scholarly journals Epidemiological implications of the genetic diversification of dengue virus (DENV) serotypes and genotypes in Mexico

2020 ◽  
Vol 84 ◽  
pp. 104391 ◽  
Author(s):  
Ericel Hernández-García ◽  
Maria de Lourdes Muñoz ◽  
Randy E. David ◽  
Gerardo Pérez-Ramírez ◽  
Joel Navarrete-Espinosa ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Denv Serotypes

scholarly journals Development of Bacteriophage Virus-Like Particle Vaccines Displaying Conserved Epitopes of Dengue Virus Non-Structural Protein 1

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 726
Author(s):  
Nikole L. Warner ◽  
Kathryn M. Frietze
Keyword(s):  
Dengue Virus ◽  
Population Based ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Denv Serotypes ◽  
Conserved Regions ◽  
Virus Like Particle ◽  
Dependent Cell ◽  
Infected Cells ◽  
Plasma Leakage

Dengue virus (DENV) is a major global health problem, with over half of the world’s population at risk of infection. Despite over 60 years of efforts, no licensed vaccine suitable for population-based immunization against DENV is available. Here, we describe efforts to engineer epitope-based vaccines against DENV non-structural protein 1 (NS1). NS1 is present in DENV-infected cells as well as secreted into the blood of infected individuals. NS1 causes disruption of endothelial cell barriers, resulting in plasma leakage and hemorrhage. Immunizing against NS1 could elicit antibodies that block NS1 function and also target NS1-infected cells for antibody-dependent cell cytotoxicity. We identified highly conserved regions of NS1 from all four DENV serotypes. We generated synthetic peptides to these regions and chemically conjugated them to bacteriophage Qβ virus-like particles (VLPs). Mice were immunized two times with the candidate vaccines and sera were tested for the presence of antibodies that bound to the cognate peptide, recombinant NS1 from all four DENV serotypes, and DENV-2-infected cells. We found that two of the candidate vaccines elicited antibodies that bound to recombinant NS1, and one candidate vaccine elicited antibodies that bound to DENV-infected cells. These results show that an epitope-specific vaccine against conserved regions of NS1 could be a promising approach for DENV vaccines or therapeutics to bind circulating NS1 protein.

A bioinformatics approach to investigate serum and hematopoietic cell-specific therapeutic microRNAs targeting the 3' UTRs of all four Dengue virus serotypes

2021 ◽  
Author(s):  
Mirza Sarwar Baig ◽  
Anuja Krishnan
Keyword(s):  
Dengue Virus ◽  
Antigen Processing ◽  
Target Genes ◽  
Public Health Problem ◽  
Hematopoietic Cell ◽  
Viral Gene ◽  
P Value ◽  
Pathway Enrichment Analysis ◽  
Global Public Health ◽  
Denv Serotypes

Abstract Hyperendemic circulation of all four Dengue virus (DENV) serotypes is a severe global public health problem, so any vaccine or therapeutics should be able to target all four of them. Cells of hemopoietic origin are believed to be primary sites of DENV replication. This study aimed to identify potential host miRNAs that target 3' UTR of all 4 DENV serotypes, thereby directly regulating viral gene expression or indirectly modulating the host system at different virus infection steps. We used four prediction algorithms viz. miRanda, RNA22, RNAhybrid, and StarMir for predicting miRNA, targeting 3'UTR of all four DENV serotypes. Statistically, the most significant miRNA targets were screened based on their Log10 P-value (> 0.0001) of GO term and KEGG pathway enrichment analysis. The intersection test of at least three prediction tools identified a total of 30 miRNAs, which could bind to 3'UTR of all four DENV serotypes. Of the 30, eight miRNAs were of hematopoietic cell origin. GO term enrichment and KEGG analysis showed four hemopoietic origin miRNAs target genes of the biological processes mainly involved in the innate immune response, mRNA 3'-end processing, antigen processing, and presentation and nuclear-transcribed mRNA catabolic process.

