Cellular receptors in human monocytes and mouse neural cells. Dengue is a mosquitoborne disease caused by infection with dengue virus denv that represents a serious and expanding global health threat. In addition, immunopathogenesis by dvinduced inflammatory activation and autoimmunity may be involved in dengue pathogenesis. Dengue virus and zika virus serological crossreactivity. Dengue virusinduced er stress is required for autophagy activation, viral replication, and pathogenesis both in vitro and in vivo. These viruses generally cause a benign syndrome, dengue fever, in the american and african tropics, and a severe syndrome, dengue hemorrhagic fever dengue shock syndrome dhfdss, in southeast asian children. Pathogenesis of vascular leak in dengue virus infection gathsaurie neelika malavige1,2 and graham s. However, not all dengue infection produces dengue hemorrhagic fever. The most widely cited hypothesis for this occurrence is antibody dependent enhancement ade of. Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by aedes aegypti mosquitoes. Comparative flavivirushost protein interaction mapping. As both cell tropism and tissue tropism of denv are considered major determinants in the pathogenesis of. Dengue virus denv belongs to the family flaviviridae, genus flavivirus, and is transmitted to humans by aedes.
Annually, 100 million cases of dengue fever and half a million cases of dhf occur worldwide. Vaccine development as a means to control dengue virus. Although infection with the dengue virus denv is associated with a self. One of the hypotheses for the seemingly increased pathogenicity of zikv is that crossreactive dengue antibodies can enhance a zikv infection through the principle of antibodydependent. Zika virus is an emerging mosquitoborne virus that was first isolated in zika forest of uganda in 1947. Infection may be asymptomatic or present with a broad range of clinical manifestations including a mild febrile illness to a lifethreatening shock syndrome. They may range from subclinical infection to dengue fever, dengue hemorrhagic fever dhf, and eventually dengue shock syndrome dss. Pdf autoimmune pathogenesis in dengue virus infection. Characteristics of the dengue virus the dengue virus is a single stranded rna virus belonging to the flaviviridae family. This is the same mosquito that transmits dengue, chikungunya and yellow fever one case of possible persontoperson sexual transmission. Diseases caused by dengue virus denv are a major public health problem worldwide, considered one of the infections with more prevalence in tropical and subtropical zones of the world. Volume 175, issue 7, december 2018, pages 19311945.
Dengue fever is a globally important arboviral infection transmitted by the aedes genus of mosquito primarily a aegypti, but also a albopictus, found in tropical and subtropical regions. However, major complications of a zikv infection have recently become apparent for reasons that are still not fully elucidated. Dengue guidelines for diagnosis, treatment, prevention and control dengue guidelines for diagnosis, treatment, prevention and control new edition neglected tropical diseases ntd tdr world health organization hivaids, tuberculosis and malaria htm 20, avenue appia world health organization 1211 geneva 27. Dengue pathogenesis, clinical manifestation, lab diagnosis and treatment pathogenesis of dengue.
However, relatively little is known about these receptors. As both cell tropism and tissue tropism of denv are considered major determinants in the pathogenesis of dengue, there is a. This severe syndrome, which recently has also been identified. 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. Much remains to be learned about the pathogenesis of the different manifestations of dengue virus denv infections in humans. Pathogenesis of dengue haemorrhagic fever and its impact. Dengue virus denv is a member of the flavivirus genus of singlestranded positivesense rna. Dengue virus denv belongs to the family flaviviridae, genus flavivirus, and is transmitted to humans by aedes mosquitoes, mainly aedes aegypti. Based on neutralization assay data, four serotypes denv1, denv2, denv3, and denv4 can be distinguished.
Dengue viruses cause dengue infection, which ranges from mild febrile illness dengue fever, df to fatal hemorrhagic manifestation dengue hemorrhagic fever, dhf, leading to shock syndrome dengue shock syndrome, dss. During this period, virus travels throughout the body. In the last 50 years, dengue incidence has increased 30fold, worldwide. Dengue viral infections are one of the most important mosquito borne diseases in the world. Dengue is a febrile illness caused by infection with one of four dengue viruses denv transmitted by aedes aegypti or aedes albopictus mosquitoes during the taking of a blood meal. One of the main target cells for denv infection is monocytes. Structure, epidemiology, pathogenesis, symptoms, laboratory diagnosis and prevention by editorial team on january 3, 2020 in microbiology, virology the zika virus zikv is a flavivirus related to dengue, yellow fever virus, japanese encephalitis virus and west nile virus. Recent evidence has provided further information of neutralizing versus enhancing monoclonal antibodies and their target epitopes on the. Ogg2 1centre for dengue research, university of sri jayewardenepura, nugegoda, sri lanka and 2mrc human immunology unit, radcliffe department of medicine, weatherall institute of molecular medicine, university of oxford, oxford, uk doi. Explaining the heterogeneity between clinical presentations within a similar crosssection of the population remains a vital area of research. Clinical and laboratory diagnosis of dengue virus infection. Comparative flavivirushost protein interaction mapping reveals mechanisms of dengue and zika virus pathogenesis.
