Dengue virus denv is a mosquitotransmitted rna virus responsible for 390 million infections each year and significant morbidity and mortality throughout tropical and subtropical regions of the world. Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by aedes aegypti mosquitoes. Molecular epidemiological and virological study of dengue virus. Dengue viruses denv cause a spectrum of disease in humans, ranging from dengue fever df to a severe, lifethreatening syndrome called dengue hemorrhagic feverdengue shock syndrome dhfdss. Article information, pdf download for alternate hypothesis on the pathogenesis. Role of ns1 antibodies in the pathogenesis of acute. Although vaccines have been used to reduce the global health burden of other.
Ns4b, and ns5 as potential loci for differential pathogenesis. Molecular mechanism of pathogenesis of dengue virus. Current concepts in dengue pathogenesis pdf 92p this note describes about the global impact of dengue and its epidemiology, the clinical presentation of acute dengue and the pathogenesis of acute dengue infection. Molecular evolution and epidemiology of den3 virus. Rhesus monkeys develop viremia similar in pattern to humans after dengue virus challenge but do not develop clinical disease. Efforts to develop a denv vaccine span 70 years and include the work of luminaries of the virus vaccine field. Dendritic cell apoptosis and the pathogenesis of dengue. Dengue virus denv is a member of the flavivirus genus of singlestranded positivesense rna viruses that cause visceral and central nervous system disease in humans. Dengue is the most common vectorborne viral disease in the world, causing an estimated 50 to 100 million infections globally each year and 25,000 deaths. These investigators have taken something old and something new, combining two successful liveattenuated vaccines to produce a chimera. The four dengue viruses are transmitted in tropical countries that circle the globe. Dengue viruses occur as four antigenically related but distinct serotypes.
They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever dhf, or dengue shock syndrome. All can cause syndromes that are selflimited or severe. Beginning in the 1950s, at the time when four different denvs were discovered, a. Differential regulation of 41 th genes was identified and of. The global distribution and burden of dengue nature. More than one third of the worlds population living in tropical and subtropical areas of the world is at risk of dengue infections and as many as 100 million people are yearly infected. Early detection of ns1 has demonstrated efficacy as a diagnostic tool. Dengue virus after entering in the body invades the local macrophages and multiply there. Observations related to the pathogenesis of dengue hemorrhagic fever.
Dengue viruses belong to the family flaviviridae and the four recognized serotypes dengue1, dengue2, dengue3, dengue4 cause a spectrum of disease ranging from an undifferentiated febrile illness to the severe, lifethreatening dengue haemorrhagic feverdengue shock syndrome dhfdss. Pathogenesis of liver involvement during dengue viral infections. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Focusing on the pathogenesis of dengue, a pattern of acute viral infection can be seen. Autoimmune pathogenesis in dengue virus infection viral. In the tropics and subtropics, it is a leading cause of illness and death. The four dengue viruses were isolated from thai infants, all of whom were having a primary dengue infection. Molecular insight into dengue virus pathogenesis and its. The clinical manifestations of dengue are the expression of a constellation of host and viral factors, some acquired, others intrinsic to the individual. Molecular biology and pathogenesis leonard norkin enables students and professionals to develop a deep understanding of fundamental virology by emphasizing principles and discussing virusesorganized by virus family. Dengue fever is one of the major health problems in india. Although dengue infection can be fatal and zika infection in pregnant woman can lead to newborns with microcephaly or an array of neurodegenerative manifestations, the chikungunya infection is a debilitating disease leaving chronic sequelae, which unfortunately has received less attention.
The incidence of dengue has jumped sharply in recent decades as the disease has spread into new geographic regions. In large part, this limitation is related to the lack of a suitable animal model of disease. Dengue is transmitted to humans by aedes aegypti female mosquitoes. In this study, we provide a comprehensive molecular profiling of the involvement of t helper th genes during dengue virus infection of different cell types. Observations related to the pathogenesis of dengue. Finally, the licensure of a dengue vaccine would not guarantee its use by those who need it most. However, relatively little is known about these receptors. Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Viral virulence, infection enhancing antibodies, cytokines and chemical mediators in the setting of intense immune activation are the key players implicated in the pathogenesis of dhf.