scholarly journals Use of immunodot blot and multiplex reverse transcriptase-polymerase chain reaction in dengue virus detection in macerates of Aedes aegypti larvae

2012 ◽  
Vol 3 (1) ◽  
pp. 13
Author(s):  
Aline T.A. Chagas ◽  
Michelle D. Oliveira ◽  
Jose M.S. Mezencio ◽  
Eduardo A.M. Silva ◽  
Leandro L. Oliveira ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Reverse Transcriptase ◽  
Epidemiological Surveillance ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Denv Serotypes ◽  
Polymerase Chain ◽  
Pcr Techniques

The <em>Dengue virus</em> is the main arbovirus that affects man in terms of morbidity and mortality. The detection of the virus is very important for epidemiological surveillance, so here we propose to standardize and compare the immunodot blot (IDB) and multiplex reverse transcriptase-polymerase chain reaction (M-RT-PCR) techniques to detect and characterize the dengue virus (DENV) serotypes in samples of <em>Aedes aegypti</em> larvae. Thus, the IDB and M-RT-PCR techniques were standardized using macerated samples of larvae collected in nature. The use of monoclonal antibodies in IDB has not shown great results, but DENV detection through this method was possible using polyclonal antibodies. The distinction of serotypes 1, 2 and 3 was carried out by M-RT-PCR.

scholarly journals Boosting can explain patterns of fluctuations of ratios of inapparent to symptomatic dengue virus infections

2021 ◽  
Vol 118 (14) ◽  
pp. e2013941118
Author(s):  
Laura W. Alexander ◽  
Rotem Ben-Shachar ◽  
Leah C. Katzelnick ◽  
Guillermina Kuan ◽  
Angel Balmaseda ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Denv Infection ◽  
Protective Effects ◽  
Virus Infections ◽  
Denv Serotypes ◽  
Symptomatic Disease ◽  
Large Fluctuations ◽  
Antibody Titers ◽  
Dengue Control ◽  
Arboviral Disease

Dengue is the most prevalent arboviral disease worldwide, and the four dengue virus (DENV) serotypes circulate endemically in many tropical and subtropical regions. Numerous studies have shown that the majority of DENV infections are inapparent, and that the ratio of inapparent to symptomatic infections (I/S) fluctuates substantially year-to-year. For example, in the ongoing Pediatric Dengue Cohort Study (PDCS) in Nicaragua, which was established in 2004, the I/S ratio has varied from 16.5:1 in 2006–2007 to 1.2:1 in 2009–2010. However, the mechanisms explaining these large fluctuations are not well understood. We hypothesized that in dengue-endemic areas, frequent boosting (i.e., exposures to DENV that do not lead to extensive viremia and result in a less than fourfold rise in antibody titers) of the immune response can be protective against symptomatic disease, and this can explain fluctuating I/S ratios. We formulate mechanistic epidemiologic models to examine the epidemiologic effects of protective homologous and heterologous boosting of the antibody response in preventing subsequent symptomatic DENV infection. We show that models that include frequent boosts that protect against symptomatic disease can recover the fluctuations in the I/S ratio that we observe, whereas a classic model without boosting cannot. Furthermore, we show that a boosting model can recover the inverse relationship between the number of symptomatic cases and the I/S ratio observed in the PDCS. These results highlight the importance of robust dengue control efforts, as intermediate dengue control may have the potential to decrease the protective effects of boosting.

scholarly journals Doratoxylon apetalum, an Indigenous Medicinal Plant from Mascarene Islands, Is a Potent Inhibitor of Zika and Dengue Virus Infection in Human Cells

2019 ◽  
Vol 20 (10) ◽  
pp. 2382 ◽  
Author(s):  
Juliano G. Haddad ◽  
Andrea Cristine Koishi ◽  
Arnaud Gaudry ◽  
Claudia Nunes Duarte dos Santos ◽  
Wildriss Viranaicken ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Medicinal Plant ◽  
Dengue Virus ◽  
Denv Infection ◽  
Antiviral Drugs ◽  
Human Cells ◽  
Host Cells ◽  
Global Public Health ◽  
Denv Serotypes ◽  
Mascarene Islands

