Denv infection is a major cause of disease in tropical and subtropical areas, with an estimated 50 million infections occurring each year and more than 2. Dengue virus herd immunity may affect zika virus infection and pathogenesis. There are four dengue virus denv types denv1, denv2, denv3, and denv4, all of which are capable of inducing severe disease dengue hemorrhagic fever dhf dengue shock syndrome dss. A preexisting suboptimal immunity to denv is accepted as being the major risk factor for severe dengue. Alternate hypothesis on the pathogenesis of dengue hemorrhagic fever dhf dengue shock syndrome dss in dengue virus infection sansanee noisakran and guey chuen perng experimental biology and medicine 2008 233. Upregulated expression of beta3 integrin induced by dengue virus serotype 2 infection associated with virus entry into human dermal microvascular endothelial cells. Immunopathogenesis versus protection in dengue virus infections alan l. There are 2 main factors affecting severity of dengue fever. The generally accepted hypothesis explaining the immunopathogenesis of severe dengue is called antibody.
Dengue viral infections are one of the most important mosquito borne viral infections in the world. Dengue virus denv infection is the most common arthropod. The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome dhfdss caused by dengue virus dv infection remain unresolved. Dengue is a febrile illness caused by a flavivirus transmitted by aedes aegypti or aedes albopictus mosquitoes while taking a blood meal. Clinical spectrum among symptomatic infection ranges from undifferentiated fever viral syndrome, dengue fever df, and dengue haemorrhagic fever dhf to the expanded dengue syndrome with isolated organopathy unusual manifestations. Activation of tlr2 and tlr6 by dengue ns1 protein and its implications in the immunopathogenesis of dengue virus infection. The existence of four serotypes of denv with partial immunologic crossreactivity creates the opportunity for individuals to experience multiple acute denv infections over the course of their lifetimes. The immunopathogenesis of dengue haemorrhagic fever and dengue shock syndrome is thought to be mediated by a variety of host factors. The dengue virus denv is a singlestranded, positivesense rna virus of the flavivirus genus that exists in the form of 4 distinct but closely related serotypes denv1 to denv4. Pathogenesis of vascular leak in dengue virus infection malavige.
These aberrant immune responses not only impair the immune response to clear the virus, result in overproduction of cytokines, as well as abnormal production of autoantibodies. Clinical correlates with immunopathogenesis in dengue. Infection by any one of the four serotypes of dengue virus denv remains asymptomatic in the vast majority. Immunopathogenesis of dengue hemorrhagic fever semantic. The presence of disease and high prevalence of antibody to dengue virus in limited serologic surveys suggest endemic dengue virus infection in all or many parts of africa. Human antibody responses after dengue virus infection are highly crossreactive to zika virus lalita priyamvada, kendra m. There are four dengue virus denv types denv1, denv2, denv3, and denv4, all of which are capable of inducing severe disease dengue hemorrhagic fever dhfdengue shock syndrome dss.
As both cell tropism and tissue tropism of denv are considered major determinants in the pathogenesis of. Dengue is likely underrecognized and underreported in africa because of low awareness by health care providers, other. All serotypes can cause illness ranging from asymptomatic, selflimiting flu, dengue fever df, dengue hemorrhagic fever dhf and dengue shock syndrome dss. Dengue is a selflimited, systemic viral infection transmitted between humans by mosquitoes. Certain strains of dengue virus, complexed with nonneutralizing antibodies from previous infection, can enter a greater proportion of cells of the mononuclear lineage, thus increasing virus production.
Aberrant monocyte responses predict and characterize dengue. Dengue virus denv is a mosquitotransmitted single stranded rna virus belonging to genus flavivirus. Among a variety of human cell types targeted by denv. There are several hypotheses explaining dengue pathogenesis. Dengue fever is a mosquitoborne viral disease caused by 1 of 4 closely related but antigenically distinct serotypes of dengue virus, serotypes denv1 through den4. In particular, the results from largescale human efficacy trials will offer outstanding opportunities to refine correlates of protection and design even more effective vaccines. Clinical correlates with immunopathogenesis in dengue haemorrhagic fever dengue shock syndrome psk tan department of anaesthesiology, faculty of medicine, university of malaya, kuala lumpur introduction tory properties of the endothelium.
Detection of postvaccination enhanced dengue virus infection. Severe dengue most commonly occurs among infants and patients with secondary dengue virus denv infections i. Many more cases likely go unreported because some health care providers do not recognize the disease. Denv has expanded its global range, with sustained outbreaks in south america, and reintroduction into north america. Animal models used for dengue tropism and pathogenesis studies. However, none of these assays can predict the severity of the disease. Autoantibodyassociated immunopathogenesis of dengue hemorrhagic fever.
