Medicine and Health Sciences Commons^™

In Silico Analysis Of C-Type Lectins As Co-Infection Receptors Of Dengue And Chikungunya Viruses In Aedes Aegypti, Munawir Sazali, R. C. Hidayat Soesilohadi, Nastiti Wijayanti, Tri Wibawa, Arif Nur Muhammad Ansori

Makara Journal of Science

Aedes aegypti is a primer vector of dengue virus (DENV) and chikungunya virus (CHIKV). The susceptibility of mosquitoes to DENV and CHIKV depends on their recognition receptor of pathogens. C-type lectins (CTLs) are an important mediator of virus infection in A. aegypti. This study aims to identify potential receptors and determine the binding affinity between ligand–receptor interaction, CTLs and virus envelopes (DENV-1, 2, 3, and 4 and CHIKV) interaction based on in silico analysis. Sample sequences were obtained from GenBank (NCBI), and 10 CTLs were acquired from VectorBase. Homology modeling based on a minimum standard of 20% was processed …

Transcriptional And Translational Dynamics Of Zika And Dengue Virus Infection., Kamini Singh, Maria Guadalupe Martinez, Jianan Lin, James Gregory, Trang Uyen Nguyen, Rawan Abdelaal, Kristy Kang, Kristen Brennand, Arnold Grünweller, Zhengqing Ouyang, Hemali Phatnani, Margaret Kielian, Hans-Guido Wendel

Faculty Research 2022

Zika virus (ZIKV) and dengue virus (DENV) are members of the Flaviviridae family of RNA viruses and cause severe disease in humans. ZIKV and DENV share over 90% of their genome sequences, however, the clinical features of Zika and dengue infections are very different reflecting tropism and cellular effects. Here, we used simultaneous RNA sequencing and ribosome footprinting to define the transcriptional and translational dynamics of ZIKV and DENV infection in human neuronal progenitor cells (hNPCs). The gene expression data showed induction of aminoacyl tRNA synthetases (ARS) and the translation activating PIM1 kinase, indicating an increase in RNA translation capacity. …

The Clinical Features Of Co-Circulating Dengue Viruses And The Absence Of Dengue Hemorrhagic Fever In Pakistan, Erum Khan, Dhani Prakoso, Kehkashan Imtiaz, Faisal Malik, Joveria Farooqi, Maureen T. Long, Kelli L. Barr

Department of Pathology and Laboratory Medicine

Dengue virus (DENV) is the most common and widespread arboviral infection worldwide. Though all four DENV serotypes cocirculate in nature, the clinicopathological framework of these serotypes is undefined in Pakistan. A cross-sectional, observational study was performed to document the circulation of various arboviruses in the Sindh region of Pakistan. Here we describe a population of patients diagnosed with DENV spanning a 2-year period. This study used an orthogonal system of NS1 antigen ELISA followed by RT-PCR for DENV detection and subtyping. A total of 168 NS1 positive patients were evaluated of which 91 patients were serotyped via RT-PCR. There was …

A Case-Study Approach To Investigate Transmission, Co-Infection, And Clinical Sequelae During Epidemics Of Dengue And Ebola Virus Disease, Jennifer Elizabeth Giovanni

LSU Doctoral Dissertations

From within their ecologic niches, zoonotic viruses emerge from animal reservoirs into the edges and centers of human habitation to exploit opportunities for unabated transmission within immunologically–naïve populations. Our understanding of where, in whom, and how these viruses emerge is under direct challenge, driving the evolution of modern infectious disease epidemiology within a rapidly-connected global community. The studies presented herein are based on analyses of both aggregate and case-level data, which, we argue, provide unique insight into the complexities of transmission, co-infection, and clinical sequelae occurring within, and arising from, epidemics of emerging zoonotic viruses. In Chapter II, we investigate …

Real-Time Dengue Forecasting In Thailand: A Comparison Of Penalized Regression Approaches Using Internet Search Data, Caroline Kusiak

Masters Theses

Dengue fever affects over 390 million people annually worldwide and is of particu- lar concern in Southeast Asia where it is one of the leading causes of hospitalization. Modeling trends in dengue occurrence can provide valuable information to Public Health officials, however many challenges arise depending on the data available. In Thailand, reporting of dengue cases is often delayed by more than 6 weeks, and a small fraction of cases may not be reported until over 11 months after they occurred. This study shows that incorporating data on Google Search trends can improve dis- ease predictions in settings with severely …

Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy

Dissertations, Theses, and Capstone Projects

Dengue, the most rapidly spreading flavivirus, threatens to affect almost half of the human global population. We previously showed that dengue-2 protects canine kidney cells (MDCK) from cytotoxic chemicals. We showed, independently, that cell protection, as well as viral replication and maturation, are positively regulated by PI3K-dependent autophagy. However, we had not identified the specific pathway that induces autophagy in infected cells. The current study explores the role of a specific branch of the endoplasmic reticulum (ER) stress-mediated Unfolded Protein Response (UPR), the PERK/eIF2α/ATF4 pathway in the induction of autophagy by …

