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Francis A Ennis - One of the best experts on this subject based on the ideXlab platform.
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spatial and temporal circulation of Dengue Virus serotypes a prospective study of primary school children in kamphaeng phet thailand
American Journal of Epidemiology, 2002Co-Authors: Timothy P Endy, David W Vaughn, Ananda Nisalak, Supamit Chunsuttiwat, Daniel H Libraty, Sharone Green, Alan L Rothman, Francis A EnnisAbstract:Dengue Virus occurs as four distinct serotypes, each of which causes epidemics throughout the tropical and subtropical regions of the world. Few studies have examined co-circulation of multiple Dengue Virus serotypes in a well-defined cohort population over time and their capacity to produce severe Dengue disease. In this paper, the authors report the details and findings of the first 3 years (1998-2000) of an ongoing prospective study of Dengue Virus transmission and disease severity in a cohort of children in northern Thailand. A total of 108 Dengue Virus isolates were obtained from 167 acute Dengue Virus infections; 23% were DEN-1, 35% were DEN-2, 41% were DEN-3, and 1 % were DEN-4. Despite the proximity of the schools, there was marked spatial and temporal clustering of transmission of each Dengue serotype. Serotype-specific antibody levels prior to the Dengue transmission season were not predictive of the incidence of Dengue Virus infections or the predominant serotype transmitted at individual schools. All Dengue serotypes produced severe Dengue illness, although DEN-3 produced more severe symptoms than the other Dengue serotypes. The authors' findings emphasize the complexity of Dengue serotype-specific Virus transmission and severe Dengue disease and have important implications for Dengue control and vaccine development.
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epidemiology of inapparent and symptomatic acute Dengue Virus infection a prospective study of primary school children in kamphaeng phet thailand
American Journal of Epidemiology, 2002Co-Authors: Timothy P Endy, David W Vaughn, Ananda Nisalak, Supamit Chunsuttiwat, Daniel H Libraty, Sharone Green, Alan L Rothman, Francis A EnnisAbstract:Dengue Viruses are a major cause of morbidity in tropical and subtropical regions of the world. Knowledge about the epidemiology and host determinants of inapparent and severe Dengue Virus infections is limited. In this paper, the authors report findings from the first 3 years of a prospective study of Dengue Virus transmission and disease severity conducted in a cohort of 2,119 elementary school children in northern Thailand. A total of 717,106 person-school days were observed from 1998 to 2000. The incidence of inapparent and of symptomatic Dengue Virus infection was 4.3% and 3.6% in 1998, 3.2% and 3.3% in 1999, and 1.4% and 0.8% in 2000, respectively. Symptomatic Dengue Virus infection was responsible for 3.2%, 7.1%, and 1.1% of acute-illness school absences in 1998, 1999, and 2000, respectively. The early symptom complex of acute Dengue Virus infection is protean and difficult to distinguish from other causes of febrile childhood illnesses. The authors' results illustrate the spatial and temporal diversity of Dengue Virus infection and the burden of Dengue disease in schoolchildren in Thailand. Their findings increase understanding of Dengue Virus transmission and disease severity in a well-defined cohort population and offer a study design in which to test the efficacy of potential Dengue vaccines.
