When the virus replicates through retroviral means in the infected hosts primates, it causes this noncontagious mosquitoborne illness. Highly divergent dengue virus type 1 genotype sets a new distance. Frontiers potent neutralization ability of a human. In the last decades, the global distribution of dengue virus denv has. The statistical significance, using r software rcoreteam, 20 on. Five serotypes of the virus have been found, all of which can cause the full spectrum of disease. Complete genome sequence of dengue virus serotype 3 from. Natural history of dengue virus denv1 and denv4 infections. Monoclonal antibodies for specific detection of dengue. Therefore, our research has been focused primarily on denv1 ediii in human. The definition of a dengue genotype is based on old studies with partial sequencing and sequenced strains in the public domain. The serotypes of dengue virus in endemic areas of makassar, gowa, and maros were denv2 and denv4 and no denv 1. In 20122014, a major denv 1 outbreak occurred in new caledonia.
Denv nonstructural protein 5 ns5 contains enzymatic activities required for capping and replication of the viral rna genome that occurs in the host cytoplasm. The fifth and latest addition to the existing serotypes of dengue viruses is denv 5 which has been announced in october 20. The colour green, purple, blue and orange represent the number of denv1, denv2, denv3 and igm cases detected respectively. 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. Jun 14, 2016 four antigenically distinct serotypes 14 of dengue viruses denvs cause dengue disease. The impact of insecticide treated curtains on dengue virus. Majority of the dengue outbreaks are attributed to denv2 and denv3 viruses, but denv 1 has not been recorded in major dengue outbreaks.
At the time this study was conducted, tangerang province, indonesia had become a dengue endemic area with all four denv circulates. New genotype invasion of dengue virus serotype 1 drove massive. Dengue is a mosquitotransmitted viral disease endemic to the tropics and subtropics worldwide. Dengue fever is caused by dengue viruses denv from the flavivirus genus and is the most prevalent arboviral disease.
The occurrence of multi serotype dengue viruses had a role in the incidence of concurrent denv infection cases. Time has passed and the virus has diverged into more complex lineages. Dengue virus denv is a mosquitoborne flavivirus found in tropical and subtropical regions. Subsequent infection with different serotype of the virus leads. Nucleotide position numbers correspond to the malaysian. Vector competence of malaysian aedes albopictus with and. An rtpcr panel for rapid serotyping of dengue virus serotypes 1. Dengue virus serotype 1 denv 1 and dengue virus serotype 2 denv2 were isolated from 3 and 14 samples respectively, indicating an ongoing circulation for both serotypes. The consensus sequence was generated by removing low quality base. In the present study, a denv 1 specific human monoclonal antibody hmab, 1g5, isolated from single plasma cells obtained from the peripheral blood mononuclear cells of dengue patients was found to have potent neutralization activity. Although it is a key step in the lifecycle of these viruses, the hostmediated proteolytic maturation of the structural membrane precursor prm glycoprotein is an enigmatic molecular event. Rothman, anuja mathew, dynamics of dengue virus denvspecific b cells in the response to denv serotype 1 infections. Systematically linking serotypespecif icity with epitope mapping in dengue virus sidhartha chaudhury1, gregory d.
The dengue virus denv is a flavivirus that causes the deadly disease dengue fever. Dengue is a major public health issue in tropical and subtropical countries 18, 33. This proteolysis is thought to be mediated by human furin, a member of the. Dengue fever is a febrile disease caused by dengue virus denv, which affects people throughout the tropical and subtropical regions of the world, including indonesia. The prevailing global spread of four dengue virus denv serotypes and the resultant cocirculation of multiple serotypes in the same region have invariably led to conditions supporting the periodic occurrence of simultaneous infection of individuals with more than one denv serotype. The denv 2 serotype is divided into six known genotypes such as asian i ai, asian ii aii, american am. Strip numbers refer to the denv serotype ns1 1 to 4, pandenv p. The dataset consisting of 990 complete genome sequences of strains of dengue virus serotype 2 denv2 was compiled from the dengue virus variation resource at national center for biotechnology information resch et al. Dengue virus denv, a mosquitoborne virus, is responsible for millions of cases of infections worldwide. Dengue virus denv is a mosquitoborne flavivirus that affects 2. A seroconversion was scored when the percent increase in reduction between a negative sample and a subsequent sample was greater than 2fold. The dataset consisting of 990 complete genome sequences of strains of dengue virus serotype 2 denv 2 was compiled from the dengue virus variation resource at national center for biotechnology information resch et al.