Four denv serotypes 1, 2, 3, and 4 circulate in tropical and. Dengue is a syndrome and its pathogenesis an interplay between virus and host factors that remains incompletely understood. Pathogenesis of vascular leak in dengue virus infection. Efforts to develop a denv vaccine span 70 years and include the work of luminaries of the virus vaccine field. Viral pathogenesis this lecture will define and discuss the basic principles of viral pathogenesis, the entire process by which viruses cause disease. Which usually bite during the morning and late afternoonevening hours.
Beginning in the 1950s, at the time when four different denvs were discovered, a lethal variant. Although dengue is a very old disease but recently an alarming increase has been seen in the geographic range, along with the severity of infection 17. Pathogenesis of dengue haemorrhagic fever and its impact on. Before 1970, only nine countries had experienced severe dengue epidemics. Pathogenesis of dengue viral infections sri lankan journal of. Since then, it has remained mainly in africa, with small and sporadic outbreaks in asia. Beginning in the 1950s, at the time when four different denvs were discovered, a. Summary much remains to be learned about the pathogenesis of the different manifestations of dengue virus denv infections in humans. Dengue is widespread throughout the tropics, with risk factors influenced by local spatial variations of rainfall, temperature, relative humidity, degree of urbanization and quality of vector control services in urban areas.
In a mouse model, low titers of denv and wnv antibodies enhanced zikv viremia, especially in the. Reversely,the immune response of dengue does not resist to the next infection, but promote the severity of the disease from dengue fever to dengue hemorrhagic fever. Aetiology,pathophysiology and diagnosis of dengue infection. Cellular receptors in human monocytes and mouse neural cells are main target for the viral infection. Antibodies against related flaviviruses such as dengue denv and west nile wnv can crossreact with zika virus zikv and could thereby increase disease severity. Interaction with specific receptors at the cell surface is one of the first events in the pathogenesis of dengue virus. Dengue fever is a mosquitoborne viral disease caused by 1 of 4 closely related but antigenically distinct serotypes of dengue virus, serotypes denv1. Denv cycles in nature between its two principal mosquito vectors aedes albopictus or aedes aegypti and humans. Molecular mechanism of pathogenesis of dengue virus. Infected local cells then migrate from site of infection to lymph nodes, where monocytes and macrophages are recruited, which become targets of infection. The most widely cited hypothesis for this occurrence is antibody dependent enhancement ade of disease.
There are four dengue virus serotypes den14 which are closely related. Given that dengue virus infection elicits such a broad range of clinical symptoms, early and accurate laboratory diagnosis is essential for appropriate patient management. The understanding of dengue virus pathogenesis has been. Dengue virus after entering in the body invades the local macrophages and multiply there. So what are the factors associated with the occurrence of dhf. This lecture will define and discuss the basic principles of viral pathogenesis, the entire process by which viruses cause disease. The infection is endemic in more than 100 countries, particularly the south east asia region, western pacific region, and the americas. Ogg2 1centre for dengue research, university of sri jayewardenepura, nugegoda, sri lanka and 2mrc human immunology unit, radcliffe department of medicine, weatherall institute. Plasma leakage and intrinsic coagulopathy are the pathological hall marks in dengue haemorrhagic fever dhf. Dengue virus denv belongs to the family flaviviridae, genus flavivirus, and. Perubatan ud54 slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. Zika virus zikv, which is also transmitted by mosquitoes, has a replication cycle similar to denv saiz et al. Dengue virus and zika virus serological crossreactivity and. Role of monocytes in the pathogenesis of dengue springerlink.
In large part, this limitation is related to the lack of a suitable animal model of disease. The dengue virus nonstructural1 protein ns1 generates antibodies to common epitopes on human blood clotting, integrinadhesin proteins and binds to human endothelial cells. Pathogenesis and pathophysiology of dengue hemorrhagic fever. Jul 03, 2006 the pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome dhfdss caused by dengue virus dv infection remain unresolved. Dengue igm and igg responses role of ige in pathogenesis total and dengue specific ige antibody levels are higher in dhf and dss patients compare to dd patients total ige levels significantly higher in those previously exposed to dengue infections during severe dengue infection. Initial infection with a particular serotype is known as primary infection, which is usually. Preexisting immunity to zika virus zikv or dengue virus denv may alter the course of their infection, and here we use robust mouse models to examine pathological outcomes following passive immunization, sequential crossinfection, or vaccination with inactivated virus. Dengue virusinduced er stress is required for autophagy. In general, the presence of denv in several organs was not associated with gross or microscopic evidence of severe organ pathology 17, which is in agreement with the pathogenesis of dhfdss. There are 2 main factors affecting severity of dengue fever. Viral pathogenesis and immunopathogenesis of dv infection are the causes of dhfdss in dv infection. Jun 23, 2017 zika virus zikv is a reemerging virus that has recently spread into dengue virus denv endemic regions and crossreactive antibodies abs could potentially affect zikv pathogenesis.