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human dendritic cells are activated by Dengue Virus infection enhancement by gamma interferon and implications for disease pathogenesis
Journal of Virology, 2001Co-Authors: Daniel H Libraty, Timothy P Endy, Sathit Pichyangkul, Chuanpis Ajariyakhajorn, Francis A EnnisAbstract:The ability of dendritic cells (DCs) to shape the adaptive immune response to viral infection is mediated largely by their maturation and activation state as determined by the surface expression of HLA molecules, costimulatory molecules, and cytokine production. Dengue is an emerging arboviral disease where the severity of illness is influenced by the adaptive immune response to the Virus. In this report, we have demonstrated that Dengue Virus infects and replicates in immature human myeloid DCs. Exposure to live Dengue Virus led to maturation and activation of both the infected and surrounding, uninfected DCs and stimulated production of tumor necrosis factor alpha (TNF-α) and alpha interferon (IFN-α). Activation of the Dengue Virus-infected DCs was blunted compared to the surrounding, uninfected DCs, and Dengue Virus infection induced low-level release of interleukin-12 p70 (IL-12 p70), a key cytokine in the development of cell-mediated immunity (CMI). Upon the addition of IFN-γ, there was enhanced activation of Dengue Virus-infected DCs and enhanced Dengue Virus-induced IL-12 p70 release. The data suggest a model whereby DCs are the early, primary target of Dengue Virus in natural infection and the vigor of CMI is modulated by the relative presence or absence of IFN-γ in the microenvironment surrounding the Virus-infected DCs. These findings are relevant to understanding the pathogenesis of Dengue hemorrhagic fever and the design of new vaccination and therapeutic strategies.
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bystander target cell lysis and cytokine production by Dengue Virus specific human cd4 cytotoxic t lymphocyte clones
Journal of Virology, 1999Co-Authors: Susan J Gagnon, Francis A Ennis, Alan L RothmanAbstract:Dengue hemorrhagic fever, the severe form of Dengue Virus infection, is believed to be an immunopathological response to a secondary infection with a heterologous serotype of Dengue Virus. Dengue Virus capsid protein-specific CD4(+) cytotoxic T-lymphocyte (CTL) clones were shown to be capable of mediating bystander lysis of non-antigen-presenting target cells. After activation by anti-CD3 or in the presence of unlabeled antigen-presenting target cells, these clones could lyse both Jurkat cells and HepG2 cells as bystander targets. Lysis of HepG2 cells suggests a potential role for CD4(+) CTL in the liver involvement observed during Dengue Virus infection. Three CD4(+) CTL clones were demonstrated to lyse cognate, antigen-presenting target cells by a mechanism that primarily involves perforin, while bystander lysis occurred through Fas/Fas ligand interactions. In contrast, one clone used a Fas/Fas ligand mechanism to lyse both cognate and bystander targets. Cytokine production by the CTL clones was also examined. In response to stimulation with D2 antigen, CD4(+) T-cell clones produced gamma interferon, tumor necrosis factor alpha (TNF-alpha) and TNF-beta. The data suggest that CD4(+) CTL clones may contribute to the immunopathology observed upon secondary Dengue Virus infections through direct cytolysis and/or cytokine production.
Timothy P Endy - One of the best experts on this subject based on the ideXlab platform.
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intracellular cytokine production by Dengue Virus specific t cells correlates with subclinical secondary infection
The Journal of Infectious Diseases, 2011Co-Authors: Steven C Hatch, Timothy P Endy, Daniel H Libraty, Stephen J Thomas, Anuja Mathew, James A Potts, Pamela P Pazoles, Robert V Gibbons, Alan L RothmanAbstract:The pathophysiology of Dengue Virus infection remains poorly understood, although secondary infection is strongly associated with more severe disease. In the present study, we performed a nested, case-control study comparing the responses of pre-illness peripheral blood mononuclear cells between children who would subsequently develop either subclinical or symptomatic secondary infection 6–11 months after the baseline blood samples were obtained and frozen. We analyzed intracellular cytokine production by CD4+ and CD8+ cells in response to stimulation with Dengue antigen. We found higher frequencies of Dengue Virus–specific TNFα, IFNγ-, and IL-2–producing T cells among schoolchildren who subsequently developed subclinical infection, compared with those who developed symptomatic secondary Dengue Virus infection. Although other studies have correlated immune responses during secondary infection with severity of disease, to our knowledge this is the first study to demonstrate a pre-infection Dengue-specific immune response that correlates specifically with a subclinical secondary infection.
