Autoantibodyassociated immunopathogenesis of dengue hemorrhagic fever. Severe dengue most commonly occurs among infants and patients with secondary dengue virus denv infections i. We propose a new hypothesis for the immunopathogenesis for dengue virus infection. Dengue virus denv infection can cause lifethreatening dengue hemorrhagic fever dhf and dengue shock syndrome dss.
Dengue virus infection causes dengue fever df, dengue hemorrhagic fever dhf, and dengue. However, none of these assays can predict the severity of the disease. Dengue virus infections cause significant morbidity and mortality worldwide. Pdf dengue virus infection causes dengue fever df, dengue hemorrhagic fever dhf, and dengue shock syndrome dss, whose pathogeneses are not. It is amongst the most important vectorborne viral disease of humans. Pathogenesis of dengue haemorrhagic fever and its impact. Dengue is a mosquitoborne viral infection caused by 4 related but antigenically distinct dengue virus denv serotypes denv14. Dengue is a potentially fatal acute febrile illness caused by infection with any of four dengue viruses denv1, 2, 3, and 4.
Reevaluation of the pathogenic roles of nonstructural. 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. Dengue virus infection causes aberrant immune responses. 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. 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.
Dengue is a febrile illness caused by a flavivirus transmitted by aedes aegypti or aedes albopictus mosquitoes while taking a blood meal. May 31, 2017 currently, several assays can diagnose acute dengue infection. Severe dengue disease was observed in both primary and secondary infections. Each year, an estimated 390 million people are infected.
T cell immunopathogenesis of dengue virus infection. Dengue is the most common and important arthropodborne viral arboviral illness in humans. Dengue viruses are members of the flaviviridae and have sufficient antigenic similarity to yellow fever virus, japanese encephalitis virus, and west nile virus that previous infection or vaccination may raise crossreactive serum antibodies. Isolation of dengue virus from or demonstration of specific arboviral antigen or genomic sequences in tissue, blood, cerebrospinal fluid csf, or other body fluid by polymerase chain reaction pcr test, immunofluorescence or immunohistochemistry, or seroconversion from negative for dengue virusspecific serum immunoglobulin m igm antibody. Dengue virus denv is a mosquitotransmitted single stranded rna virus belonging to genus flavivirus. The most widely cited hypothesis for this occurrence is antibody dependent enhancement ade of. The disease is caused by four serologically and genetically distinct viruses termed dengue virus denv 1, 2, 3 and 4. There are between 50 and 100 million infections each year, with approximately 500,000 cases admitted to hospital with severe and potentially lifethreatening disease. A better understanding of dengue virus immunopathogenesis is critically needed to optimize candidate vaccines including those currently under development. Immunopathogenesis versus protection in dengue virus. Dengue is a mosquitoborne infection transmitted to humans by aedes aegypti and caused by one of the four closely related virus serotypes of the genus flavivirus, family flaviviridae. Currently, more than half of the human population is at risk of denv infection, and severe dengue remains a leading cause of hospitalization and death among children, particularly in some southeast asian countries 3, 4. 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. Infection by any one of the four serotypes of dengue virus denv remains asymptomatic in the vast majority.
Dengue is among the most important mosquitoborne viral disease in the world. 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. Molecular profiling of thelper immune genes during dengue. Dengue virus belongs to the genus flavivirus, family flaviviridae and has four. Targeting key cells for a dengue virus infection model. Differential regulation of 41 th genes was identified and of which. Aberrant monocyte responses predict and characterize. Dengue is likely underrecognized and underreported in africa because of low awareness by health care providers, other. Each denv has four or more genetic groups or genotypes. Current hypotheses of antibodydependent enhancement, virus virulence, and ifn.
The four dengue viruses were isolated from thai infants, all of whom were having a primary dengue infection. A risk to anyone traveling to a tropical or subtropical region of the world where dengue virus is found. Dengue is the leading mosquitotransmitted viral infection in the world. Dengue is the leading arthropodborne viral infection in the world and represents a major global human health concern. In particular, the results from largescale human efficacy trials will offer outstanding opportunities to refine correlates of protection and design even more effective vaccines.