Il6, together with il1, is a potent inducer of fever. Dengue viral infections postgraduate medical journal. Nov 25, 2015 read the original article in full on fresearch. Pdf much remains to be learned about the pathogenesis of the different manifestations of dengue virus denv infections in humans. The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome dhfdss caused by dengue virus dv infection remain unresolved. Dengue virus denv is transmitted by mosquitoes and infects nearly 400 million people annually bhatt et al.
Zika virus zikv is a reemerging virus that has recently spread into dengue virus denv endemic regions and crossreactive antibodies abs could potentially affect zikv pathogenesis. Dengue pathogenesis, clinical manifestation, lab diagnosis. Although vaccines have been used to reduce the global health burden of other. Molecular insight into dengue virus pathogenesis and its. Dawn of a new era read the latest article version by scott b. Zika virus is transmitted to people through the bite of an infected mosquito from the aedes genus, mainly aedes aegypti in tropical regions. Dengue is among the most important mosquitoborne viral disease in the world. Although dengue is a very old disease but recently an alarming increase has been seen in the geographic range, along with the severity of. Dengue virus denv infections of humans were long thought to be selflimited and of low mortality. Substantial gaps remain in the comprehensive understanding of the pathogenesis of dengue virus infections. This severe syndrome, which recently has also been.
Viral disease is a sum of the effects on the host of virus replication and of the immune response. 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. Patients with dhfdss are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and. The more dengue virus, the more target cell infection. Increased virus load by ade and virus variation may directly cause an effect. Enhancement of zika virus pathogenesis by preexisting. Dengue fever is one of the major health problems in india. Pdf pathogenesis and pathophysiology of dengue hemorrhagic. Despite the intense research in the pathogenesis of denv, this feature is not well understood. Pathogenesis of dhfdss risk factors reported for dhf most cases of dengue fever are selflimited in their course and never progress to dengue hemorrhagic fever.
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. Nov 25, 2015 dengue virus denv infections of humans were long thought to be selflimited and of low mortality. Ninety percent of dhf subjects are children less than 15 years of age. Comparative flavivirushost protein interaction mapping reveals mechanisms of dengue and zika virus pathogenesis graphical abstract highlights d comparative apms reveals shared and virusspeci.
Dengue pathogenesis, clinical manifestation, lab diagnosis and treatment. Pdf dengue virus denv infections of humans were long thought to be self limited and of low mortality. 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. 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. Rhesus monkeys develop viremia similar in pattern to humans after dengue virus challenge but do not develop clinical disease. Autoimmune pathogenesis in dengue virus infection viral. Classification schemes overview in 1997, the world health organization who published a classification scheme describing three categories of symptomatic denv infection. Pathogenesis of dengue fever and dhf dengue fever develops from dengue virus infection following a mosquito bite.
Prevention and treatment and dengue virus infection. Dhf can occur in primary infection with certain genetic strains of virus. The disease is caused by four serologically and genetically distinct viruses termed dengue virus denv 1, 2, 3 and 4. Generally, when we get an infection, our bodies have an immune response for antigen clearance at that time and memory for the next infection resistance in the future. Zika virus zikv has been known for decades to circulate in africa and asia. Interest in viral pathogenesis stems from the desire to treat or eliminate viral diseases that affect humans. Pathogenesis people bitten by aedes aegypti mosquito are diagnosed with high fever and severe joint pain that are the common symptoms of dengue fever 16. Ninety percent of dhf subjects are children less than 15. Apr 03, 2016 this video aims to describe the mode of replication of dengue virus and the pathophysiology of dengue. Pathogenesis of dhfstep 1 homologous antibodies form non infectious complexes 1 1 1 1 dengue 1 virus neutralizing antibody to dengue 1 virus nonneutralizing antibody 1 complex formed by neutralizing antibody and virus. Apr 14, 2017 antibodies against related flaviviruses such as dengue denv and west nile wnv can crossreact with zika virus zikv and could thereby increase disease severity.
Dec 08, 2017 dengue pathogenesis, clinical manifestation, lab diagnosis and treatment pathogenesis of dengue. Each denv has four or more genetic groups or genotypes. The possible role of crossreactive dengue virus antibodies. Sep 20, 2018 diseases caused by dengue virus denv are a major public health problem worldwide, considered one of the infections with more prevalence in tropical and subtropical zones of the world. Infection with any of the 4 dengue virus serotypes results in a diverse range of symptoms, from mild undifferentiated fever to lifethreatening hemorrhagic fever and shock. In a mouse model, low titers of denv and wnv antibodies enhanced zikv viremia, especially. This video aims to describe the mode of replication of dengue virus and the pathophysiology of dengue. Patients with dhfdss are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and hepatomegaly. Severe dengue most commonly occurs among infants and patients with secondary dengue virus denv infections i. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever dhf, or dengue shock syndrome.
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