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spatial and temporal circulation of Dengue Virus serotypes a prospective study of primary school children in kamphaeng phet thailand
American Journal of Epidemiology, 2002Co-Authors: Timothy P Endy, David W Vaughn, Ananda Nisalak, Supamit Chunsuttiwat, Daniel H Libraty, Sharone Green, Alan L Rothman, Francis A EnnisAbstract:Dengue Virus occurs as four distinct serotypes, each of which causes epidemics throughout the tropical and subtropical regions of the world. Few studies have examined co-circulation of multiple Dengue Virus serotypes in a well-defined cohort population over time and their capacity to produce severe Dengue disease. In this paper, the authors report the details and findings of the first 3 years (1998-2000) of an ongoing prospective study of Dengue Virus transmission and disease severity in a cohort of children in northern Thailand. A total of 108 Dengue Virus isolates were obtained from 167 acute Dengue Virus infections; 23% were DEN-1, 35% were DEN-2, 41% were DEN-3, and 1 % were DEN-4. Despite the proximity of the schools, there was marked spatial and temporal clustering of transmission of each Dengue serotype. Serotype-specific antibody levels prior to the Dengue transmission season were not predictive of the incidence of Dengue Virus infections or the predominant serotype transmitted at individual schools. All Dengue serotypes produced severe Dengue illness, although DEN-3 produced more severe symptoms than the other Dengue serotypes. The authors' findings emphasize the complexity of Dengue serotype-specific Virus transmission and severe Dengue disease and have important implications for Dengue control and vaccine development.
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epidemiology of inapparent and symptomatic acute Dengue Virus infection a prospective study of primary school children in kamphaeng phet thailand
American Journal of Epidemiology, 2002Co-Authors: Timothy P Endy, David W Vaughn, Ananda Nisalak, Supamit Chunsuttiwat, Daniel H Libraty, Sharone Green, Alan L Rothman, Francis A EnnisAbstract:Dengue Viruses are a major cause of morbidity in tropical and subtropical regions of the world. Knowledge about the epidemiology and host determinants of inapparent and severe Dengue Virus infections is limited. In this paper, the authors report findings from the first 3 years of a prospective study of Dengue Virus transmission and disease severity conducted in a cohort of 2,119 elementary school children in northern Thailand. A total of 717,106 person-school days were observed from 1998 to 2000. The incidence of inapparent and of symptomatic Dengue Virus infection was 4.3% and 3.6% in 1998, 3.2% and 3.3% in 1999, and 1.4% and 0.8% in 2000, respectively. Symptomatic Dengue Virus infection was responsible for 3.2%, 7.1%, and 1.1% of acute-illness school absences in 1998, 1999, and 2000, respectively. The early symptom complex of acute Dengue Virus infection is protean and difficult to distinguish from other causes of febrile childhood illnesses. The authors' results illustrate the spatial and temporal diversity of Dengue Virus infection and the burden of Dengue disease in schoolchildren in Thailand. Their findings increase understanding of Dengue Virus transmission and disease severity in a well-defined cohort population and offer a study design in which to test the efficacy of potential Dengue vaccines.
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human dendritic cells are activated by Dengue Virus infection enhancement by gamma interferon and implications for disease pathogenesis
Journal of Virology, 2001Co-Authors: Daniel H Libraty, Timothy P Endy, Sathit Pichyangkul, Chuanpis Ajariyakhajorn, Francis A EnnisAbstract:The ability of dendritic cells (DCs) to shape the adaptive immune response to viral infection is mediated largely by their maturation and activation state as determined by the surface expression of HLA molecules, costimulatory molecules, and cytokine production. Dengue is an emerging arboviral disease where the severity of illness is influenced by the adaptive immune response to the Virus. In this report, we have demonstrated that Dengue Virus infects and replicates in immature human myeloid DCs. Exposure to live Dengue Virus led to maturation and activation of both the infected and surrounding, uninfected DCs and stimulated production of tumor necrosis factor alpha (TNF-α) and alpha interferon (IFN-α). Activation of the Dengue Virus-infected DCs was blunted compared to the surrounding, uninfected DCs, and Dengue Virus infection induced low-level release of interleukin-12 p70 (IL-12 p70), a key cytokine in the development of cell-mediated immunity (CMI). Upon the addition of IFN-γ, there was enhanced activation of Dengue Virus-infected DCs and enhanced Dengue Virus-induced IL-12 p70 release. The data suggest a model whereby DCs are the early, primary target of Dengue Virus in natural infection and the vigor of CMI is modulated by the relative presence or absence of IFN-γ in the microenvironment surrounding the Virus-infected DCs. These findings are relevant to understanding the pathogenesis of Dengue hemorrhagic fever and the design of new vaccination and therapeutic strategies.
