In general, there are four main morphological virus types. Finally, the lack of structural constraints in idpsidprs may. The 24 a resolution cryoem reconstruction of dengue virus particles figure 1a assumed icosahedral symmetry. Additionally, coinfection with and lack of rapid tes. Pdf structure of the dengue virus envelope protein after. Infection of cv1 cellswith this recombinant virus produced dengue virus structural proteins aswell as the nonstructural protein ns.
Four distinct serotypes of the dengue virus dengue 1, dengue 2, dengue 3, and dengue 4 exist, with numerous virus strains found worldwide. The structure of dengue virus was recently described by using cryoelectron microscopy, which permitted visualization of certain viral protein components 3. Viruses may cause chronic, persistent infection with continuous viral replication in the face of an immune response. This same study identified 47 strains of dengue virus. The ns5 protein from dengue virus is bifunctional and contains 900 amino acids. Like other viruses, the dengue virus is a microscopic structure that can only replicate inside a host organism. Structure based design of antivirals against envelope glycoprotein of dengue virus article pdf available in viruses 124. Dengue fever is common in tropical areas, so take extra precautions if you travel somewhere with this type of climate. The other three viruses, den2, den3, and den4, are closely related to den1, but are not recognized as the same virus by. The dengue virus structure has sets of three, nearly parallel dimers. The atomic structure of mature zika virus at a resolution of 3. Nov 26, 2018 usutu virus usuv is a mosquitoborn flavivirus that can infect multiple avian and mammalian species.
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. The dengue virus structure figure 3c has sets of three, nearly parallel dimers. 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. The four closely related dengue viruses den1, den2, den3, and den4 are. A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. In the last 50 years, dengue incidence has increased 30fold, worldwide. It has been shown that the structure of mature zv is arranged in a herringbone pattern with 90 antiparallel envelope dimers 9,10, similar to the structure of dengue virus 11, 12.
Dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and causes 50 million or more cases of infection worldwide each. The genes that encode the dengue virus structural proteins are located at the 5. Dengue virus is a small virus that carries a single strand of rna as its genome. A a central cross section viewed along an icosahedral threefold axis. Yongqian zhao, tingjin sherryl soh, jie zheng, kitti wing ki chan, wint wint phoo, chin chin lee, moon y. 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. Expression of dengue virus structural proteins and nonstructural. Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea. Dengue virus 1 den1 was first discovered in japan in the 1940s. The mosquito bites during daytime hours, particularly around the hours of dawn and dusk. Specifically, we focus on the structure of the premembrane protein, prm and its role in virus assembly, the first fulllength structure of a multidomain dengue virus replication protein, ns3, and the recently solved structures of ns5 methyltransferase and polymerase domains.
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. Dengue viruses are round in shape and covered in a viral envelope. The viral surface envelope e protein functions to initiate the viral infection by recognizing cellular receptors and mediating the subsequent membrane fusion, and is therefore a key virulence factor involved in the pathogenesis of usuv. Zika virus structure revealed national institutes of. Dengue virus is a major threat to health that is transmitted by a tropical mosquito. It is a mosquito borne, single positivestranded rna virus of the family flaviviridae. Insights into dengue virus genome replication twiv. 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. In some cases, the virus weakens the circulatory system and can lead to deadly hemorrhaging.
Mosquitoborne dengue virus denv is a growing public health threat. The capsid and entire virus structure can be mechanically physically probed through atomic force microscopy. Dengue fever is a virus transmitted to humans through bites from the aedes mosquito, a daybiting mosquito. Ns3 protease for the treatment of dengue virus infections by the inhibition. The antigenic structure of zika virus and its relation to. The structural biology of dengue virus request pdf. Each year, an estimated 390 million people are infected.
In the old days, solving a virus structure was a big deal. The high mutability of rna viruses such as flaviviruses leads to a. The disease is caused by four serologically and genetically distinct viruses termed dengue virus denv 1, 2, 3 and 4. Maturation, and fusion through the use of vaccination has proved to be. Lab of biosafety level 3, guangdong provincial key laboratory of tropical disease research, school of public health, southern medical university, guangzhou. Pervasive tertiary structure in the dengue virus rna genome.
Solution structure of dengue virus capsid protein reveals. It is also likely that flexible structures may help viral proteins to evade the host immune system 5558. A virus is, after all, a very large assembly of many proteins. The site corresponding to asn153 is conserved among. Structure and function of the nonstructural protein of dengue virus and its applications in antiviral therapy volume. Five serotypes of the virus have been found, all of which can cause the full spectrum of disease. The crystal structure of the dengue virus rnadependent rna. Structural proteomics of dengue virus sciencedirect. The organization of the major envelope glycoprotein e in the virion was obtained by fitting the atomic structure of the ectodomain from the related tickborne encephalitis tbe e. Mar 28, 2008 the structure of dengue immature virus at ph 6. The virus core, within a lipid bilayer, has a lessordered structure than the external, icosahedral scaffold of 90. 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 envelope comes from the membrane of an infected human cell and is covered with two viral proteins. The capsid c protein of dengue virus is essential for speci. Dengue is among the most important mosquitoborne viral disease in the world. May 09, 2019 the nonstructural protein 1 ns1 of the dengue virus interacts with another viral protein called ns4a2k4b to enable viral replication, according to a study published may 9 in the openaccess. Dengue virus genome encodes 10 viral proteins including 3 structural proteins c, m, and e responsible for viral structure and viral attachment to. A risk to anyone traveling to a tropical or subtropical region of the world where dengue virus is found. We use a new highthroughput rna structure probing technology to identify rna regions with tertiary folds and discover that roughly onethird of the dengue virus rna genome forms higherorder interactions, many in regions functionally important for replication. Each denv has four or more genetic groups or genotypes. Flavivirus rna replication occurs within a replication complex rc that assembles on er membranes and comprises both nonstructural ns viral proteins and host cofactors. We report the structure of dengue virus type 2 s1 strain, a vaccine candidate derived from the pr159 isolate hahn et al. We report the solution structure of the 200residue homodimer of dengue 2 c. 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. Structure of dengue virus request pdf researchgate.