The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome dhfdss caused by dengue virus dv infection remain unresolved. Dengue viruses replicate in cells of mononuclear phagocyte lineage, and subneutralizing concentrations of dengue antibody enhance dengue virus infection in these cells. Dengue virus denv is a mosquitotransmitted rna virus that infects an estimated 390 million humans each year. These viruses generally cause a benign syndrome, dengue fever, in the american and african tropics, and a severe syndrome, dengue hemorrhagic feverdengue shock syndrome dhfdss, in southeast asian children.
Cellular receptors in human monocytes and mouse neural cells. Summary much remains to be learned about the pathogenesis of the different manifestations of dengue virus denv infections in humans. Immunopathogenesis of dengue virus infection springerlink. Alternate hypothesis on the pathogenesis of dengue. Monath and colleagues1 have capped years of effort by completing a successful phase 1 trial of the first of several prospective designer vaccines against flavivirus infection. Palmitoylation and polymerization of hepatitis c virus ns4b protein. Dengue virus infection causes dengue fever df, dengue hemorrhagic fever dhf, and dengue. Cell biology of denv infection denv interacts with target cells via one or more host factors that enhance attachment. They may range from subclinical infection to dengue fever, dengue hemorrhagic fever dhf, and eventually dengue shock syndrome dss. Attempts to explain the pathogenesis of dengue in all its complexity must consider all the clinical. Vaccine development as a means to control dengue virus. Generally, dengue is classified as a blood infection and the.
In order to elucidate the role of t lymphocytes in the pathogenesis of dhf, we attempted to determine whether t lymphocytes are activated. Here we investigate the immunoglobulin responses of patients with dengue fever df and. Patients with dhfdss are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and hepatomegaly. The pathogenesis of tuberculosis involves a dynamic interaction between host and pathogen.
Molecular insight into dengue virus pathogenesis and its implications for disease control michael s. Dengue virus denv infections of humans were long thought to be selflimited and of low mortality. This antibodydependent enhancement of infection regulates dengue disease in human beings, although disease severity may also be controlled genetically, possibly by permitting and restricting the growth of virus in monocytes. Towards understanding of the replication and pathogenesis. A role for autophagolysosomes in dengue virus 3 production. Dengue viruses and other members of the flaviviridae family are emerging human pathogens.
Ninety percent of dhf subjects are children less than 15. Despite the global morbidity and mortality associated with denv infection, mechanisms of immune control and viral pathogenesis are poorly understood. Recent evidence has provided further information of neutralizing versus enhancing monoclonal antibodies and their target epitopes on the. Following infection through the bite, cells of the hematopoietic lineage, like dendritic cells, are the first targets of dengue virus infection. The disease is caused by dengue virus which gets transmitted to humans by the bites of infected mosquitoes, aedes ae. Dengue virus denv infection is the most prevalent arthropodborne. Alternate hypothesis on the pathogenesis of dengue hemorrhagic fever dhfdengue shock syndrome dss in dengue virus infection sansanee noisakran and guey chuen perng experimental biology and medicine 2008 233. Cellular receptors in human monocytes and mouse neural cells are main target for the viral infection. Infected local cells then migrate from site of infection to lymph nodes, where monocytes and macrophages are recruited, which become targets of infection. Dengue fever is a major cause of illness and death worldwide. Fortunately, modern intensivecare treatment can be life saving.
Denv subsequently is internalized by endocytosis and fuses with. The disease represents a global health issue as it is endemic in around 100 countries, most of which are in tropical and subtropical areas. American journal of respiratory cell and molecular biology. Actually, viral autoimmunity is involved in the pathogenesis of numerous viral infections, such as human immunodeficiency virus, human hepatitis c virus, human cytomegalovirus, herpes simplex virus, epstein barr virus, and dv. Dengue viral infections postgraduate medical journal. Interaction with specific receptors at the cell surface is one of the first events in the pathogenesis of dengue virus. Genetic approaches in aedes aegypti for control of dengue library. Frontiers the challenges imposed by dengue, zika, and.