Ichiro Kurane - One of the best experts on this subject based on the ideXlab platform.
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importation of Dengue Virus type 3 to japan from tanzania and cote d ivoire
Emerging Infectious Diseases, 2010Co-Authors: Meng Ling Moi, Tomohiko Takasaki, Akira Kotaki, Shigeru Tajima, Changkweng Lim, Mitsuo Sakamoto, Hajime Iwagoe, Kenichiro Kobayashi, Ichiro KuraneAbstract:Travelers can introduce Viruses from disease-endemic to non–disease-endemic areas. Serologic and virologic tests confirmed Dengue Virus infections in 3 travelers returning to Japan: 2 from Tanzania and 1 from Cote d’Ivoire. Phylogenetic analysis of the envelope gene showed that 2 genetically related Virus isolates belonged to Dengue Virus type 3 genotype III.
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Dengue Virus type 2 isolated from an imported Dengue patient in japan first isolation of Dengue Virus from nepal
Journal of Travel Medicine, 2008Co-Authors: Tomohiko Takasaki, Akira Kotaki, Shigeru Tajima, Changkweng Lim, Kiyomi Nishimura, Yukiyoshi Sato, Atsuko Tokuda, Mikako Ito, Reiko Nerome, Ichiro KuraneAbstract:We report the isolation of Dengue Virus type 2 from a Dengue patient returning to Japan from Nepal in October, 2004. This is the first isolate of Dengue Virus in Nepal. According to nucleotide homology, the Virus was closest to a Dengue Virus type 2 isolate from India.
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Dengue Virus cross reactive hemagglutination inhibition antibody responses in patients with primary Dengue Virus infection
Japanese Journal of Infectious Diseases, 2007Co-Authors: Surapee Anantapreecha, Atchareeya Anuegoonpipat, Songthum Prakrong, Sumalee Chanama, Areerat Sangasang, Pathom Sawanpanyalert, Ichiro KuraneAbstract:Acute and convalescent plasma samples were obtained from 101 confirmed primary Dengue cases: 48 cases infected with Dengue Virus type 1, 10 cases with type 2, 42 cases with type 3 and one case with type 4. The hemagglutination inhibition (HI) titers of individual samples were at levels similar to each of the 4 Dengue Viruses at both the acute and convalescent stages, irrespective of the Dengue Virus that infected the patients. The results indicate that HI antibodies to Dengue Viruses are cross-reactive. When an HI test is used as a diagnostic test for Dengue Virus infection, the cross-reactive nature needs to be considered when interpreting the results.
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serotype cross reactive immunoglobulin m responses in Dengue Virus infections determined by enzyme linked immunosorbent assay
Clinical and Vaccine Immunology, 2000Co-Authors: Masaru Nawa, Tomohiko Takasaki, Kenichiro Yamada, Toshitaka Akatsuka, Ichiro KuraneAbstract:We developed immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assays (ELISAs) with four monovalent Dengue Virus antigens. We attempted to determine whether IgM responses in Dengue Virus infections are serotype specific or serotype cross-reactive. Serum samples from 14 confirmed Dengue cases were examined. In these 14 cases, which consisted of 12 Japanese and 2 non-Japanese patients, infecting Dengue Virus serotypes were defined by reverse transcription-PCR. Thirteen of the 14 cases were IgM positive in ELISA. IgM responses were serotype cross-reactive in these 13 cases but were highest against infecting Dengue Virus serotype in 9 of the 13 cases. These results indicate that IgM responses are generally Dengue serotype cross-reactive but that IgM levels are highest against the infecting serotype in most Dengue cases.