Zika virus (ZIKV) and Dengue virus (DENV) are mosquito-borne viruses of the Flavivirus genus that could cause congenital microcephaly and hemorrhage, respectively, in humans, and thus present a risk to global public health. A preventive vaccine against ZIKV remains unavailable, and no specific antiviral drugs against ZIKV and DENV are licensed. Medicinal plants may be a source of natural antiviral drugs which mostly target viral entry. In this study, we evaluate the antiviral activity of Doratoxylum apetalum, an indigenous medicinal plant from the Mascarene Islands, against ZIKV and DENV infection. Our data indicated that D. apetalum exhibited potent antiviral activity against a contemporary epidemic strain of ZIKV and clinical isolates of four DENV serotypes at non-cytotoxic concentrations in human cells. Time-of-drug-addition assays revealed that D. apetalum extract acts on ZIKV entry by preventing the internalisation of virus particles into the host cells. Our data suggest that D. apetalum-mediated ZIKV inhibition relates to virus particle inactivation. We suggest that D. apetalum could be a promising natural source for the development of potential antivirals against medically important flaviviruses.

scholarly journals Low seroprevalence of Zika virus infection among adults in Southern Taiwan

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu-Wen Chien ◽  
Tzu-Chuan Ho ◽  
Pei-Wen Huang ◽  
Nai-Ying Ko ◽  
Wen-Chien Ko ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Migrant Workers ◽  
Zika Virus ◽  
Southeast Asian ◽  
Asian Countries ◽  
Zikv Infection ◽  
Serological Tests ◽  
Cross Sectional ◽  
Denv Serotypes ◽  
Southeast Asian Countries

Abstract Background We recently conducted a serosurvey of newly arrived workers in Taiwan from four Southeast Asian countries which revealed that 1% of the migrant workers had laboratory-confirmed recent Zika virus (ZIKV) infection. Taiwan, where Aedes mosquitoes are prevalent, has a close relationship with Southeast Asian countries. Up to now, 21 imported cases of ZIKV infection have been reported in Taiwan, but there has been no confirmed indigenous case. The aim of this serosurvey was to assess whether there was unrecognized ZIKV infections in Taiwan. Methods A total of 212 serum samples collected in a cross-sectional seroepidemiologic study conducted during the end of the 2015 dengue epidemic in Tainan, Taiwan, were analyzed. Anti-ZIKV IgM and IgG were tested using commercial enzyme-linked immunosorbent assays (ELISAs). Plaque reduction neutralization tests (PRNTs) for ZIKV and four dengue virus (DENV) serotypes were performed for samples with positive anti-ZIKV antibodies. A confirmed case of ZIKV infection was defined by ZIKV PRNT90 titer ratio ≥ 4 compared to four DENV serotypes. Results The mean age of the 212 participants was 54.0 years (standard deviation 13.7 years), and female was predominant (67.0%). Anti-ZIKV IgM and IgG were detected in 0 (0%) and 9 (4.2%) of the 212 participants, respectively. For the 9 samples with anti-ZIKV IgG, only 1 sample had 4 times higher ZIKV PRNT90 titers compared to PRNT90 titers against four dengue virus serotypes; this individual denied having traveled abroad. Conclusions The results suggest that undetected indigenous ZIKV transmission might have occurred in Taiwan. The findings also suggest that the threat of epidemic transmission of ZIKV in Taiwan does exist due to extremely low-level of herd immunity. Our study also indicates that serological tests for ZIKV-specific IgG remain a big challenge due to cross-reactivity, even in dengue non-endemic countries.

