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Frontiers in Public Health 2023Dengue has been endemic in Southeast Asian countries for decades. There are few reports tracing the dynamics of dengue in real time. In this study, we generated hundreds...
OBJECTIVES
Dengue has been endemic in Southeast Asian countries for decades. There are few reports tracing the dynamics of dengue in real time. In this study, we generated hundreds of pathogen genomes to understand the genomic epidemiology of an outbreak in a hyper-endemic area of dengue.
METHODS
We leveraged whole-genome short-read sequencing (PE150) to generate genomes of the dengue virus and investigated the genomic epidemiology of a dengue virus transmission in a mesoscale outbreak in Shantou, China, in 2019.
RESULTS
The outbreak was sustained from July to December 2019. The total accumulated number of laboratory-confirmed cases was 944. No gender bias or fatalities were recorded. Cambodia and Singapore were the main sources of imported dengue cases (74.07%, = 20). A total of 284 dengue virus strains were isolated, including 259 DENV-1, 24 DENV-2, and 1 DENV-3 isolates. We generated the entire genome of 252 DENV isolates (229 DENV-1, 22 DENV-2, and 1 DENV-3), which represented 26.7% of the total cases. Combined epidemiological and phylogenetic analyses indicated multiple independent introductions. The internal transmission evaluations and transmission network reconstruction supported the inference of phylodynamic analysis, with high Bayes factor support in BSSVS analysis. Two expansion founders and transmission chains were detected in CCH and LG of Shantou.
CONCLUSIONS
We observed the instant effects of genomic epidemiology in monitoring the dynamics of DENV and highlighted its prospects for real-time tracing of outbreaks of other novel agents in the future.
Topics: China; Dengue; Humans; Genome, Viral; Dengue Virus; Disease Outbreaks; Phylogeny; Male; Female; Young Adult; Adult; Middle Aged; Infant; Child, Preschool; Child; Adolescent; Aged; Aged, 80 and over
PubMed: 37522010
DOI: 10.3389/fpubh.2023.1035060 -
Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination.Cell Host & Microbe Nov 2023The envelope (E) glycoprotein is the primary target of type-specific (TS) neutralizing antibodies (nAbs) after infection with any of the four distinct dengue virus...
The envelope (E) glycoprotein is the primary target of type-specific (TS) neutralizing antibodies (nAbs) after infection with any of the four distinct dengue virus serotypes (DENV1-4). nAbs can be elicited to distinct structural E domains (EDs) I, II, or III. However, the relative contribution of these domain-specific antibodies is unclear. To identify the primary DENV3 nAb targets in sera after natural infection or vaccination, chimeric DENV1 recombinant encoding DENV3 EDI, EDII, or EDIII were generated. DENV3 EDII is the principal target of TS polyclonal nAb responses and encodes two or more neutralizing epitopes. In contrast, some were individuals vaccinated with a DENV3 monovalent vaccine-elicited serum TS nAbs targeting each ED in a subject-dependent fashion, with an emphasis on EDI and EDIII. Vaccine responses were also sensitive to DENV3 genotypic variation. This DENV1/3 panel allows the measurement of serum ED TS nAbs, revealing differences in TS nAb immunity after natural infection or vaccination.
Topics: Humans; Antibodies, Viral; Dengue Virus; Antibodies, Neutralizing; Dengue Vaccines; Viral Envelope Proteins; Glycoproteins; Vaccination; Dengue
PubMed: 37909048
DOI: 10.1016/j.chom.2023.10.004 -
Cureus Oct 2023Dengue is a very serious public health problem that can manifest a wide range of symptoms from asymptomatic to fatal conditions, such as dengue shock syndrome (DSS). It... (Review)
Review
Dengue is a very serious public health problem that can manifest a wide range of symptoms from asymptomatic to fatal conditions, such as dengue shock syndrome (DSS). It is a life-threatening mosquito-borne viral infection widely spread in tropical areas. Dengue virus transmission occurs from an infected mosquito to humans. Various factors are responsible for the occurrence of the disease, such as viral load, age of the host, immune status of the host, and genetic variability. Dengue infection occurs in three phases: febrile, critical, and recovery. The febrile phase lasts for seven days and manifests symptoms such as high-grade fever, headache, arthralgia, and backache, and in some cases, the upper respiratory tract and gastrointestinal tract are also involved. Severe dengue is characterized by endothelial dysfunction that causes vascular permeability and plasma leakage. The fundamental mechanisms of these immune pathologies are not yet known. Dengue manifests various complications such as dengue encephalopathy, encephalitis, stroke, ocular involvement, acute transverse myelitis, myalgia, and cerebellar syndrome, but the most commonly seen is liver involvement. Dengue is managed supportively because there are no proven curative treatments. The cornerstone of care during the critical period of dengue is prudent fluid resuscitation. The first fluid of preference is a crystalloid. Prophylactic transfusion of platelets is not advised. The occurrence of four antigenically different dengue virus serotypes, each able to elicit a cross-reactive and disease-enhancing antibody response against the other three serotypes, has made the creation of the dengue vaccine a difficult undertaking. The development of a dengue vaccine has faced significant challenges due to a lack of the best animal models and a variety of immunological conditions in people, particularly in endemic locations. Dengvaxia is a live attenuated vaccine, which was developed by Sanofi. It is made up of four chimeric vaccine viruses produced by Vero cells.
