Dengue virus denv 14 represents a major emerging arthropodborne pathogen. Ranil samantha dassanayake department of chemistry, university of colombo, colombo 00300, sri lanka. There are no specific treatments for dengue fever, though medication can be used to control the fever and pain. The first time a person is infected with a dengue virus, they usually have a milder form of the disease called dengue fever. Current and historical conditions indexed list of current and historical nationally notifiable conditions. The crystal structure of the dengue virus rnadependent. Dengue virus rna proteincoding regions and genome organization. Structure and function of the zika virus fulllength ns5. Structure and dynamics of the monomer of protein e of dengue virus type 2 with unprotonated histidine residues l. In general, there are four main morphological virus types. Guerdan, md, mph abstract in september 2009 the first documented, locally acquired cases of dengue fever in eighty years were diagnosed in individuals living in or visiting key west, florida.
Other dengue virus structures in the pdb include immature forms of the virus for instance, in pdb entry 1n6g and structures that include the membranespanning portions of the viral coat pdb entry 1p58. Dengue virus cryoem structure of an antibody that neutralizes dengue virus type 2 bylocking e protein dimers guntur fibriansah,1,2 kristie d. In particular, structural information on vi ral envelope proteins combining both receptorbinding and membrane fusion functions is very scarce. The whole genome phylogenetic tree was constructed by neighborjoining method. In some cases, the virus weakens the circulatory system and can lead to deadly hemorrhaging. The crystal structure of the dengue virus rnadependent rna polymerase catalytic domain at 1. Estimating the probability of dengue virus introduction. Dengue viruses are spread to people through the bite of an infected aedes species ae. Dengue virus denv is responsible for the clinical entity known as dengue that is a great concern for economy and public health of tropical countries.
Only recently has it caused explosive outbreaks in previously unaffected regions, first in oceania and then in the americas since 2015. Interaction of tia1tiar with west nile and dengue virus. Although the 3d architecture of these structures has recently been described, little is known about the cellular pathways required for their formation and expansion. Structure based discovery of dengue virus protease inhibitors. Five serotypes of the virus have been found, all of which can cause the full spectrum of disease. New study reveals structure of zika virus biology, medicine. Matthew henn1, irene bosch2, and eva harris3 in collaboration with the genomic resources in dengue consortium grid 1broad institute. Mar 08, 2002 we report the structure of dengue virus type 2 s1 strain, a vaccine candidate derived from the pr159 isolate hahn et al. Jan 22, 2004 dengue virus enters a host cell when the viral envelope glycoprotein, e, binds to a receptor and responds by conformational rearrangement to the reduced ph of an endosome.
Structure of dengue virus request pdf researchgate. The antigenic structure of zika virus and its relation to. The virus that causes dengue is transmitted by mosquitoes. Structure of dengue virus polymerase, protease and helicase modies et al 2003 dengue virus. They may range from subclinical infection to dengue fever, dengue hemorrhagic fever dhf, and eventually dengue shock syndrome dss. Viruses are often very simple, composed of a small genome that encodes only a few proteins, including a coat that finds a cell and infects it with the genome.
A linear representation, showing distribution of the polypeptide chain among three domains i to iii, colored red. Ns3 helicase from dengue virus specifically recognizes viral. Four distinct serotypes of the dengue virus dengue 1, dengue 2, dengue 3, and dengue 4 exist, with numerous virus strains found worldwide. In large part, this limitation is related to the lack of a suitable animal model of disease. Using as examples zika, chikungunya and dengue, we summarise current knowledge on characteristics of the viruses and their transmission, clinical. Dengue virus denv belongs to the flaviviridae family, it is transmitted by mosquitos of the aedes genus, which has a worldwide distribution. Dengue virus capsid protein functions and its i hibiti b. Whereas the majority of denv infections proceed asymptomatically or result in selflimited dengue fever, an increasing number of patients present more severe. Of special concern is the newly identified link between congenital malformations especially microcephaly and zika virus. The atomic coordinates and structurefactorsofdv1se1411andse1421havebeendepositedin fig 1 the dengue virus e protein. Presenting features may range from asymptomatic fever to dreaded complications such as hemorrhagic fever and shock. Dengue virus nonstructural protein 3 redistributes fatty. The typical symptoms are fever, headache, joint and muscle pain, and a rash.