The great lack of knowledge on dengue pathogenesis is a major. The more dengue virus, the more target cell infection. Transmitted via mosquito bites, the virus typically causes fever, but may also lead to potentially. The disease results from infection with dengue virus denv, which consists of four antigenically distinct serotypes known as denv1, denv2, denv3 and denv4 from the genus flavivirus in the family flaviviridae. Pdf immunopathogenesis of dengue virus infection researchgate. At about one year, the infant is no longer at increased risk. Dengue virus infection causes dengue fever df, dengue hemorrhagic fever dhf, and dengue shock syndrome dss, whose pathogeneses are not clearly understood. 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. Viral load had no association with disease severity but high viral. Molecular profiling of thelper immune genes during dengue virus.
Virus transmitted 1 to human in mosquito saliva 22. Immunopathogenesis versus protection in dengue virus infections. 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. Aberrant monocyte responses predict and characterize dengue. In vivo enhancement of dengue virus infection in rhesus monkeys by passively transferred antibody. Dengue is likely underrecognized and underreported in africa because of low awareness by health care providers, other prevalent febrile illnesses, and lack of diagnostic testing and systematic surveillance.
There are more than 390 million new infections annually. Infections with one of the four serotypes of denv denv14 result in. Denv infection of cells is enhanced by denvantibody complexes formed in the presence of preexisting denvspecific antibodies not shown from a previous denv infection or passive transfer, e. The dengue virus infection is prevalent across the tropical belt in over 100 countries, with 2. The human immunodeficiency virus hiv is probably the most intensively studied virus in the history of biomedical research. Dengue viral infections postgraduate medical journal. Immunopathogenesis of dengue virus infection springerlink. May 03, 2019 zhang jl, wang jl, gao n, chen zt, tian yp, an j. There are 2 main factors affecting severity of dengue fever. Dengue virus denv infection remains the most common arthropodborne viral infection worldwide 1, 2, with a recent global estimate suggesting that 390 million clinical denv cases occur annually.
Pdf t cell immunopathogenesis of dengue virus infection. Immunity and immunopathology in dengue virus infections. Ignoring these data, contemporary models of dengue immunopathogenesis focus on the sequential dengue viral infection phenomenon. 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 denv belongs to the family flaviviridae, genus flavivirus, and is transmitted to humans by aedes mosquitoes, mainly aedes aegypti. How dengue virus infects cells national institutes of. Among a variety of human cell types targeted by denv. The th gene profiles of three human cell types monocytes, tcells and hepatocytes were analyzed simultaneously via arraybased rtpcr upon infection with dengue virus. The battle between infection and host immune responses of. Jun 27, 20 dengue virus denv infection can cause lifethreatening dengue hemorrhagic fever dhf and dengue shock syndrome dss. The clinical manifestations of dengue are the expression of a constellation of host and viral factors, some acquired, others intrinsic to the individual.
Aug 28, 2016 dengue is the leading mosquitotransmitted viral infection in the world. Platelets are destroyed by crossreactive antiplatelet. Monoclonal antibodymediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention. 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.
Request pdf immunopathogenesis of dengue virus infection dengue virus infection causes dengue fever df, dengue hemorrhagic fever dhf, and dengue shock syndrome dss, whose pathogeneses. Hence there is a lacunae in diagnosing dengue virus infection early both in relation to clinical features and laboratory tests. From previous studies, it is known that both antibodies and cytokines induced in response to denv infection are involved in the immunopathogenesis of dhfdss. Dengue virus infection causes aberrant immune responses including cd4cd8 ratio inversion, monocytosis, and atypical. Dengue is an important cause of childhood and adult morbidity in asian and latin american countries and its geographic footprint is growing. Dengue virus infects hundreds of millions of people living in tropical countries every year. Dengue is a globally important arboviral infection transmitted by aedes mosquitoes that endangers an estimated 2. 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. Immunopathogenesis of dengue hemorrhagic fever journal. Differential regulation of 41 th genes was identified and of.