A threedimensional image reconstruction shows that the virion has a wellorganized outer protein shell, a lipid bilayer membrane, and a lesswelldefined inner nucleocapsid core. The envelope of the virus is formed when the virus is exiting the cell via budding, and the infectivity of these viruses is. The structure of mature dengue virus particles was determined to a resolution of 9. Dengue virus is responsible for 50100 million infections, resulting in nearly 24,000 deaths annually.
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. And it looks like very much like other flaviviruses, such as west nile and dengue viruses. Crystal structure of usutu virus envelope protein in the. Qian xie, bao zhang, jianhai yu, qinghua wu, fangji yang, hong cao and wei zhao affiliation. 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. There are two putative nlinked glycosylation sites in the dengue virus eprotein, and the structure shows that they are both used.
Ade has dominated as the explanatory model for severe dengue disease in secondary infections. Many parts of the world have become hyperendemic, implying that all four serotypes of denv cocirculate in the same country, with the consequence that secondary infections are common scenarios. Apr 05, 2016 six months after zika virus became a household word, we now know the threedimensional structure of the virus particle. 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.
Dengue is spread by a type of infected mosquito called the aedes aegypti mosquito. Nevertheless, scientists understanding of dengue virus may be simplistic, as rather than. Department of health and human services centers for. Dengue fever is common in tropical areas, so take extra precautions if you travel somewhere with this type of. The zika virus surface is similar to that of dengue and related viruses at the nearatomic level, researchers found, but with a notable difference. Molecular cloning methods have led to a greater understanding of the structure of the rna genome and definition of virusspecific structural and nonstructural proteins. These results also identified probable drug binding pockets and provide a structural basis for vaccine design. It is a mosquitoborne, single positivestranded rna virus of the family flaviviridae. Zika virus structure revealed national institutes of health.
The darkness of the shading is proportional to the magnitude of the cryoem electron density. A prime example is dengue hemorrhagic fever which is likely due to antibody dependent enhancement and t cell activation on reexposure to dengue virus. Sofia lizeth alcarazestrada1, martha yocupiciomonroy2. As the largest protein component within the flavivirus rc, ns5 plays key. Dengue fever, a neglected emerging disease for which no vaccine or antiviral agents exist at present, is caused by dengue virus, a member of the flavivirus genus which includes several important human pathogens such as yellow fever and west nile viruses. Outbreaks may be explosive or progressive, depending. Dengue is an arthropod borne virus belongs to family flaviviridae and genus flavivirus dengue virus is transmitted between people by female mosquitoes ades aegypti and ades albopidus, which are found throughout the tropical and subtropical regions. The structure provides clues to understanding how zika virus enters human cells and suggests ways to design drugs or vaccines to combat the virus. A crystal structure of the dengue virus ns5 protein reveals a novel interdomain interface essential for protein flexibility and virus replication. Mar 29, 2019 here, the authors provide detailed analyses of viral rna structure in virions and in infected cells for four dengue virus serotypes and four zika virus strains, and identify conserved structures. The three e monomers per icosahedral asymmetric unit do not have.
Dengue virus structural differences that correlate with pathogenesis. There are four different strains of the dengue virus. The virus core, within a lipid bilayer, has a lessordered structure than the external, icosahedral scaffold of 90 glycoprotein e dimers. This was readily justified by the convergence of stable values for angles defining particle orientations, acceptable correlation coefficients, and the good agreement between reconstructions of two independent data sets to at least 24 a resolution. As with other flaviviruses, the dengue virus rna genome is a singlestranded positivesense genome of. Nevertheless, scientists understanding of dengue virus may be simplistic, as rather than distinct antigenic groups, a continuum appears to exist. Structural analysis revealed that 2d22 binds across multiple denv envelope. The crystal structure of the dengue virus rnadependent. 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. However, evidence for ade in humans is indirect and controversial results against ade exist 112, 114. Structure of the dengue virus envelope protein after membrane fusion. Four distinct serotypes of the dengue virus dengue1, dengue2, dengue3, and dengue4 exist, with numerous virus strains found worldwide.
Request pdf structure of dengue virus the first structure of a flavivirus has been determined by using a combination of cryoelectron microscopy and fitting of. Cryoem structure of an antibody that neutralizes dengue. Since dmitri ivanovskys 1892 article describing a nonbacterial pathogen infecting tobacco plants, and the discovery of the tobacco mosaic virus by martinus beijerinck in. Structure and function of the nonstructural protein of. Viruses may cause chronic, persistent infection with. Pdf a crystal structure of the dengue virus ns5 protein. These sets associate to form a herringbone configuration on the viral surface. This animation zooms into a 3d model of dengue virus, moving from the viruss outer structures to its inner core. Most infected people experience dengue fever, with terrible headaches and fever and rashes that last 12 weeks.
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