In this report, we examine the host requirements for denv replication using a focused rnai analysis combined with validation studies using. How dengue virus infects cells national institutes of. A virus infects living cells and forces them to create many new copies of the virus. Build a paper model of dengue virus this paper model of pdb entry 1k4r shows the virus magni. Dengue virus structural differences that correlate with pathogenesis. The nonstructural protein 1 ns1 of the dengue virus interacts with another viral protein called ns4a2k4b to enable viral replication, according to a. The dengue virus structure has sets of three, nearly parallel dimers. The dengue virus belongs to the flaviviridae family of viruses that cause diseases in humans. Wnv is classified in the family flaviviridae, genus flavivirus, along with a number of other human pathogens, including dengue virus dv, japanese encephalitis virus, yellow fever virus, and tickborne encephalitis virus. Dengue is the most common infection caused by viruses transmitted by mosquitoes these are known as arboviral illnesses. The virus core, within a lipid bilayer, has a lessordered structure than the external, icosahedral scaffold of 90 glycoprotein e dimers. Infectivity of dengue virus serotypes 1 and 2 is correlated to. Opening doors to the possibility of developing new vaccines and antiviral agents to fight a host of insectborne diseases, scientists have, for the first time, determined the structure of a family of viruses known as the flaviviruses. Structures of the zika virus envelope protein and its complex with a flavivirus broadly protective antibody.
As shown in the animation, the outside of the dengue virus is made up of glycoproteins arranged in geometric patterns of two, three, and fivefold symmetry. While primary denv2 infections stimulate serotypespecific protective responses, a leading vaccine failed to induce a similar protective response. Amongst the denv proteins, nonstructural protein 1 ns1 is one of the most enigmatic, being required for rna replication, but also secreted from infected cells to. Dengue has seen a 30fold upsurge worldwide between 1960 and 2010. This disease used to be called breakbone fever because it sometimes causes severe joint and muscle pain that feels like bones are breaking.
Replication of dengue virus dengue virus enters host cells by receptormediated endocytosis, which involves binding through the interaction between the surface proteins of virion e and cellular receptors on the surface of target cell. Viruses may cause chronic, persistent infection with. Chart and diagram slides for powerpoint beautifully designed chart and diagram s for powerpoint with visually stunning graphics and animation effects. We report the solution structure of the 200residue homodimer of dengue 2 c protein. Structure of the dengue virus envelope protein after membrane. Dengue, dengue fever df, dengue hemorrhagic fever dhf, dengue shock syndrome dss s new who classification categorizes dengue into dengue, with and without warning signs, and severe. Dengue virus is one of the most widespread mosquitoborne viruses worldwide, with an estimated annual infection rate around 390 million.
Author summary dengue virus denv is a major arthropodborne human pathogen, infecting more than 400 million individuals annually worldwide. Jan 11, 2018 dengue virus denv utilizes the endoplasmic reticulum er for replication and assembling. The images also appear when selecting from individual virus names. A cuteonset high fever, muscle and joint pain, myalgia, cutaneous rash. Dengue virus capsid protein functions and its i hibiti b 14inhibition by pep1423 nuno c. Dengue virus rna structure specialization facilitates host. As both cell tropism and tissue tropism of denv are considered major determinants in the pathogenesis of dengue. Dengue is common in more than 100 countries around the world. Dengue virus serotype 2 denv2 is widespread and responsible for severe epidemics. Feat provides insights into west nile, yellow fever and other flaviviruses. Using human monoclonal antibodies hmabs isolated from dengue cases and structure guided design of a chimeric. Dengue virus exists as a number of different viral forms depending on the degree of precursor membrane prm protein cleavage.
This genus includes also the west nile virus, tickborne encephalitis virus, yellow fever virus, and several other viruses which ma. Pdf structurebased discovery of dengue virus protease. A threedimensional image reconstruction shows that the virion has a wellorganized outer protein shell, a lipid bilayer membrane, and a lesswelldefined inner nucleocapsid core. Pdf dengue virus and its structure a promising target for drug. This lesson covers the differences between the types dengue viruses. The primary role of capsid is to package the viral genome. A prime example is dengue hemorrhagic fever which is likely due to antibody dependent enhancement and t cell activation on reexposure to dengue virus. Structure and dynamics of the monomer of protein e of dengue. The proteinrna interactions within the flavivirus replication complex rc are not fully understood. Dengue fever usually starts with a fever, joint pain, rash and nausea.