Dengue virus denvns1 serotype 1 antibody eastcoast bio. The main mosquito vector, aedes aegypti, thrives in urban areas across these regions, although rural areas are increasingly affected. The existing antibodies to one serotype already exposed to are expanded, and the immune system accepts them as effective. Serotypespecific differences in dengue virus nonstructural. In a few cases, df can progress to lifethreatening dengue hemorrhagic feverdengue shock syndrome dhfdss. Using clinical samples from a denv type 1 epidemic in sri lanka and new. Onestep realtime rtpcr assays for serotyping dengue. Denguespecific serotype related to clinical severity during the 2012. All but 1 of 26 genotypic variants of denv serotypes in a global denv. All statistical data were analyzed using the statistical software jmp in. An rtpcr panel for rapid serotyping of dengue virus serotypes 1 to 4 in human. What is different between dengue virus serotypes den1,den2. More than 4,000 people in spore infected with dengue. Denv 1 has been the mostly dominant serotype for the last 15 years.
Jul 09, 2019 1 new genotype invasion of dengue virus serotype 1 drove massive 2 outbreak in guangzhou, china 3 qinlong jing 1, sean wu 2, zhengjian he 3, lihong yuan 3, mengmeng ma 1, zhijun bai 1. The foi varied markedly in time, which implies that denv transmission dynamics are complex and are best summarized using timedependent transmission parameters. Dengue virus exists as four serotypes dengue 14 and is genetically related to other flaviviruses such as yellow fever and tickborne encephalitis viruses. Maturation of prm is required for denv infectivity. Occurrence of concurrent infections with multiple serotypes. Silent circulation of dengue virus in aedes albopictus. These data suggest that marmosets may prove to be a valuable tool to assess. Denv exists in four immunogenically distinct and geneticallyrelated serotypes denv 1.
Identification of dengue type 1 virus denv1 in koreans. 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. Detection of concurrent infection with multiple dengue virus. Freezedried dengue virus 1, strain uve denv 1 20do94, dominican republic, 20, complete genome. Similar values were obtained with the phylogenetic tree constructed from the. Dengue is the most widespread mosquitoborne viral disease with an estimated 390 million infections yearly 1, 2. The global spread of the virus has made the previous naming of genotypes by geographic association irrelevant. Since 20002001, dengue virus type 1 has circulated in the pacific region. Antibodies to any one denv serotype have the potential to predispose an individual to more severe disease upon infection with a different denv serotype. Infection with one dengue virus serotype provides lifelong immunity to that virus. Number of dengue cases per region in kenya, 20112014. Molecular characterisation of dengue virus type 1 reveals. Detection and serotyping of dengue virus in serum samples by. Subsequent infection with different serotype of the virus.
Denv 1 strain predominated the circulation in the nonepidemic period 5. However, in 2007, type 4 reemerged and has almost completely displaced the strains of type 1. There are four distinct serotypes of denv and infection by one. Pdf new genotype invasion of dengue virus serotype 1. The dengue virus denv serotypes were identified in 243 cases. This virus is part of the family flaviviridae and the genus flavivirus, which presents a total ofour serotypes denvf 1, denv 2, denv 3 and denv 4, so a person can acquire dengue up to 4 times during life. Outbreaks here tend to be caused by the denv 1 serotype as well as denv2, the main dengue virus serotype in the island since 2016. Our method was able to assign all sequences in the wholegenome validation dataset to the right species and denv serotype. A technique for the multiplex detection and typing of denv serotypes 1 to 4 denv 1.
They belong to the genus flavivirus, family flaviviridae of which yellow fever virus. There are four distinct denv serotypes denv14 and infection with any of the. This study showed the circulation of denv serotype 1 in febrile patients and raises. Denv1 classification of the brun2014 strain was further supported by. Dynamics of dengue virus denvspecific b cells in the.
Overall, denv1 was the most dominant serotype followed by denv2 and 3 respectively. Dengue virus surveillance in singapore reveals high viral diversity. Phylogeography and molecular epidemiology of an epidemic. Dengue virus 3 genotype 1 associated with dengue fever and. Dengue, caused by one of the four serologically distinct dengue viruses denv1 to.