scholarly journals Dengue Virus and the Relationship with MicroRNAs

2020 ◽  
Author(s):  
Samir Casseb ◽  
Karla de Melo
Keyword(s):  
Dengue Virus ◽  
Viral Infection ◽  
Viral Infections ◽  
Immune Defense ◽  
Tropical Regions ◽  
Denv Serotypes ◽  
History Of ◽  
Infection Processes ◽  
The Relationship

Dengue is an acute febrile disease caused by a virus of the genus Flavivirus, family Flaviviridae, endemic in tropical regions of the globe. The agent is a virus with single-stranded RNA, classified into four distinct dengue virus (DENV) serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The host’s innate and adaptive immune responses play an essential role in determining the natural history of viral infections, especially in dengue. In this context, it has observed in recent years that the presence of RNA interference (RNAi) in viral infection processes is increasing, as well as immune defense. The context microRNAs (miRNAs) go for stood out, as their presence during viral infection, both in the replication of the virus and in the defense against these infections, becomes increasingly noticeable, therefore, making it increasingly necessary to better understand the role of these small RNAs within viral infection by DENV and what their consequences are in aggravating the consequences of patients affected by this disease.

scholarly journals CD8+T Cells Can Mediate Short-Term Protection against Heterotypic Dengue Virus Reinfection in Mice

2015 ◽  
Vol 89 (12) ◽  
pp. 6494-6505 ◽  
Author(s):  
Raphaël M. Zellweger ◽  
William W. Tang ◽  
William E. Eddy ◽  
Kevin King ◽  
Marisa C. Sanchez ◽  
...  
Keyword(s):  
T Cells ◽  
Dengue Virus ◽  
Cellular Immunity ◽  
Vaccine Design ◽  
Neutralizing Antibody ◽  
Cross Protection ◽  
Denv Serotypes ◽  
Transient Period ◽  
Protection Period

ABSTRACTDengue virus (DENV) is a major public health threat worldwide. Infection with one of the four serotypes of DENV results in a transient period of protection against reinfection with all serotypes (cross-protection), followed by lifelong immunity to the infecting serotype. While a protective role for neutralizing antibody responses is well established, the contribution of T cells to reinfection is less clear, especially during heterotypic reinfection. This study investigates the role of T cells during homotypic and heterotypic DENV reinfection. Mice were sequentially infected with homotypic or heterotypic DENV serotypes, and T cell subsets were depleted before the second infection to assess the role of DENV-primed T cells during reinfection. Mice primed nonlethally with DENV were protected against reinfection with either a homotypic or heterotypic serotype 2 weeks later. Homotypic priming induced a robust neutralizing antibody response, whereas heterotypic priming elicited binding, but nonneutralizing antibodies. CD8+T cells were required for protection against heterotypic, but not homotypic, reinfection. These results suggest that T cells can contribute crucially to protection against heterotypic reinfection in situations where humoral responses alone may not be protective. Our findings have important implications for vaccine design, as they suggest that inducing both humoral and cellular responses during vaccination may maximize protective efficacy across all DENV serotypes.IMPORTANCEDengue virus is present in more than 120 countries in tropical and subtropical regions. Infection with dengue virus can be asymptomatic, but it can also progress into the potentially lethal severe dengue disease. There are four closely related dengue virus serotypes. Infection with one serotype results in a transient period of resistance against all serotypes (cross-protection), followed by lifelong resistance to the infecting serotype, but not the other ones. The duration and mechanisms of the transient cross-protection period remain elusive. This study investigates the contribution of cellular immunity to cross-protection using mouse models of DENV infection. Our results demonstrate that cellular immunity is crucial to mediate cross-protection against reinfection with a different serotype, but not for protection against reinfection with the same serotype. A better understanding of the mediators responsible for the cross-protection period is important for vaccine design, as an ideal vaccine against dengue virus should efficiently protect against all serotypes.

scholarly journals Differential replication of dengue virus serotypes 2 and 3 in coinfections of C6/36 cells and Aedes aegypti mosquitoes