Feb 26, 2014 now, new research by liu and her colleagues, presented at the 58th annual biophysical society meeting, which takes place in san francisco last week, could offer vital insight into the mechanism of dengue virus entry into cells and aid vaccine and clinical drug development. Dengue virus denv modifies cellular membranes to establish its sites of replication. Dengue virus is a major threat to health that is transmitted by a tropical mosquito. Dengue virus affects hundreds of millions of people each year around the world, causing a tremendous social and economic impact on affected countries.
Dengue is caused by dengue virus denv, a mosquitoborne flavivirus. Substantial gaps remain in the comprehensive understanding of the pathogenesis of dengue virus infections. In this report, we examine the host requirements for denv replication using a focused rnai analysis combined. A linear representation, showing distribution of the polypeptide chain among three domains i to. It is a rna virus, with tropism for multiple human cells, with a wellestablished and. The rna genome, which contains 10,649 nucleotides, can be modeled using a piece of string approximately 5. The dengue virus structure figure 3c has sets of three, nearly parallel dimers. Three of these are structural proteins that form the coat of the virus and deliver the rna to target cells, and seven of them are nonstructural proteins that orchestrate the production of new viruses once the virus gets inside the cell. In this chapter, the viral structure and life cycle of denv. Dengue viruses are spread by mosquitos and can cause a deadly hemorrhagic fever or a milder illness. Dengue virus is a small virus that carries a single strand of rna as its genome. Helical these viruses are composed of a single type of capsomere stacked around a central axis to form a helical structure, which may have a central cavity, or tube. A risk to anyone traveling to a tropical or subtropical region of the world where dengue virus is found.
Our structure of dengue virus ns3 adenosine triphosphatase atpasehelicase bound to the conserved 5. Yellow fever virus apoi virus aroa virus bagaza virus banzi virus bouboui virus bukalasa bat virus cacipacore virus carey island virus cowbone ridge virus dakar bat virus dengue virus edge hill virus entebbe bat virus gadgets gully virus ilheus virus israel turkey meningoencephalomyelitis virus japanese encephalitis virus jugra virus jutiapa virus kadam virus kedougou virus kokobera virus. To take a closeup look at the interaction of these antibodies with the virus, click on the image for an interactive jsmol. The envelope of the virus is formed when the virus is exiting the cell via budding, and the infectivity of these viruses is mostly dependent on the envelope. A presentation on dengue virus structure, how the virus attacks and spreads in the body, role of heterocyclic drugs in inhibiting the virus and our experiments slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising.
The capsid and entire virus structure can be mechanically physically probed through atomic force microscopy. Dengue fever is common in tropical areas, so take extra precautions if you travel somewhere with this type of climate. Dengue fever dengue hemorrhagic fever dengue fever dengue hemorrhagic fever bruce r. Dengue fever is a virus transmitted to humans through bites from the aedes mosquito, a daybiting mosquito. Sep 07, 20 a presentation on dengue virus structure, how the virus attacks and spreads in the body, role of heterocyclic drugs in inhibiting the virus and our experiments slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. Accumulation of unfolded proteins in the er lumen leads to er stress and unfolded protein response upr. The first structure of a flavivirus has been determined by using a combination of cryoelectron microscopy and fitting of the known structure of glycoprotein e into the electron density map. This virus structure is a conventional icosahedral or helical structure that is surrounded by a lipid bilayer membrane, meaning the virus is encased or enveloped. Mosquitoborne dengue virus denv is a growing public health threat. The viruses belonging to genotype i, iv and v of denv1.
Dengue is a disease caused by infection with one of the four dengue virus serotypes denv1, 2, 3, and 4. The dengue virus, a member of the genus flavivirus of the family flaviviridae, is an arthropodeborne virus that includes four different serotypes den1, den2, den3, and den4. Properties and functions of the dengue virus capsid. Solution structure of dengue virus capsid protein reveals. This enveloped virus contains a positive singlestranded rna genome. To learn about dengue fever, see the national institute of allergy and. Pdf dengue is the most endemic disease of last decade. Without treatment, the virus can cause damage to blood and lymph vessels and lead to dengue hemorrhagic fever, which is marked by difficulty breathing, bruising and bleeding from the nose, gums or under the skin. Oct 05, 2010 dengue virus denv modifies cellular membranes to establish its sites of replication.