Eva Harris - One of the best experts on this subject based on the ideXlab platform.
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Mouse STAT2 Restricts Early Dengue Virus Replication
Cell host & microbe, 2010Co-Authors: Joseph Ashour, Eva Harris, Juliet Morrison, Maudry Laurent-rolle, Alan Belicha-villanueva, Courtney R. Plumlee, Dabeiba Bernal-rubio, Katherine L. Williams, Ana Fernandez-sesma, Christian SchindlerAbstract:Dengue Virus encodes several interferon antagonists. Among these the NS5 protein binds STAT2, a necessary component of the type I interferon signaling pathway, and targets it for degradation. We now demonstrate that the ability of Dengue NS5 to associate with and degrade STAT2 is species specific. Thus, NS5 is able to bind and degrade human STAT2, but not mouse STAT2. This difference was exploited to demonstrate, absent manipulation of the viral genome, that NS5-mediated IFN antagonism is essential for efficient Virus replication. Moreover, we demonstrate that differences in NS5 mediated binding and degradation between human and mouse STAT2 maps to a region within the STAT2 coiled-coil domain. By using STAT2(-/-) mice, we also demonstrate that mouse STAT2 restricts early Dengue Virus replication in vivo. These results suggest that overcoming this restriction through transgenic mouse technology may help in the development of a long-sought immune-competent mouse model of Dengue Virus infection.
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dermal type macrophages expressing cd209 dc sign show inherent resistance to Dengue Virus growth
PLOS Neglected Tropical Diseases, 2008Co-Authors: Winghong Kwan, Eva Harris, Erika Navarrosanchez, Helene Dumortier, Marion Decossas, Hortense Vachon, Flavia Barreto Dos Santos, Herve Fridman, Felix A Rey, Philippe DespresAbstract:Background: An important question in Dengue pathogenesis is the identity of immune cells involved in the control of Dengue Virus infection at the site of the mosquito bite. There is evidence that infection of immature myeloid dendritic cells plays a crucial role in Dengue pathogenesis and that the interaction of the viral envelope E glycoprotein with CD209/DCSIGN is a key element for their productive infection. Dermal macrophages express CD209, yet little is known about their role in Dengue Virus infection. Methods and Findings: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by Dengue Virus. The macrophages were able to internalize the Virus, but progeny Virus production was undetectable in the infected cells. In addition, no IFN-a was produced in response to the Virus. The inability of Dengue Virus to grow in the macrophages was attributable to accumulation of internalized Virus particles into poorly-acidified phagosomes. Conclusions: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped Virus and may constitute a prime defense system to prevent Dengue Virus spread shortly after the bite of the infected mosquito.
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y box binding protein 1 binds to the Dengue Virus 3 untranslated region and mediates antiviral effects
Journal of Biological Chemistry, 2007Co-Authors: Shruti M Paranjape, Eva HarrisAbstract:Abstract Dengue Virus, a member of the family Flaviviridae, poses a serious public health threat worldwide. Dengue Virus is a positive-sense RNA Virus that harbors a genome of ∼10.7 kb. Replication of Dengue Virus is mediated coordinately by cis-acting genomic sequences, viral proteins, and host cell factors. We have isolated and identified several host cell factors from baby hamster kidney cell extracts that bind with high specificity and high affinity to sequences within the untranslated regions of the Dengue Virus genome. Among the factors identified, Y box-binding protein-1 (YB-1) and the heterogeneous nuclear ribonucleoproteins (hnRNPs), hnRNP A1, hnRNP A2/B1, and hnRNP Q, bind to the Dengue Virus 3′-untranslated region. Further analysis indicated that YB-1 binds to the Dengue Virus 3′ stem loop, a conserved structural feature located at the 3′ terminus of the 3′-untranslated region of many flaviViruses. Analysis of the impact of YB-1 on replication of Dengue Virus in YB-1+/+ and YB-1–/– mouse embryo fibroblasts indicated that host YB-1 mediates an antiviral effect. Further studies demonstrated that this antiviral impact is due, at least in part, to a repressive role of YB-1 on Dengue Virus translation via a mechanism that requires viral genomic sequences. These results suggest a novel role for YB-1 as an antiviral host cell factor.
