Why is the discovery of the fifth serotype of dengue denv. Dengue virus envelope protein domain iii hinge determines. Nonetheless, these results show that all four serotypes have been widely circulating in most of indonesia, as is common in hyperendemic countries. The only known vector of denv in new caledonia is aedes aegypti but no study has yet evaluated the competence of new caledonia ae. Majority of the dengue outbreaks are attributed to denv 2 and denv 3 viruses, but denv 1 has not been recorded in major dengue outbreaks. Mar 31, 2014 the occurrence of two consecutive outbreaks due to the same dengue serotype had historically already been observed in nc and other picts7, 11. In humans, dengue infection causes a spectrum of illnesses ranging from asymptomatic, fever, rash, joint pain and other mild symptoms to lifethreatening. Identification of dengue type 1 virus denv1 in koreans. In the following proofofconcept study, we demonstrate the use of the atcc synthetic denv molecular standards in the development of a standard curve for the quantification of viral rna extracted from representative samples of all four denv serotypes. Denv 1 strain predominated the circulation in the nonepidemic period 5. For denv 1 and denv 2, five genotypes have been described.
The dengue virus molecular typing method described by lanciotti and coworkers r. Circulation of dengue virus1 denv1 serotype in delhi. Denv 1 variant strains that escape diagnosis by virus isolation and identification with the typespecific monoclonal antibody 15f3 1 15 reacting with ns1 protein instead of the monoclonal antibody d21f reacting with the e protein 6, 11 have been described to our knowledge, ours is the first description of falsenegative results due to a genetic variant. Infection with a single serotype leads to longterm protective immunity against the homologous serotype but not against other serotypes 1. Df is distributed in most tropical and subtropical areas, where aedes aegypti andor a. Air travel is associated with intracontinental spread of.
Dengue virus denv is the arbovirus with the highest incidence in new caledonia and in the south pacific region. Pcr assay is a nucleic acid amplificationassay that detects denv serotypes 1,2, 3 or 4 rna from human serum or plasma collected from human patients with signs and symptoms consistent with dengue infection. In 1998 and 1999, all four dengue virus serotypes denv14 were recovered from patients in the yangon childrens hospital. The ec 50 values of niclosamide against denv1, denv2, denv3, and denv4 were approximately 1. Dengue virus denv is a singlestranded, positivesense rna virus belonging to the genus flavivirus, family flaviviridae. Infection with 1 denv serotype is believed to provide longterm immunity to the homologous serotype but not to the other serotypes 2. In 20122014, a major denv1 outbreak occurred in new caledonia.
Monoclonal antibodies for specific detection of dengue virus. Molecular characterization and phylogenetic analysis of a. Seqman program in the lasergene software version 5. This indicated that denv 1 had replaced a formerly predominant denv 2. Dengue is a febrile illness transmitted by mosquitoes, causing disease across the tropical and subtropical world. Silent circulation of dengue virus in aedes albopictus. The four denv serotypes can cause a wide range of diseases in humans. Clade replacements in dengue virus serotypes 1 and 3 are. What is different between dengue virus serotypes den1. Onestep realtime rtpcr assays for serotyping dengue virus. Assessment of a dengue1viruslive virus human challenge denv 1lvhc virus strain the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Denv 5 has been detected during screening of viral samples taken from a 37 year old farmer admitted in hospital in sarawak state of malaysia in the year 2007. It is a mosquitoborne, single positivestranded rna virus of the family flaviviridae.
Conclusionwe successfully isolated seven denv serotype 1 strains for the first time in south korea from imported infections. Fulllength genome sequence of a dengue serotype 1 virus. In this study, we used af denv serotype 1 af denv 1 together with af denv 2 on peripheral blood mononuclear cells pbmcs from children in thailand with acute primary or secondary denv 1 infections to analyze the phenotypes of antigenspecific b cells that reflected their exposure or clinical diagnosis. Five serotypes of the virus have been found, all of which can cause the full spectrum of disease. We describe an improvement of the method that allows the. Dengue virus serotype 1 vlp viruslike particle is a new, unique product that has been developed in response to the need for highly immunogenic, concentrated dengue antigens for use in dengue focussed disease research and vaccine development including use as an immunogen. All the isolates were identified as denv serotype 1. New dengue virus type 1 genotype in colombo, sri lanka. Phylogenetic and molecular analyses showed extensive variability among the denv serotypes, which led to the recognition of different genotypes within each serotype.