Origins of dengue type 2 viruses associated with increased pathogenicity in the americas. Dengue is an important cause of childhood and adult morbidity in asian and latin american countries and its geographic footprint is growing. Dendritic cells dcs are key antigen presenting cells, sensing pathogens, processing and. Although the greatest morbidity and mortality from dengue occurs in children in developing countries, particularly in asia, current dengue vaccines are primarily targeted towards adult travellers and western military personnel. Tuberculosis remains among the worlds great public health challenges, and the advances discussed in this article hold promise for the development of better. Molecular mechanisms and biological significance of ctl avidity. Activation of t lymphocytes in dengue virus infections. The role of ns1specific antibodies in the pathogenesis of dengue virus infection is poorly understood. Molecular profiling of thelper immune genes during dengue.
This disease has reemerged during the past 20 years in the form of an epidemic. The age distribution of cases of dengue hemorrhagic fever and dengue shock syndrome. Antiviral chemistry and chemotherapy predicting zika virus. Denv cycles in nature between its two principal mosquito vectors aedes albopictus or aedes aegypti and humans. Pathogenesis of dengue haemorrhagic fever and its impact. This severe syndrome, which recently has also been. Recent findings the pathogenesis of severe dengue is thought to be immunemediated due to the timing of the clinical manifestations and higher incidence in secondary infections with a heterologous serotype. Pdf dengue fever and dengue haemorrhagic fever are amongst the most. Druggable pockets in dengue fever virus and west nile virus ns3 and ns5 are retained in predicted zika. It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever dhf is much more commonly observed during secondary dengue virus infections than primary infections. The age distribution of cases of dengue hemorrhagic fever and dengue shock syndrome dhfdss in infants under the age of 1 year are reported from bangkok, thailand, and for the first time for ho chi minh city, vietnam. The disease is induced by dengue virus infection resulting from the bite of an infected aedes spp.
One of the most daunting challenges in denv research is the identification of soluble factors that can. Dengue pathogenesis, clinical manifestation, lab diagnosis and treatment pathogenesis of dengue. The exact cause of this large outbreak of dengue fever in china is not yet clear. The common severe syndromedengue haemorrhagic feverdengue shock syndrome dhfdssis characterised by sudden vascular permeability generated by cytokines released when t cells attack dengueinfected cells. The th gene profiles of three human cell types monocytes, tcells and hepatocytes were analyzed simultaneously via arraybased rtpcr upon infection with dengue virus. Dengue is caused by one of four related serotypes of dengue virus and often leads to severe forms of the disease, resulting. A role for autophagolysosomes in dengue virus 3 production in hepg2 cells atefeh khakpoor 1. Pdf autoimmune pathogenesis in dengue virus infection. Annually, 100 million cases of dengue fever and half a million cases of dhf occur worldwide. Dengue viral infections are one of the most important mosquito borne diseases in the world.
Science 1988 jan 29 dengue, which is caused by four antigenically different flaviviruses and is transmitted by mosquitoes, affects as many as 100 million people per year. Plasma leakage and intrinsic coagulopathy are the pathological hall marks in dengue haemorrhagic fever dhf. Dynamic clinical spectrums ranging from asymptomatic, undifferentiated fever, typical dengue fever df, dengue hemorrhagic fever dhf. The oldest purposefullyattenuated viral vaccine, 17d, for yellow fever yf, was. Substantial gaps remain in the comprehensive understanding of the pathogenesis of dengue virus infections. Pdf a new tool for the diagnosis and molecular surveillance of. Four denv serotypes 1, 2, 3, and 4 circulate in tropical and. Alternate hypothesis on the pathogenesis of dengue hemorrhagic. Dengue has been recognized as one of the most important vectorborne human diseases. As both cell tropism and tissue tropism of denv are considered major determinants in the pathogenesis of. From immune to genetics, journal of pediatric infectious diseases on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. A molecular evaluation of dengue virus pathogenesis and.
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