Dengue virus denv is transmitted to humans by aedes aegypti mosquitoes. Dengue1 virus and vector competence of aedes aegypti. Viruslike particles derived from pichia pastoris expressed. But they dont bind well enough to eliminate the virus as well as they should. Distribution of dengue virus serotype in tangerang, indonesia. A dengue vaccine must elicit homotypic neutralizing antibodies to all four denv serotypes to avoid the risk of such antibodydependent enhancement in. Dengue virus denv is a singlestranded, positivesense rna virus belonging to the genus flavivirus, family flaviviridae. The four antigenically distinct serotypes denv1, 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 2. Nevertheless, scientists understanding of dengue virus may be simplistic, as rather than distinct antigenic groups, a continuum appears to exist. 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.
Emergence and global spread of a dengue serotype 3, subtype. Pdf new genotype invasion of dengue virus serotype 1 drove. The dominant serotype in malaysia in 2015 was denv. The natural history of wildtype dengue virus denv infections of humans, including. Rapid antigen tests for dengue virus serotypes and zika. Dengue virus denvenv serotype 1 antigen, recombinant. Gubler, in tropical infectious diseases third edition, 2011.
Distributions of the incubation periods of dengue fever with dengue virus denv 4 a. Differences in the transmission of dengue fever by different. Cdc denv 1 4 realtime rtpcr assay for detection and serotype identification of dengue virus instructions for use package insert catalog no. Generation of antins1 mabs to each denv serotype thesupernatantsfromdenvinfectedpsclonedaswine. Phylogenetic analyses were performed using mega software version 6. Dengue virus type 1 denv1 is one of the four serotypes of the arthropod. Conformational changes in intact dengue virus reveal serotype. Rapid displacement of dengue virus type 1 by type 4.
Dengue virus denv is the arbovirus with the highest incidence in new caledonia and in the south pacific region. Emergence and global spread of a dengue serotype 3. Mouse model of dengue virus infection with serotypes 1 and. Denv 1, 3, and 4 have genotypes names by roman numerals i. After removal of specific virus populations using mabcoated magnetic. 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.
Freezedried dengue virus 1, strain uvedenv 1 20do94, dominican republic, 20, complete genome. There are four dengue serotypes denv1 to denv4, and infection with one elicits lifelong immunity to that serotype. We consider that the virus will continue to evolve and new lineages might turn into new serotypes and genotypes in time. Diversity of dengue virus serotype in endemic region of. Dengue virus binding and replication by platelets blood. Background dengue is one of the most common arboviral diseases prevalent worldwide and is caused by dengue viruses genus flavivirus, family flaviviridae.
Chikungunya, dengue and zika viruses have been implicated in recent. But denv3 infections have been rising in the past four. Multiple introductions of dengue virus strains contribute. Distribution of denv serotypes in various regions in kenya varied from 2011 to 2014.
This study revealed that serotype diversity among the three dengue fever endemic areas in south sulawesi did occur. While there are commercially available elisa assays for denv ns1 detection, these tests have limited sensitivity 5070%, do not determine the serotype. This article is from genome announcements, volume 1. As part of the laboratorybased dengue virus surveillance program, clinical. Alignment of nucleotide consensus sequences of the dengue virus serotype 1 denv 1 3. The structural basis for serotypespecific neutralization. Cocirculation of dengue virus serotypes detected in 20 dengue outbreak, myanmar. Dengue fever symptoms present four to six days after being infected by a dengueinfected virus. Patients with the denv1 serotype were more prone to present with several clinical.
Dengue virus denv, a mosquitoborne human pathogen encompassing 4 distinct but closely related serotypes, is a threat to 40% of the worlds population. Frequency distributions of the intrinsic incubation periods of dengue fever cases. The detection and successful typing of dengue virus denv from patients with. Molecular and cellular studies of hostmediated proteolytic. Development and characterization of serotypespecific monoclonal antibodies against the dengue virus4 denv4 nonstructural protein ns1 tesfaye gelanew and elizabeth hunsperger abstract background. Nevertheless, scientists understanding of dengue virus. It is a mosquitoborne, single positivestranded rna virus of the family flaviviridae. Dengue is an enveloped virus, 4060 nm in size, with an isometric nucleocapsid of 2530 nm and an 10. Dengue type 1 viruses circulating in humans are highly infectious. Development and characterization of serotypespecific. The four serotypes of dengue virus denv 1 to 4 cause the most important arthropodborne viral disease of humans. Dengue virus denvserotype 1 antigen, native eastcoast bio.