We report the fullgenome sequence of a dengue serotype 1 virus denv 1 isolated from a traveler returning in july 2019 to italy from democratic republic of congo drc, which is currently affected by ebola and measles outbreaks. Improved molecular detection of dengue virus serotype 1. The various steps in the flavivirus life cycle include 1 virions binding to. Denv 3 and denv 4 have been subdivided into 4 and 2 genotypes, respectively 3,4. In 2000 and 2001, no denv4 was recovered, and denv1 was recovered more frequently than any other serotype. During 19972000 in the pacific region, the serotype recovered from patients was almost exclusively denv2, but during 20002001, virus denv from patients with suspected dengue fever is important both for the diagnosis of the disease and for the implementation of epidemiologic control measures. Clinical significance of the findings are that most of the people living in delhi are probably immune to denv 3 and denv 1 but chances of an outbreak by less prevalent serotypes are still there. Considering that the vector mosquito, aedes albopictus, already exists in south korea, we propose that a vector surveillance program for dengue is urgently needed.
Sequencing and phylogeny of tn dhole dengue virus 1. Freezedried dengue virus 1, strain uve denv 1 20do94, dominican republic, 20, complete genome. Subsequent infection with different serotype of the virus leads. Clinical manifestations of dengue in relation to dengue. Diversity of dengue virus serotype in endemic region of south. A technique for the multiplex detection and typing of denv serotypes 1 to 4 denv 1 to denv 4 from clinical samples by pcrligase detection reaction ldr has been developed. Dengue virus serotypes 1 and 2 responsible for major dengue outbreaks in nepal. Although sporadic imported cases of denv have been documented in yunnan, china since 2000, a complete genome sequence of dengue virus serotype 3 denv 3 imported from laos is still not available. The etiological agent of the disease is an arbovirus of the genus flavivirus and family flaviviridae with four antigenically distinct serotypes denv 1, denv 2, denv 3 and denv 4 1,3,4 which is. Listing a study does not mean it has been evaluated by the u. Overlapping nucleic acid sequences were combined for analysis and edited with the aid of sequencher software gene code corp.
Denv 1 caused a small number of infections in the 2010 outbreak. Neutralization of acidic intracellular vesicles by. We investigated the spatial dynamics of denv 1, denv 2 and denv 3 in brazil by applying a statistical framework to complete genome sequences. The four dengue virus denv serotypes, denv 1, 2, 3, and 4, are endemic throughout tropical and subtropical regions of the world, with an estimated 390 million acute infections annually. The natural history of wildtype dengue virus denv infections of humans. Differences in the transmission of dengue fever by different. The proportion of children with exposure to 1 serotype increased with age, and children were more likely to have been infected with denv 2, denv 1 and denv 3 than denv 4. Clinical, laboratory, and epidemiological features. Dengue is the most widespread mosquitoborne viral disease with an estimated 390 million infections yearly 1, 2. In the last decades, the global distribution of dengue virus denv has expanded to include more geographic areas and all four serotypes denv14 are now present in asia, africa, and the americas. Antibody prevalence data and serotype distribution describe populationlevel risk and inform public health decisionmaking. Pdf dengue virus serotypes 1 and 2 responsible for major. In the present study, denv 1 was primarily present at the study area from 20142017.
Phylogenetic analysis revealed that strain ynpe1 belonged to genotype i. Diversity of dengue virus serotype in endemic region of. The database was established by excel software, the figures were. Denv 2 was mainly detected on both occasions and this serotype caused nearly 95% of denv infections. The etiological agent of the disease is an arbovirus of the genus flavivirus and family flaviviridae with four antigenically distinct serotypes denv1, denv2, denv3.
We performed fulllength genome sequencing to nine isolates representatives from denv1 genotype i and genotype iv. This study revealed that serotype diversity among the three dengue fever endemic areas in south sulawesi did occur. There are four serotypes of the dengue virus denv 1, denv 2, denv 3 and denv 4 differing by 3035% in amino acid sequence. Denv1, 2, and 3 were recovered in approximately similar ratios each year table 2. There are four dengue virus serotypes, denv 1 4, which are genetically and antigenically distinct, although each serotype elicits a similar range of disease manifestations during infection. Dengue virus denv nonstructural protein 1 ns1 is secreted in blood during the acute phase of viremic denv infection. Here, we report the first complete genome sequence and molecular characterization of the imported dengue virus serotype 1 strain ynpe1.
