The structure is mainly similar to that of other flaviviruses such as dengue virus. Dengue is an acute febrile disease caused by the mosquitoborne dengue viruses denvs, consisting of four serotypes denv 1 to 4, that are members of the flaviviridae family, genus flavivirus. The capsid c protein of dengue virus is essential for speci. There were only three significant peaks in the difference map external. Dengue is among the most important mosquitoborne viral disease in the world. Dengue virus is now believed to be the most common arthropodborne disease in the world. The atomic structure of mature zika virus at a resolution of 3. And it looks like very much like other flaviviruses, such as west nile and dengue viruses.
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. 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. 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. Feat provides insights into west nile, yellow fever and other flaviviruses. Structure and function of the nonstructural protein of dengue virus and its applications in antiviral therapy volume. Using human monoclonal antibodies hmabs isolated from dengue cases and structure guided design of a chimeric denv, here we describe the major site on the denv2. Pdf dengue virus and its structure a promising target for drug. 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. Only recently has it caused explosive outbreaks in previously unaffected regions, first in oceania and then in the americas since 2015.
Apr 22, 2016 the ongoing zika virus epidemic is of grave concern because of its apparent links to congenital microcephaly and guillainbarre syndrome. Evidence for a forest maintenance cycle in malaysia, vietnam, and africa. In the old days, solving a virus structure was a big deal. Theseresults suggested that dengue virus maybetransmitted in afashion similar to the jungle cycle of yellow fever virus. Mar 28, 2008 intracellular cleavage of immature flaviviruses is a critical step in assembly that generates the membrane fusion potential of the e glycoprotein. Pdf structure of the dengue virus envelope protein after. Structure of the dengue virus envelope protein after. Structures and functions of the envelope glycoprotein in. Department of health and human services centers for. Pdf dengue is the most endemic disease of last decade. Denv is presently the most common cause of arboviral disease globally, and all four serotypes of.
Dengue virus rna structure specialization facilitates host adaptation plos pathogens, jan 2015 sergio m. Each year, an estimated 390 million people are infected. It is a viral infection where a human acts as the reservoir while the disease is transmitted by mosquitoes. 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 fever can be caused by any one of four types of dengue virus. Dengue virus serotype 2 denv2 is widespread and responsible for severe epidemics. A new quaternary structure epitope on dengue virus. A virus is, after all, a very large assembly of many proteins. Dengue is an acute infectious disease of viral etiology. These results also identified probable drug binding pockets and provide a structural basis for vaccine design. The envelope of the virus is formed when the virus is exiting the cell via budding, and the infectivity of these viruses is.
We report the solution structure of the 200residue homodimer of dengue 2 c. Six months after zika virus became a household word, we now know the threedimensional structure of the virus particle. The first xray diffraction pictures of the crystallised virus were obtained by bernal and fankuchen in 1941. This animation zooms into a 3d model of dengue virus, moving from the viruss outer structures to its inner core. Dengue virus is transmitted between people by female mosquitoes ades aegypti and ades albopidus, which are found throughout the tropical and subtropical regions. A risk to anyone traveling to a tropical or subtropical region of the world where dengue virus is found. 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. Dengue is an arthropod borne virus belongs to family flaviviridae and genus flavivirus. Dengue virus is responsible for 50100 million infections, resulting in nearly 24,000 deaths annually. 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. Insights into dengue virus genome replication twiv.
Dengue virus disease dengue fever, or dengue is a viral disease spread by mosquitoes in many tropical and subtropical parts of the world including africa, asia, south america and occasionally, some parts of northern queensland. You can be infected by at least two if not all four types at different times during your lifetime, but only once by the same type. 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. The crystal structure of the dengue virus rnadependent. A new quaternary structure epitope on dengue virus serotype 2. Finally, the lack of structural constraints in idpsidprs may. The mosquito bites during daytime hours, particularly around the hours of dawn and dusk.
Structure of dengue virus request pdf researchgate. The zika virus surface is similar to that of dengue and related viruses at the nearatomic level, researchers found, but with a notable difference. We report the structure of dengue virus type 2 s1 strain, a vaccine candidate derived from the pr159 isolate hahn et al. Most infected people experience dengue fever, with terrible headaches and fever and rashes that last 12 weeks. For several decades, zika virus zikv was considered an insignificant member of the genus flavivirus of the family flaviviridae 1, 2. Review on dengue viral replication, assembly and entry into the. The 24 a resolution cryoem reconstruction of dengue virus particles figure 1a assumed icosahedral symmetry. Structure of the dengue virus envelope protein after membrane. In some cases, the virus weakens the circulatory system and can lead to deadly hemorrhaging. Dengue pronounced as dengee dengue fever is a highly debilitating mosquitoborne disease mostly seen in tropical countries.
Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea. West nile virus wnv, tickborne encephalitis virus tbev, japanese encephalitis. The disease is caused by four serologically and genetically distinct viruses termed dengue virus denv 1, 2, 3 and 4. Dengue is spread by a type of infected mosquito called the aedes aegypti mosquito. Lab of biosafety level 3, guangdong provincial key laboratory of tropical disease research, school of public health, southern medical university, guangzhou. 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. There are four different strains of the dengue virus. Five serotypes of the virus have been found, all of which can cause the full spectrum of disease.
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. All four denv serotypes have emerged from sylvatic strains in the forests of southeast asia. Nevertheless, scientists understanding of dengue virus may be simplistic, as rather than. Dengue virus is a small virus that carries a single strand of rna as its genome. With cryoelectron microscopy we show that the immature dengue particles undergo a reversible conformational change at low ph that renders them accessible to furin cleavage. Intracellular cleavage of immature flaviviruses is a critical step in assembly that generates the membrane fusion potential of the e glycoprotein. Dengue virus is a major threat to health that is transmitted by a tropical mosquito.
The structure of mature dengue virus particles was determined to a resolution of 9. Viruses may cause chronic, persistent infection with continuous viral replication in the face of an immune response. 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. Rna viruses is intimately linked to membrane structures that enfold around the active repli cation complexes rcs 43. Since dmitri ivanovskys 1892 article describing a nonbacterial pathogen infecting tobacco plants, and the discovery of the tobacco mosaic virus by martinus beijerinck in. The high mutability of rna viruses such as flaviviruses leads to a. 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 tobacco mosaic virus was the first to be crystallised and its structure could, therefore, be elucidated in detail.
It is a mosquito borne, single positivestranded rna virus of the family flaviviridae. 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 crystal structure of the dengue virus rnadependent rna polymerase catalytic domain at 1. A prime example is dengue hemorrhagic fever which is likely due to antibody dependent enhancement and t cell activation on reexposure to dengue virus.
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. In the last 50 years, dengue incidence has increased 30fold, worldwide. 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. Qian xie, bao zhang, jianhai yu, qinghua wu, fangji yang, hong cao and wei zhao affiliation. On the basis of her xray crystallographic pictures, rosalind franklin discovered the full structure of the virus in. The structure suggests that flaviviruses, and by analogy also alphaviruses, employ a fusion mechanism in which the distal. The three e monomers per icosahedral asymmetric unit do not have.
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 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. Transmission dengue virus can be transmitted from the bite of an infected aedes mosquito. Solution structure of dengue virus capsid protein reveals. Using human monoclonal antibodies hmabs isolated from dengue cases and structureguided design of a chimeric denv, here we describe the major site on the denv2. Structure of the dengue virus envelope protein after membrane fusion. Dengue virus 1 den1 was first discovered in japan in the 1940s. This secondary structure leads to the formation of a subgenomic flavivirus rna sfrna through genomic rna degradation by host xrn1.
Presently, the yellow fever virus yfv, dengue virus denv. The other three viruses, den2, den3, and den4, are closely related to den1, but are not recognized as the same virus by. Unstructural biology of the dengue virus proteins wiley. Dengue is mainly found in the tropics because the mosquitoes require a.
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 virus rna structure specialization facilitates host. Viruses may cause chronic, persistent infection with. Apr 05, 2016 six months after zika virus became a household word, we now know the threedimensional structure of the virus particle. The antigenic structure of zika virus and its relation to. 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. The dengue virus is a member of the virus family flaviviridae and is transmitted to people through the bite of the mosquitos aedes aegypti and aedes albopictus. Dengue fever is a virus transmitted to humans through bites from the aedes mosquito, a daybiting mosquito. A threedimensional image reconstruction shows that the virion has a wellorganized outer protein shell, a lipid bilayer membrane, and a lesswelldefined inner nucleocapsid core.
Dengue fever is common in tropical areas, so take extra precautions if you travel somewhere with this type of. Zika virus structure revealed national institutes of health. Each denv has four or more genetic groups or genotypes. The structural biology of dengue virus request pdf. Zika virus structure revealed national institutes of. The virus core, within a lipid bilayer, has a lessordered structure than the external, icosahedral scaffold of 90 glycoprotein e dimers. Dengue virus is one of the most widespread mosquitoborne viruses worldwide, with an estimated annual infection rate around 390 million. 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. The virus core, within a lipid bilayer, has a lessordered structure than the external, icosahedral scaffold of 90.
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