Nevertheless, scientists understanding of dengue virus may be simplistic, as rather than distinct antigenic groups, a continuum appears. University of groningen dengue and chikungunya virus van. This animation zooms into a 3d model of dengue virus, moving from the virus s outer structures to its inner core. Dengue virus nonstructural protein 1 modulates infectious. Dengue fever is a mosquitoborne viral illness found throughout the. Fully immature dengue virus particles contain a full complement of prm proteins and are noninfectious, whereas all prm proteins are cleaved in fully mature virus particles. The structural biology of dengue virus request pdf. The virus is transmitted by a type of mosquito aedes aegypti that bites during daylight hours. All four denv serotypes are prevalent in the sub tropical regions of the world and infect 50100 million individuals annually. Cryoem structure of an antibody that neutralizes dengue. Merging this number with the average annual number of officially reported. Dengue is an acute viral illness caused by rna virus of the family flaviviridae and spread by aedes mosquitoes. Ijmrk2 replication of dengue virus in transgenic aedes. In particular, structural information on viral envelope proteins combining both receptorbinding and membrane fusion functions is very scarce.
Molecular cloning methods have led to a greater understanding of the structure of the rna genome and definition of virus specific structural and nonstructural proteins. Rhesus monkeys develop viremia similar in pattern to humans after dengue virus challenge but do not develop clinical disease. Dengue virus nonstructural protein 3 redistributes fatty acid. The overall fit of the 90 tbev e dimer structures to the cryoem map of dengue virus gives a satisfying, closepacking arrangement figures 3b and 3d. Summary much remains to be learned about the pathogenesis of the different manifestations of dengue virus denv infections in humans. Request pdf structure of dengue virus the first structure of a flavivirus has. Nearly 400 million people are infected annually, and no vaccine is currently available. It is a mosquitoborne, single positivestranded rna virus of the family flaviviridae.
A new quaternary structure epitope on dengue virus. Virulence difference of five type i dengue viruses and the intrinsic. The recent emergence and reemergence of viral infections transmitted by vectorszika, chikungunya, dengue, japanese encephalitis, west nile, yellow fever and othersis a cause for international concern. Most of these images are 1200 x 784 pixels and saved qith quality 12 maximum from photoshop. Most infected people experience dengue fever, with terrible headaches and fever and rashes that last 12 weeks. This flavivirus is a single strand rna virus that after their translation and replication in host cells produces three structural and seven nonstructural. Denv is an single stranded rna positivestrand virus of the family flaviviridae, genus flavivirus. Once the virus has entered a host cell, the virus penetrates deeper into the cell and remains inside the endosome. Health experts have known about dengue fever for more than 200 years. Amongst the denv proteins, nonstructural protein 1 ns1 is one of the most enigmatic, being required for rna replication, but also secreted from. Engineering lhrna based molecule to interfere replication of dengue virus in transgenic aedes aegypti mosquitoes.
Dengue virusinduced er stress is required for autophagy. Structures of the zika virus envelope protein and its. Structure of a dengue virus envelope protein latestage. Rebeca ricohesses laboratory is studying the structural rna andor protein and transmission replication in aedes aegypti characteristics of dengue type 2 and type 3 virus variants that have produced dengue hemorrhagic fever in humans throughout the world. Dengue fever is an infectious disease carried by mosquitoes and caused by any of four related dengue viruses. Our new crystalgraphics chart and diagram slides for powerpoint is a collection of over impressively designed datadriven chart and editable diagram s guaranteed to impress any audience. Apr 01, 2016 new study reveals structure of zika virus. Forty percent of the worlds population, about 3 billion people, live in areas with a risk of dengue. Sequence alignment of the c proteins of kunjin virus, the ny99 and nigerian strains of wnv, and dengue the start and end of the trypsincleaved fragment bullets as well as the site of maturation cleavage arrowhead are indicated. These sets associate to form a herringbone configuration on the viral surface. Each year, an estimated 390 million people are infected.
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