May 14, 2019 epidemiology investigation and phylogenetic analysis of circulating viruses revealed that at least three lineages of dengue virus serotype 2 denv 2 cosmopolitan genotype initiated the outbreak. Epidemiological and molecular features of dengue virus type1. Why is the discovery of the fifth serotype of dengue denv5 not published yet. Dengue virus has four serotypes, namely, denv1, denv2, denv3, and denv4. What is different between dengue virus serotypes den1,den2,den3 and den4.
The four antigenically distinct serotypes denv 1, 2, 3, and 4 cause various forms of illness, ranging from inapparent infection or classic dengue fever df to severe and lifethreatening dengue hemorrhagic feverdengue shock syndrome. The denv complex consists of 4 distinct serotypes, designated denv 1, denv 2, denv 3, and denv 4. Apr 01, 2007 dengue fever df is a vectorborne disease caused by 4 closely related dengue viruses denv 14 1, 2. Denv1 through denv4 are members of the flavivirus group of the virus. Why is the discovery of the fifth serotype of dengue denv5. Dengue virus serotype 1 vlp the native antigen company. Denv 3, which has been found to be the predominant dengue virus circulating to predominant dengue virus serotype circulating in northern india 6,7,8. It has been determined that recent dengue virus epidemics in yunnan, china, originated from southeast asian strains. Complete genome sequence analysis of an imported dengue virus. The development of a novel serotypingns1elisa to identify. Jul 24, 2018 dengue virus denv infection caused by international visitors has become a public health concern in china. Serotype of dengue virus has correlation with severity of dengue fever due to host immune response.
The development of a novel serotypingns1elisa to identify serotypes of dengue virus chunya puttikhunt a,b. Rapid displacement of dengue virus type 1 by type 4, pacific. In contrast, denv 3 has only been detected in one individual in gabon so far caron et al. The first encounter with a dengue virus strain is not often fatal and results in immunity of that strain but only limited or temporary crossimmunity against other strains. Dengue virus 3 genotype 1 associated with dengue fever and. Immunity will form when a person is infected with one type of serotype but does not apply when a secondary infection develops with another serotype. How do dengue viruses infect human cells and replicate themselves. Freezedried dengue virus 1, strain uvedenv120do94, dominican republic, 20, complete genome. However, it failed to detect denv 1 variants in cambodia due to a point mutation. While there are commercially available elisa assays for denv ns1 detection, these tests have limited sensitivity 5070%, do not determine the serotype of the infecting denv, do not detect all four serotypes equally, or are less sensitive in subsequent denv infections.
Infection with a single serotype leads to longterm protective immunity against the homologous serotype but not against other serotypes. The further classification of surabaya denv1 into two different genotypes warrants indepth genomic analysis to study the dynamics of both genotypes and their contribution to virus evolution, virus transmission, and disease. For invitro diagnostic use ivd performance characteristics have been determined. The existing trend contended that serotype replacement, most probably with denv 3 is predicted to take place once the current outbreak subsides. Why is the discovery of the fifth serotype of dengue denv 5 not published yet. Natural history of dengue virus denv1 and denv4 infections. Reemergence of dengue virus serotype 3 infections in gabon. Cdc denv 1 4 realtime rtpcr assay for detection and serotype identification of dengue virus instructions for use package insert catalog no. All statistical data were analyzed using the statistical software jmp in. Dengue virus serotype distribution based on serological. Highly divergent dengue virus type 1 genotype sets a new distance. Denv1 classification of the brun2014 strain was further supported.
Multiple lineages of dengue virus serotype 2 cosmopolitan. Dengue virus type 1 denv1 is one of the four serotypes of the. Assessment of a dengue1viruslive virus human challenge. Atcc development and use of synthetic molecular standards.
Dengue virus 3 genotype 1 associated with dengue fever and dengue hemorrhagic fever, brazil. After recovering from an infection with one dengue serotype, a person has immunity against that particular serotype. Here, we report the first complete genome sequence and genomic characterization of a denv 3. Dengue virus denvns1 serotype 1 antigen, recombinant. The serotypes of dengue virus in endemic areas of makassar, gowa, and maros were denv 2 and denv 4 and no denv 1 and denv 3 serotypes were found. The fifth and latest addition to the existing serotypes of dengue viruses is denv 5 which has been announced in october 20. Thus, persons can be infected with multiple serotypes during their lifetime. Dengue virus and its four serotypes denv 1 to denv 4 infect 390 million people and are implicated in at least 25,000 deaths annually, with the largest disease burden in tropical and subtropical regions. Dengue virus denv is a flavivirus transmitted by aedes spp.
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