PubMed: 38021722
DOI: 10.7759/cureus.46713 -
Travel Medicine and Infectious Disease 2023Dengue is a vector borne disease caused by virus serotypes DENV-1, DENV-2, DENV-3, and DENV-4, representing a significant public health concern in the Region of the...
Dengue is a vector borne disease caused by virus serotypes DENV-1, DENV-2, DENV-3, and DENV-4, representing a significant public health concern in the Region of the Americas (2,997,097 cases in 2023). This study explores the relationship between dengue incidence and climate changes in the city of São Paulo-Brazil. During the first semester of 2023, Brazil reported the highest number of dengue cases in Americas' Region. Our data reveals a correlation between the high temperature and rainfall season persistence and the extension of dengue incidence into the winter season. The findings highlight the importance of understanding the relationship between climate change and disease transmission patterns to develop effective strategies for prevention and control.
Topics: Humans; Dengue; Dengue Virus; Brazil; Climate Change; Cities
PubMed: 37952859
DOI: 10.1016/j.tmaid.2023.102668 -
Vector Borne and Zoonotic Diseases... Aug 2023The dengue, Zika, and Chikungunya arboviruses have spread in America in the past year, thus becoming global health issues. These viruses are maintained in nature in two...
The dengue, Zika, and Chikungunya arboviruses have spread in America in the past year, thus becoming global health issues. These viruses are maintained in nature in two transmission cycles: an urban cycle, transmitted from hematophagous mosquitoes to humans, and a wild cycle, recorded only in Africa and Asia, involving mosquitoes and nonhuman primates as natural hosts. The evidence shows that these arboviruses infect other wild mammals in America, such as rodents, marsupials, and bats. This study aimed to determine the potential natural infection of arboviruses in bats captured in contrasting sites (tropical forests, urban areas, and caves) in Oaxaca, Mexico. Liver samples were collected from some bats and tested for RNA from dengue, Zika, and Chikungunya with the quantitative real-time PCR assay. We analyzed 162 samples that encompassed 23 bat species. No natural infection with any of the three arboviruses was detected in any sample tested. The existence of a wild cycle of the three arboviruses in the American continent is not ruled out. However, owing to the low or zero prevalence recorded in other studies and the present study, bats are likely involved in the arbovirus transmission cycle as accidental hosts.
Topics: Animals; Humans; Arboviruses; Chikungunya Fever; Chikungunya virus; Chiroptera; Dengue; Dengue Virus; Zika Virus; Zika Virus Infection
PubMed: 37389819
DOI: 10.1089/vbz.2022.0090 -
Nature Microbiology Aug 2023Although dengue virus (DENV) infection typically causes asymptomatic disease, DENV-infected patients can experience severe complications. A risk factor for symptomatic...
Although dengue virus (DENV) infection typically causes asymptomatic disease, DENV-infected patients can experience severe complications. A risk factor for symptomatic disease is pre-existing anti-DENV IgG antibodies. Cellular assays suggested that these antibodies can enhance viral infection of Fcγ receptor (FcγR)-expressing myeloid cells. Recent studies, however, revealed more complex interactions between anti-DENV antibodies and specific FcγRs by demonstrating that modulation of the IgG Fc glycan correlates with disease severity. To investigate the in vivo mechanisms of antibody-mediated dengue pathogenesis, we developed a mouse model for dengue disease that recapitulates the unique complexity of human FcγRs. In in vivo mouse models of dengue disease, we discovered that the pathogenic activity of anti-DENV antibodies is exclusively mediated through engagement of FcγRIIIa on splenic macrophages, resulting in inflammatory sequelae and mortality. These findings highlight the importance of IgG-FcγRIIIa interactions in dengue, with important implications for the design of safer vaccination approaches and effective therapeutic strategies.
Topics: Humans; Animals; Mice; Receptors, IgG; Dengue; Dengue Virus; Macrophages; Immunoglobulin G
PubMed: 37429907
DOI: 10.1038/s41564-023-01421-y -
Methods in Molecular Biology (Clifton,... 2024Dengue virus (DENV) is one of the most important and widespread arthropod-borne viruses, causing millions of infections over the years. Considering its epidemiological...