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Y box-binding protein-1 binds to the Dengue Virus 3'-untranslated region and mediates antiviral effects.
The Journal of biological chemistry, 2007Co-Authors: Shruti M Paranjape, Eva HarrisAbstract:Dengue Virus, a member of the family Flaviviridae, poses a serious public health threat worldwide. Dengue Virus is a positive-sense RNA Virus that harbors a genome of approximately 10.7 kb. Replication of Dengue Virus is mediated coordinately by cis-acting genomic sequences, viral proteins, and host cell factors. We have isolated and identified several host cell factors from baby hamster kidney cell extracts that bind with high specificity and high affinity to sequences within the untranslated regions of the Dengue Virus genome. Among the factors identified, Y box-binding protein-1 (YB-1) and the heterogeneous nuclear ribonucleoproteins (hnRNPs), hnRNP A1, hnRNP A2/B1, and hnRNP Q, bind to the Dengue Virus 3'-untranslated region. Further analysis indicated that YB-1 binds to the Dengue Virus 3' stem loop, a conserved structural feature located at the 3' terminus of the 3'-untranslated region of many flaviViruses. Analysis of the impact of YB-1 on replication of Dengue Virus in YB-1+/+ and YB-1-/- mouse embryo fibroblasts indicated that host YB-1 mediates an antiviral effect. Further studies demonstrated that this antiviral impact is due, at least in part, to a repressive role of YB-1 on Dengue Virus translation via a mechanism that requires viral genomic sequences. These results suggest a novel role for YB-1 as an antiviral host cell factor.
Alan L Rothman - One of the best experts on this subject based on the ideXlab platform.
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intracellular cytokine production by Dengue Virus specific t cells correlates with subclinical secondary infection
The Journal of Infectious Diseases, 2011Co-Authors: Steven C Hatch, Timothy P Endy, Daniel H Libraty, Stephen J Thomas, Anuja Mathew, James A Potts, Pamela P Pazoles, Robert V Gibbons, Alan L RothmanAbstract:The pathophysiology of Dengue Virus infection remains poorly understood, although secondary infection is strongly associated with more severe disease. In the present study, we performed a nested, case-control study comparing the responses of pre-illness peripheral blood mononuclear cells between children who would subsequently develop either subclinical or symptomatic secondary infection 6–11 months after the baseline blood samples were obtained and frozen. We analyzed intracellular cytokine production by CD4+ and CD8+ cells in response to stimulation with Dengue antigen. We found higher frequencies of Dengue Virus–specific TNFα, IFNγ-, and IL-2–producing T cells among schoolchildren who subsequently developed subclinical infection, compared with those who developed symptomatic secondary Dengue Virus infection. Although other studies have correlated immune responses during secondary infection with severity of disease, to our knowledge this is the first study to demonstrate a pre-infection Dengue-specific immune response that correlates specifically with a subclinical secondary infection.