2014 ◽  
Vol 8 (07) ◽  
pp. 876-884 ◽  
Author(s):  
Diana Carolina Quintero-Gil ◽  
Marta Ospina ◽  
Jorge Emilio Osorio-Benitez ◽  
Marlen Martinez-Gutierrez
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Cell Viability ◽  
Denv Infection ◽  
Replication Capacity ◽  
Denv Serotypes ◽  
Viral Genomes ◽  
Diphenyltetrazolium Bromide

Introduction: Different dengue virus (DENV) serotypes have been associated with greater epidemic potential. In turn, the increased frequency in cases of severe forms of dengue has been associated with the cocirculation of several serotypes. Because Colombia is a country with an endemic presence of all four DENV serotypes, the aim of this study was to evaluate the in vivo and in vitro replication of the DENV-2 and DENV-3 strains under individual infection and coinfection conditions. Methodology: C6/36HT cells were infected with the two strains individually or simultaneously (coinfection). Replication capacity was evaluated by RT-qPCR, and the effects on cell viability were assessed with an MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Additionally, Aedes aegypti mosquitoes were artificially fed the two strains of each serotype individually or simultaneously. The viral genomes were quantified by RT-qPCR and the survival of the infected mosquitoes was compared to that of uninfected controls. Results: In single infections, three strains significantly affected C6/36HT cell viability, but no significant differences were found in the replication capacities of the strains of the same serotype. In the in vivo infections, mosquito survival was not affected, and no significant differences in replication between strains of the same serotype were found. Finally, in coinfections, serotype 2 replicated with a thousandfold greater efficiency than serotype 3 did both in vitro and in vivo. Conclusions: Due to the cocirculation of serotypes in endemic regions, further studies of coinfections in a natural environment would further an understanding of the transmission dynamics that affect DENV infection epidemiology.

Demonstration of marmosets (Callithrix jacchus) as a non-human primate model for secondary dengue virus infection: high levels of viraemia and serotype cross-reactive antibody responses consistent with secondary infection of humans

2014 ◽  
Vol 95 (3) ◽  
pp. 591-600 ◽  
Author(s):  
Meng Ling Moi ◽  
Tomohiko Takasaki ◽  
Tsutomu Omatsu ◽  
Shinichiro Nakamura ◽  
Yuko Katakai ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Primary Infection ◽  
Secondary Infection ◽  
Denv Infection ◽  
Callithrix Jacchus ◽  
Antibody Responses ◽  
Infection Model ◽  
Primate Model ◽  
Bhk Cells ◽  
Denv Serotypes

There are four dengue virus (DENV) serotypes. Primary infection with one does not confer protective immunity against the others. We have reported previously that the marmoset (Callithrix jacchus) is a useful primary DENV infection model. It has been reported that secondary DENV infection with a heterotypic serotype induces viraemia kinetics and antibody responses that differ from those in primary infection. Thus, it is important to determine the utility of the marmoset as a model for secondary DENV infection. Marmosets were infected with heterologous DENV by secondary inoculation, and viraemia kinetics and antibody responses were analysed. The marmosets consistently developed high levels of viraemia after the secondary inoculation with heterologous DENV serotypes. IgM responses were lower compared with primary inoculation responses, whilst IgG responses were rapid and high. Neutralizing activities, which possessed serotype cross-reactive activities, were detected as early as 4 days after inoculation. In addition, infectious viraemia titres were higher when assayed with Fcγ receptor-expressing baby hamster kidney (BHK) cells than when assayed with conventional BHK cells, suggesting the presence of infectious virus–antibody immune complexes. After secondary infection with heterotypic DENV, the marmosets demonstrated viraemia kinetics, IgM and IgG responses, and high levels of serotype cross-reactive neutralizing antibody responses, all of which were consistent with secondary DENV infection in humans. The results indicate the marmoset as a useful animal for studying secondary, as well as primary, DENV infection.

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