protein-based assays, suggesting that similar assays might be more specific for other flaviviruses as well. This review summarizes the knowledge on flaviviruses’ NS1′s potential role in antigen and antibody diagnosis. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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14 pages, 794 KiB

Open AccessReview

Targeting Aedes aegypti Metabolism with Next-Generation Insecticides

by Michael J. Conway, Douglas P. Haslitt and Benjamin M. Swarts

Viruses 2023, 15(2), 469; https://doi.org/10.3390/v15020469 - 8 Feb 2023

Cited by 6 | Viewed by 3705

Abstract

Aedes aegypti is the primary vector of dengue virus (DENV), zika virus (ZIKV), and other emerging infectious diseases of concern. A key disease mitigation strategy is vector control, which relies heavily on the use of insecticides. The development of insecticide resistance poses a major threat to public health worldwide. Unfortunately, there is a limited number of chemical compounds available for vector control, and these chemicals can have off-target effects that harm invertebrate and vertebrate species. Fundamental basic science research is needed to identify novel molecular targets that can be exploited for vector control. Next-generation insecticides will have unique mechanisms of action that can be used in combination to limit selection of insecticide resistance. Further, molecular targets will be species-specific and limit off-target effects. Studies have shown that mosquitoes rely on key nutrients during multiple life cycle stages. Targeting metabolic pathways is a promising direction that can deprive mosquitoes of nutrition and interfere with development. Metabolic pathways are also important for the virus life cycle. Here, we review studies that reveal the importance of dietary and stored nutrients during mosquito development and infection and suggest strategies to identify next-generation insecticides with a focus on trehalase inhibitors. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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19 pages, 18941 KiB

Open AccessReview

Immune-Mediated Pathogenesis in Dengue Virus Infection

by Arshi Khanam, Hector Gutiérrez-Barbosa, Kirsten E. Lyke and Joel V. Chua

Viruses 2022, 14(11), 2575; https://doi.org/10.3390/v14112575 - 21 Nov 2022

Cited by 26 | Viewed by 11215

Abstract

Dengue virus (DENV) infection is one of the major public health concerns around the globe, especially in the tropical regions of the world that contribute to 75% percent of dengue cases. While the majority of DENV infections are mild or asymptomatic, approximately 5% of the cases develop a severe form of the disease that is mainly attributed to sequential infection with different DENV serotypes. The severity of dengue depends on many immunopathogenic mechanisms involving both viral and host factors. Emerging evidence implicates an impaired immune response as contributing to disease progression and severity by restricting viral clearance and inducing severe inflammation, subsequently leading to dengue hemorrhagic fever and dengue shock syndrome. Moreover, the ability of DENV to infect a wide variety of immune cells, including monocytes, macrophages, dendritic cells, mast cells, and T and B cells, further dysregulates the antiviral functions of these cells, resulting in viral dissemination. Although several risk factors associated with disease progression have been proposed, gaps persist in the understanding of the disease pathogenesis and further investigations are warranted. In this review, we discuss known mechanisms of DENV-mediated immunopathogenesis and its association with disease progression and severity. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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22 pages, 2034 KiB

Open AccessReview

Endothelial Dysfunction, HMGB1, and Dengue: An Enigma to Solve

by María-Angélica Calderón-Peláez, Carolina Coronel-Ruiz, Jaime E. Castellanos and Myriam L. Velandia-Romero

Viruses 2022, 14(8), 1765; https://doi.org/10.3390/v14081765 - 12 Aug 2022

Cited by 6 | Viewed by 3999

Abstract

Dengue is a viral infection caused by dengue virus (DENV), which has a significant impact on public health worldwide. Although most infections are asymptomatic, a series of severe clinical manifestations such as hemorrhage and plasma leakage can occur during the severe presentation of the disease. This suggests that the virus or host immune response may affect the protective function of endothelial barriers, ultimately being considered the most relevant event in severe and fatal dengue pathogenesis. The mechanisms that induce these alterations are diverse. It has been suggested that the high mobility group box 1 protein (HMGB1) may be involved in endothelial dysfunction. This non-histone nuclear protein has different immunomodulatory activities and belongs to the alarmin group. High concentrations of HMGB1 have been detected in patients with several infectious diseases, including dengue, and it could be considered as a biomarker for the early diagnosis of dengue and a predictor of complications of the disease. This review summarizes the main features of dengue infection and describes the known causes associated with endothelial dysfunction, highlighting the involvement and possible relationship between HMGB1 and DENV. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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Other

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2 pages, 190 KiB

Open AccessCorrection

Correction: Escudero-Flórez et al. Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial–Mesenchymal-Transition-like Changes in Human Microvascular Endothelial Cells. Viruses 2023, 15, 1437

by Manuela Escudero-Flórez, David Torres-Hoyos, Yaneth Miranda-Brand, Ryan L. Boudreau, Juan Carlos Gallego-Gómez and Miguel Vicente-Manzanares

Viruses 2023, 15(11), 2252; https://doi.org/10.3390/v15112252 - 13 Nov 2023

Viewed by 907

Abstract

Ryan L [...] Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

9 pages, 1347 KiB

Open AccessBrief Report

Construction and Rescue of a DNA-Launched DENV2 Infectious Clone

by Madeline Holliday, Lochlain Corliss and Nicholas J. Lennemann

Viruses 2023, 15(2), 275; https://doi.org/10.3390/v15020275 - 18 Jan 2023

Cited by 1 | Viewed by 2347

Abstract

Flaviviruses represent a large group of globally significant, insect-borne pathogens. For many of these viruses, there is a lack of antivirals and vaccines. Thus, there is a need to continue the development of tools to further advance our efforts to combat these pathogens, including reverse genetics techniques. Traditionally, reverse genetics methods for flaviviruses rely on producing infectious RNA from in vitro transcription reactions followed by electroporation or transfection into permissive cell lines. However, the production of Zika virus has been successful from CMV promoter-driven expression plasmids, which provides cost and time advantages. In this report, we describe the design and construction of a DNA-launched infectious clone for dengue virus (DENV) serotype 2 strain 16681. An artificial intron was introduced in the nonstructural protein 1 segment of the viral genome to promote stability in bacteria. We found that rescued viruses maintained the ability to form plaques and replicate efficiently in commonly used cell lines. Thus, we present a rapid and cost-effective method for producing DENV2 strain 16681 from plasmid DNA. This construct will be a useful platform for the continued development of anti-DENV therapeutics and vaccines. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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