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spatial and temporal circulation of Dengue Virus serotypes a prospective study of primary school children in kamphaeng phet thailand
American Journal of Epidemiology, 2002Co-Authors: Timothy P Endy, David W Vaughn, Ananda Nisalak, Supamit Chunsuttiwat, Daniel H Libraty, Sharone Green, Alan L Rothman, Francis A EnnisAbstract:Dengue Virus occurs as four distinct serotypes, each of which causes epidemics throughout the tropical and subtropical regions of the world. Few studies have examined co-circulation of multiple Dengue Virus serotypes in a well-defined cohort population over time and their capacity to produce severe Dengue disease. In this paper, the authors report the details and findings of the first 3 years (1998-2000) of an ongoing prospective study of Dengue Virus transmission and disease severity in a cohort of children in northern Thailand. A total of 108 Dengue Virus isolates were obtained from 167 acute Dengue Virus infections; 23% were DEN-1, 35% were DEN-2, 41% were DEN-3, and 1 % were DEN-4. Despite the proximity of the schools, there was marked spatial and temporal clustering of transmission of each Dengue serotype. Serotype-specific antibody levels prior to the Dengue transmission season were not predictive of the incidence of Dengue Virus infections or the predominant serotype transmitted at individual schools. All Dengue serotypes produced severe Dengue illness, although DEN-3 produced more severe symptoms than the other Dengue serotypes. The authors' findings emphasize the complexity of Dengue serotype-specific Virus transmission and severe Dengue disease and have important implications for Dengue control and vaccine development.
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epidemiology of inapparent and symptomatic acute Dengue Virus infection a prospective study of primary school children in kamphaeng phet thailand
American Journal of Epidemiology, 2002Co-Authors: Timothy P Endy, David W Vaughn, Ananda Nisalak, Supamit Chunsuttiwat, Daniel H Libraty, Sharone Green, Alan L Rothman, Francis A EnnisAbstract:Dengue Viruses are a major cause of morbidity in tropical and subtropical regions of the world. Knowledge about the epidemiology and host determinants of inapparent and severe Dengue Virus infections is limited. In this paper, the authors report findings from the first 3 years of a prospective study of Dengue Virus transmission and disease severity conducted in a cohort of 2,119 elementary school children in northern Thailand. A total of 717,106 person-school days were observed from 1998 to 2000. The incidence of inapparent and of symptomatic Dengue Virus infection was 4.3% and 3.6% in 1998, 3.2% and 3.3% in 1999, and 1.4% and 0.8% in 2000, respectively. Symptomatic Dengue Virus infection was responsible for 3.2%, 7.1%, and 1.1% of acute-illness school absences in 1998, 1999, and 2000, respectively. The early symptom complex of acute Dengue Virus infection is protean and difficult to distinguish from other causes of febrile childhood illnesses. The authors' results illustrate the spatial and temporal diversity of Dengue Virus infection and the burden of Dengue disease in schoolchildren in Thailand. Their findings increase understanding of Dengue Virus transmission and disease severity in a well-defined cohort population and offer a study design in which to test the efficacy of potential Dengue vaccines.
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bystander target cell lysis and cytokine production by Dengue Virus specific human cd4 cytotoxic t lymphocyte clones
Journal of Virology, 1999Co-Authors: Susan J Gagnon, Francis A Ennis, Alan L RothmanAbstract:Dengue hemorrhagic fever, the severe form of Dengue Virus infection, is believed to be an immunopathological response to a secondary infection with a heterologous serotype of Dengue Virus. Dengue Virus capsid protein-specific CD4(+) cytotoxic T-lymphocyte (CTL) clones were shown to be capable of mediating bystander lysis of non-antigen-presenting target cells. After activation by anti-CD3 or in the presence of unlabeled antigen-presenting target cells, these clones could lyse both Jurkat cells and HepG2 cells as bystander targets. Lysis of HepG2 cells suggests a potential role for CD4(+) CTL in the liver involvement observed during Dengue Virus infection. Three CD4(+) CTL clones were demonstrated to lyse cognate, antigen-presenting target cells by a mechanism that primarily involves perforin, while bystander lysis occurred through Fas/Fas ligand interactions. In contrast, one clone used a Fas/Fas ligand mechanism to lyse both cognate and bystander targets. Cytokine production by the CTL clones was also examined. In response to stimulation with D2 antigen, CD4(+) T-cell clones produced gamma interferon, tumor necrosis factor alpha (TNF-alpha) and TNF-beta. The data suggest that CD4(+) CTL clones may contribute to the immunopathology observed upon secondary Dengue Virus infections through direct cytolysis and/or cytokine production.