Pathogenesis of dengue viral infections sri lankan journal of. The battle between infection and host immune responses of. The dengue virus denv with its four unique serotypes is transmitted by the aedes mosquito vector in tropical countries worldwide. Wenyang tsai, han ha youn, carlos brites, jihjin tsai, jasmine tyson, celia pedroso, jan felix drexler, mars stone, graham simmons, michael p busch, marion lanteri, susan l stramer, angel balmaseda, eva harris, weikung wang, distinguishing secondary dengue virus infection from zika virus infection with previous dengue by a combination of 3 simple serological tests, clinical. There are four dengue virus serotypes den14 which are.
The clinical manifestations of dengue are the expression of a constellation of host and viral factors, some acquired, others intrinsic to the individual. However, not all dengue infection produces dengue hemorrhagic fever. The development of animal models of dengue virus denv infection and disease has been challenging, as epidemic denv does not naturally infect nonhuman species. Immunopathogenesis of dengue virusinduced redundant cell. Autoimmune pathogenesis in dengue virus infection viral. Infection with any of the four serotypes causes a similar clinical presentation that may vary in severity, depending on a. Serotypecrossreactive dengue virusspecific cytotoxic t lymphocytes ctl induced during a primary dengue virus infection are thought to play a role in the immunopathogenesis of dengue.
The rapidly expanding global footprint of dengue is a public health challenge with an economic burden. Pdf the pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome dhfdss caused by dengue. Pdf immunopathogenesis of dengue virus infection researchgate. Alternate hypothesis on the pathogenesis of dengue. Jun 28, 2019 the dengue virus denv is a singlestranded, positivesense rna virus of the flavivirus genus that exists in the form of 4 distinct but closely related serotypes denv1 to denv4. Author summarydengue disease and its severe manifestations are a growing public health concern, with a third to half the worlds population living in dengueendemic areas.
In contrast, certain immunodeficient mouse models infected with mouse. Clinical manifestations of denv infection and disease severity vary according to different factors. Sep 21, 2012 dengue virus denv infection is the most common arthropod. The virus is endemic in the tropical and subtropical countries of the world, causing diseases classified according to symptoms and severity from mild to severe as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Viruses free fulltext animal models of dengue virus. Dengue viruses cause 50 100 million cases of acute febrile disease every year, including more than 500 000.
Patients with dhfdss are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and hepatomegaly. Thus, if vaccination does not elicit optimal denvspecific immunity, a vaccine might, instead, increase the risk of severe dengue in vaccinated individuals, as seen with the only. 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. Author summarydengue disease and its severe manifestations are a growing public health concern, with a third to half the worlds population living in dengue endemic areas. May 03, 2019 zhang jl, wang jl, gao n, chen zt, tian yp, an j. A better understanding of dengue virus immunopathogenesis is critically needed to optimize candidate vaccines including those currently under development. Hudson, nattawat onlamoon, jaturong sewatanon, srilatha edupuganti, kovit pattanapanyasat, kulkanya chokephaibulkit, mark j. Immunopathogenesis versus protection in dengue virus. An aberrant immune overactivation after dengue virus infection not only impair the immune response to clear the virus, but also result in. Dengue virus infection causes aberrant immune responses. Jul 12, 2016 human antibody responses after dengue virus infection are highly crossreactive to zika virus lalita priyamvada, kendra m. Nonhuman primates nhps can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease.
Immunopathogenesis of dengue hemorrhagic fever semantic scholar. Summary dengue viruses denv, a group of four serologically distinct but related. Dengue fever df is most commonly an acute febrile illness defined by the presence of fever and two or more of the following, retroorbital or ocular pain, headache, rash, myalgia, arthralgia, leukopenia, or hemorrhagic manifestations e. In recent years there have been significant advances in understanding dengue virus dv interactions with target cells such as macrophages, dendritic cells, hepatocytes, and endothelial cells. Similar to sars, macrophage activation is a key component in the pathogenic. Dengue virus infection causes dengue fever df, dengue hemorrhagic fever dhf and dengue shock syndrome dss whose pathogeneses were not clearly understood. Summary much remains to be learned about the pathogenesis of the different manifestations of dengue virus denv infections in humans.