First, work done during world war ii by sabin and others demonstrated longlasting resistance to reinfection with the same denv serotype, in contrast to only shortterm resistance to infection with heterologous serotypes 1. Immune response to dengue virus infection in pediatric patients in. The virus that causes dengue is transmitted by mosquitoes. Dengue virus denv infections of humans were long thought to be selflimited and of. Based on neutralization assay data, four serotypes denv1, denv2, denv3, and denv4 can be distinguished. Dejnirattisai w, jumnainsong a, onsirisakul n, et al. Without treatment, the virus can cause damage to blood and lymph vessels and lead to dengue hemorrhagic fever, which is marked by difficulty breathing, bruising and bleeding from the nose, gums or under the skin. All serotypes can cause illness ranging from asymptomatic, selflimiting flu, dengue fever df, dengue hemorrhagic fever dhf and dengue shock syndrome dss. Distinguishing secondary dengue virus infection from zika. Upregulated expression of beta3 integrin induced by dengue virus serotype 2 infection associated with virus entry into human dermal microvascular endothelial cells. The aberrant immune responses not only impair the immune response to clear the virus, but also result in overproduction of cytokines that affect monocytes, endothelial cells, and hepatocytes. There is an 62 dengue bulletin vol 29, 2005 t cell immunopathogenesis of dengue virus infection overall increase in the levels of t cell activation proliferating in response to the currently markers such as soluble il2 receptor, soluble infecting virus and that it could induce the cd4 and cd8. Epidemiology who reports 30x increase in cases since 1960 no. Immunopathogenesis of dengue virus infection request pdf.
Dengue virus infectionenhancement activity in neutralizing. Crossreacting antibodies enhance dengue virus infection in humans. 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. 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. Although initially believed to be an infection afflicting mainly the paediatric age. Immunopathogenesis of dengue hemorrhagic fever journal of. The dengue virus denv with its four unique serotypes is transmitted by the aedes mosquito vector in tropical countries worldwide. Denv has expanded its global range, with sustained outbreaks in south america, and reintroduction into north america. Clinical features of dengue virus infection are usually nonspecific ranging right from selflimiting disease like fever, headache, myalgia, rashes, and arthralgia to dengue haemorrhagic fever and dengue shock syndrome. The high mutability of rna viruses such as flaviviruses leads to a. 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.
However, not all dengue infection produces dengue hemorrhagic fever. This includes 100 to 200 cases in the united states, mostly in people who have recently traveled abroad. A total of 208 sera from patients suspected of having dengue virus infection were collected and tested for dengue antibody, dengue genome and dengue ns1 antigen. Placental transfer of dengue virus denvspecific antibodies. Nearly 75% of the global denv disease burden is concentrated across south east asia and western pacific, and the incidence had been steadily increasing over the past decade at the rate of. A large number of distinct isolates have been cloned and sequenced, and. 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, currently found in 128 countries, is an important mosquitoborne viral disease posing a threat to health of many global communities. Vascular leakage and abnormal hemorrhage are the two major pathogenic changes found in these patients. 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. Dec 22, 20 monocytes shown here, macrophages, and dendritic cells are the primary targets for dengue virus denv infection. 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. Dengue antibody test, dengue pcr test and dengue antigen test were able to detect dengue virus infection from days 1 to 8 in 72. In the last 50 years, dengue incidence has increased 30fold, worldwide.
The incidence of dengue has increased dramatically in recent decades, with estimates of 40%50% of the worlds population at risk for the. However, that model cannot explain dhfdss during a first dengue. Dengue is a major public health problem worldwide, where an estimated 400 million denv infections and 100 million clinically apparent dengue cases occurred in 2010. The immunopathogenesis of human immunodeficiency virus infection. Dengue fever is a selflimiting viral infection in the majority of cases.
Dengue fever usually starts with a fever, joint pain, rash and nausea. It is transmitted by mosquitoes of the genus aedes, which are widely distributed in subtropical and tropical areas of the world see the image below. Many more cases likely go unreported because some health care providers do not recognize the disease. 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. Fever, body aches, gastro intestinal symptoms, headache, and skin rash and chest symptoms. In this study, we provide a comprehensive molecular profiling of the involvement of t helper th genes during dengue virus infection of. Dengue virus denv infection is a global health threat, with approximately half of the worlds population at risk of being infected and 0. Pathogenesis of dengue haemorrhagic fever and its impact on. Virus infects white 3 blood cells and lymphatic tissues4. The immunopathogenesis of human immunodeficiency virus. Impact of dengue virus denv coinfection on clinical. May 16, 2020 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.