The proposed ligands were bixin and norbixin, where these molecules are found in the. Phylogenetic analysis revealed the cocirculation of four. We used a phylogenetic approach to evaluate the roles of virus evolution and transport in the emergence of these outbreaks. It contains a positivesense, singlestranded rna genome that is translated and replicated in the host cell cytoplasm, encoding three structural capsid, premembranemembrane, and envelope. Dengue fever, caused by the dengue virus denv, is a major global challenge with 390 million estimated infections annually 1.
Dengue viruses are sustained in tropical and subtropical areas by the vectors aedes aegypti and aedes albopictus 10. The first case of a dual infection with two dengue virus serotypes denv 1 and denv 4 was reported in the serum of a 16yearold male during the 1982 outbreak in puerto rico gubler et al. There are four serotypes of the dengue virus denv 1, denv 2, denv 3 and denv 4 differing by 3035% in amino acid sequence. The database was established by excel software, the figures were. Dengue viruses denvs belong to the flavivirus genus, flaviviridae family, and are single stranded rna viruses, with four immunologically related serotypes denv 1 to 4 and each serotype is phylogenetically divided into different genotypes 21, 45 that have a increased genetic diversity as a. After a primary denv infection, the antibodies elicited confer lifetime protection against that denv serotype.
Analysis of genotype diversity and evolution of dengue virus. The four serotypes of dengue virus denv14 are viruses of global concern. Abstractin 2009, dengue virus serotype 3 denv3 was first detected in guangzhou, china. To test whether competitive displacement of denv 1 by denv4 can be attributed to variations in vector competence, we evaluated the ability of both denv serotypes to be transmitted by ae. Thirtyone sequences of dengue virus serotype 1 and thirtythree sequences of serotype. The four dengue virus denv serotypes are mosquitoborne flaviviruses of humans. Rothman, anuja mathew, dynamics of dengue virus denvspecific b cells in the response to denv serotype 1 infections, using flow cytometry with labeled virions, the journal of infectious diseases, volume 214. Khavrutskii1, valmik desai1, anders wallqvist1 1 biotechnology hpc software applications institute, telemedicine and advanced technology research. Detection and serotyping of dengue viruses in febrile patients. Over the past two decades, dengue virus serotype 3 denv 3 has caused unexpected epidemics of dengue hemorrhagic fever dhf in sri lanka, east africa, and latin america.
Analysis of genotype diversity and evolution of dengue. Clinical significance of the findings are that most of the people living in delhi are probably immune to denv3 and denv 1 but chances of an outbreak by less prevalent serotypes are still there. Dengue virus denv nonstructural protein 1 ns1 is secreted in blood during the acute phase of viremic denv infection. The dominance of denv 1 was the highest followed by denv 3, 2 and 4. A serum sample was considered positive for denv if a dilution neutralized 70% of the test virus at the following cutoff titers. A purified fraction containing denv1 e protein in 6 m guanidine hydrochloride was diluted to a final protein concentration of 0. Denv strains prototype strains of each denv serotype denv1hawaii, denv216681, denv3h87 and denv4h241 21.
Detection and serotyping of dengue virus in serum samples. It is caused by 4 dengue virus serotypes denv14 that. Based on the epidemiological and aetiological characteristics of dengue infection in southern china, denv1 is the most predominant serotype accounting for 60% of all patients, denv2 is occasionally detected, and denv3 and denv4 are seldom observed 4346. The incidence of dengue virus denv infections has been escalating in tropical and subtropical countries, but there are still no effective therapeutic options. Cocirculation of all the four dengue virus serotypes and detection of a novel clade of denv4 genotype i virus in pune, india during 2016 season. For invitro diagnostic use ivd performance characteristics have been determined. 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. The etiological agent of the disease is an arbovirus of the genus flavivirus and family flaviviridae with four antigenically distinct serotypes denv 1, denv2, denv3 and denv4 1,3,4. Using a bespoke method for a 12y longitudinal dataset of serotype specific dengue virus denv infections, we estimated timevarying, serotype specific fois for all four denv serotypes. The detection and successful typing of dengue 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. Over the past two decades, dengue virus serotype 3 denv3 has caused unexpected epidemics of dengue hemorrhagic fever dhf in sri lanka, east africa, and latin america.
We used a phylogenetic approach to evaluate the roles of virus. A computational method for the identification of dengue. Timevarying, serotypespecific force of infection of dengue. Samples collected in this study are in red colour font and strains from thailand are highlighted in light orange. Circulation of dengue virus1 denv1 serotype in delhi. The development of a novel serotypingns1elisa to identify. Characterization of the 20 dengue epidemic in myanmar.