Dengue virus (DENV) is one of the most important and widespread arthropod-borne viruses, causing millions of infections over the years. Considering its epidemiological importance, efforts have been directed towards understanding various aspects of DENV biology, which have been facilitated by the development of different molecular strategies for engineering viral genomes, such as reverse genetics approaches. Reverse genetic systems are a powerful tool for investigating virus-host interaction, for vaccine development, and for high-throughput screening of antiviral compounds. However, stable manipulation of DENV genomes is a major molecular challenge, especially when using conventional cloning systems. To circumvent this issue, we describe a simple and efficient yeast-based reverse genetics system to recover infectious DENV clones.
Topics: Humans; Dengue Virus; Reverse Genetics; High-Throughput Screening Assays; Genome, Viral; Dengue; Virus Replication
PubMed: 38064036
DOI: 10.1007/978-1-0716-3533-9_14 -
MBio Oct 2023The four dengue virus (DENV) serotypes infect several hundred million people each year. Although primary infection is generally mild, subsequent infection by differing...
The four dengue virus (DENV) serotypes infect several hundred million people each year. Although primary infection is generally mild, subsequent infection by differing serotypes increases the risk for symptomatic disease ranging from fever to life-threatening shock. Despite the availability of licensed vaccines, a comprehensive understanding of antibodies that target the viral envelope protein and protect from infection remains incomplete. In this manuscript, we develop a panel of recombinant viruses that graft each envelope domain of DENV2 onto the DENV4 envelope glycoprotein, revealing protein interactions important for virus viability. Furthermore, we map neutralizing antibody responses after primary DENV2 natural infection and a human challenge model to distinct domains on the viral envelope protein. The panel of recombinant viruses provides a new tool for dissecting the E domain-specific targeting of protective antibody responses, informing future DENV vaccine design.
Topics: Humans; Dengue Virus; Dengue; Antibodies, Viral; Viral Envelope Proteins; Serogroup; Antibodies, Neutralizing
PubMed: 37800919
DOI: 10.1128/mbio.00818-23 -
Frontiers in Immunology 2024Dengue, caused by the dengue virus (DENV), affects millions of people worldwide every year. This virus has two distinct life cycles, one in the human and another in the... (Review)
Review
Dengue, caused by the dengue virus (DENV), affects millions of people worldwide every year. This virus has two distinct life cycles, one in the human and another in the mosquito, and both cycles are crucial to be controlled. To control the vector of DENV, the mosquito , scientists employed many techniques, which were later proved ineffective and harmful in many ways. Consequently, the attention shifted to the development of a vaccine; researchers have targeted the E protein, a surface protein of the virus and the NS1 protein, an extracellular protein. There are several types of vaccines developed so far, such as live attenuated vaccines, recombinant subunit vaccines, inactivated virus vaccines, viral vectored vaccines, DNA vaccines, and mRNA vaccines. Along with these, scientists are exploring new strategies of developing improved version of the vaccine by employing recombinant DNA plasmid against NS1 and also aiming to prevent the infection by blocking the DENV life cycle inside the mosquitoes. Here, we discussed the aspects of research in the field of vaccines until now and identified some prospects for future vaccine developments.
Topics: Animals; Humans; Dengue; Dengue Virus; Dengue Vaccines; Mosquito Vectors; Vaccines, Attenuated; Vaccines, Inactivated; Vaccines, DNA; Viral Vaccines
PubMed: 38487527
DOI: 10.3389/fimmu.2024.1362780 -
Journal of Virology Nov 2023Dengue virus, an arbovirus, causes an estimated 100 million symptomatic infections annually and is an increasing threat as the mosquito range expands with climate...
Dengue virus, an arbovirus, causes an estimated 100 million symptomatic infections annually and is an increasing threat as the mosquito range expands with climate change. Dengue epidemics are a substantial strain on local economies and health infrastructure, and an understanding of what drives severe disease may enable treatments to help reduce hospitalizations. Factors exacerbating dengue disease are debated, but gut-related symptoms are much more frequent in severe than mild cases. Using mouse models of dengue infection, we have shown that inflammation and damage are earlier and more severe in the gut than in other tissues. Additionally, we observed impairment of the gut mucus layer and propose that breakdown of the barrier function exacerbates inflammation and promotes severe dengue disease. This idea is supported by recent data from human patients showing elevated bacteria-derived molecules in dengue patient serum. Therapies aiming to maintain gut integrity may help to abrogate severe dengue disease.
Topics: Animals; Humans; Mice; Culicidae; Dengue Virus; Inflammation; Severe Dengue; Kinetics
PubMed: 37850747
DOI: 10.1128/jvi.01251-23