Dengue and dengue hemorrhagic fever clinical microbiology. These antibodies, via antibodydependent enhancement ade of infection, are able to facilitate dengue virus denv growth in fcbearing host cells. A new hypothesis of immunopathogenesis is proposed for the development of the dhfdss. They may range from subclinical infection to dengue fever, dengue hemorrhagic fever dhf, and eventually dengue shock syndrome dss. Dengue viruses denv are mosquitoborne viruses that cause significant morbidity. Cause dengue fever can be caused by any one of four types of dengue virus. Here, circulating antibodies bind to the newly infecting virus but do not neutralize infection. Dengue is an important cause of childhood and adult morbidity in asian and latin american countries and its geographic footprint is growing. Focusing on the pathogenesis of dengue, a pattern of acute viral infection can be seen. Enhancing antibodies are one of the key regulating molecules. The disease is caused by four serologically and genetically distinct viruses termed dengue virus denv 1, 2, 3 and 4.
Wenyang tsai, han ha youn, carlos brites, jihjin tsai, jasmine tyson, celia pedroso, jan felix drexler, mars stone, graham simmons, michael p busch, marion lanteri, susan l stramer, angel balmaseda, eva harris, weikung wang, distinguishing secondary dengue virus infection from zika virus infection with previous dengue by a combination of 3 simple serological tests, clinical infectious. Dengue is the leading arthropodborne viral infection in the world and represents a major global human health concern. Dengue is the leading mosquitotransmitted viral infection in the world. Dengue virus denv is endemic in more than 100 countries with up to 3 billion people in tropical regions of the world at risk of infection. Immunopathogenesis of dengue virus infection springerlink.
This includes 100 to 200 cases in the united states, mostly in people who have recently traveled abroad. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks. Dengue is among the most important mosquitoborne viral disease in the world. Immune responses and immunopathogenesis in infections with dengue virus. Each denv has four or more genetic groups or genotypes. Pdf dengue virus infection causes dengue fever df, dengue hemorrhagic fever dhf. Immunopathogenesis of dengue hemorrhagic fever journal of. Dengue virus denv infections of humans were long thought to be selflimited and of low mortality. Patients with dhfdss are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and. Dengue virus infection causes aberrant immune responses including cd4cd8 ratio inversion, monocytosis, and atypical. We propose a new hypothesis for the immunopathogenesis for dengue virus infection.
Dengue virus infection in humans causes a spectrum of illness ranging from inapparent or mild febrile illness to severe and fatal hemorrhagic disease. Pathogenesis of dengue haemorrhagic fever and its impact on. There are more than 390 million new infections annually. The great lack of knowledge on dengue pathogenesis is a major factor. Animal models of dengue virus infection europe pmc. Dengue virus infection causes dengue fever df, dengue hemorrhagic fever dhf, and dengue shock syndrome dss, whose pathogeneses are not clearly understood. Dengue viral infections represent one of the most rapidly emerging. In the last 50 years, dengue incidence has increased 30fold, worldwide. Jul 03, 2006 the pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome dhfdss caused by dengue virus dv infection remain unresolved. Pdf t cell immunopathogenesis of dengue virus infection. Immune responses and immunopathogenesis in infections with. Immunopathogenesis versus protection in dengue virus infections. Research over the past several years has revealed complex interactions between denv and the human innate and.
Jan 01, 2017 dengue virus infection is a selflimited condition, which is of particular importance in tropical and subtropical regions and for which no specific treatment or effective vaccine is available. In contrast, certain immunodeficient mouse models infected with mouseadapted. Pdf dengue viruses denv are mosquitoborne viruses that cause significant morbidity. Dec 22, 20 dengue viruses denv are mosquitoborne viruses that cause significant morbidity. As both cell tropism and tissue tropism of denv are considered major determinants in the pathogenesis of dengue, there is a. Dengue virus infection is a selflimited condition, which is of particular importance in tropical and subtropical regions and for which no specific treatment or effective vaccine is available. May 31, 2017 currently, several assays can diagnose acute dengue infection.
The mannose receptor mediates dengue virus infection of. Currently, several assays can diagnose acute dengue infection. Pdf immunopathogenesis versus protection in dengue virus. Infection with the murine coronavirus murine hepatitis virus mhv strain jhm results in immunemediated demyelination. Dengue virus denv antibodydependent enhancement of. In french polynesia, the only recognized actively circulating arboviruses were the 4 dengue viruses denv. Pdf autoimmune pathogenesis in dengue virus infection. At about one year, the infant is no longer at increased risk. In vivo enhancement of dengue virus infection in rhesus monkeys by passively transferred antibody. T cell immunopathogenesis of dengue virus infection. An aberrant immune overactivation after dengue virus infection not only impair the immune response to clear the virus, but also. Generally, dengue is classified as a blood infection and the.
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