Role Of Tnf Α, Il-6 And Cxcl10 In Dengue Disease Severity, Kiran I. Masood, Bushra Jamil, Maryam Rahim, Muniba Islam, Muhammad Farhan, Zahra Hasan

Department of Pathology and Laboratory Medicine

Background and objective: Dengue virus infections (Dengue) have become increasingly common in Pakistan and can result in case fatalities if not managed appropriately. Patients with Dengue virus infection may be asymptomatic or present with Dengue fever (DF), Dengue with warning signs (DWS) or severe Dengue (SD). Severity in Dengue is coincident with an exacerbated production of lymphocyte-induced cytokines and chemokines which are associated with plasma leakage. We investigated the association of circulating levels of cytokines such as Interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and CXCL-10 in Dengue patients with differing severity of disease.
Material and methods: Dengue infection was confirmed …

Arthropod Evs Mediate Dengue Virus Transmission Through Interaction With A Tetraspanin Domain Containing Glycoprotein Tsp29fb, Ashish Vora, Wenshuo Zhou, Berlin Londono-Renteria, Michael Woodson, Michael B. Sherman, Tonya M. Collpitts, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Dengue virus (DENV) is a mosquito-borne flavivirus that causes dengue fever in humans, worldwide. Using in vitro cell lines derived from Aedes albopictus and Aedes aegypti, the primary vectors of DENV, we report that DENV2/DENV3-infected cells secrete extracellular vesicles (EVs), including exosomes, containing infectious viral RNA and proteins. A full-length DENV2 genome, detected in arthropod EVs, was infectious to naïve mosquito and mammalian cells, including human-skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed mosquito EVs with a size range from 30 to 250 nm. Treatments with RNase A, Triton X-100, and 4G2 antibody-bead binding assays showed that infectious …

Evaluation Of A Microsphere-Based Immunoassay (Mia) In Measuring Diagnostic And Prognostic Markers Of Dengue Virus Infection, Jason H. Ambrose

USF Tampa Graduate Theses and Dissertations

Infections with dengue viruses (DENV) constitute both a global problem as well as locally in Florida. DENV comprise four distinct serotypes of single-stranded RNA viruses and belong to the family Flaviviridae. DENV are among the most medically important arboviruses in the world and cases may currently exceed 400 million per annum. Additionally, dengue established its first recorded endemic transmission cycle in the state of Florida in over a half century, first within the Florida Keys during 2009-10 followed by an unrelated outbreak in Martin County in 2013. The clinical profile of DENV infections ranges from a mild febrile illness …

Rapid Diagnosis Of Dengue Viremia By Reverse Transcriptase-Polymerase Chain Reaction Using 3'-Noncoding Region Universal Primers, T. Mirawati Sudiro, Hiroaki Ishiko, Sharone Green, Ananda Nisalak, David W. Vaughn, Siripen Kalayanarooj, Alan L. Rothman, Boonyos Raengsakulrach, Jurand Janus, Ichiro Kurane, Francis A. Ennis

Sharone Green

A reverse transcriptase-polymerase chain reaction (RT-PCR) method was developed as a rapid diagnostic test of dengue viremia. To detect dengue viruses in serum or plasma specimens, a pair of universal primers was designed for use in the RT-PCR. Using these primers, the 3'-noncoding region of dengue virus types 1, 2, 3, and 4 could be amplified, but not those of other flaviviruses, such as West Nile virus, Japanese encephalitis virus, and yellow fever virus, or the alphavirus Sindbis virus. The sensitivity of the RT-PCR assay was similar to that of a quantitative fluorescent focus assay of dengue viruses in cell …

Life-Shortening Wolbachia Infection Reduces Population Growth Of Aedes Aegypti, Eunho Suh, David R. Mercer, Stephen L. Dobson

Entomology Faculty Publications

Wolbachia bacteria are being introduced into natural populations of vector mosquitoes, with the goal of reducing the transmission of human diseases such as Zika and dengue fever. The successful establishment of Wolbachia infection is largely dependent on the effects of Wolbachia infection to host fitness, but the effects of Wolbachia infection on the individual life-history traits of immature mosquitoes can vary. Here, the effects of life-shortening Wolbachia (wMelPop) on population growth of infected individuals were evaluated by measuring larval survival, developmental time and adult size of Aedes aegypti in intra- (infected or uninfected only) and inter-group (mixed with …

Hla Class I Supertype Associations With Clinical Outcome Of Secondary Dengue Virus Infections In Ethnic Thais, Sasijit Vejbaesya, Rungrot Thongpradit, Siripen Kalayanarooj, Komon Luangtrakool, Panpimon Luangtrakool, Robert V. Gibbons, Duangporn Srinak, Somporn Ngammthaworn, Kusuma Apisawes, In-Kyu Yoon, Stephen J. Thomas, Richard G. Jarman, Anon Srikiatkhachorn, Sharone Green, Dasnayanee Chandanayingyong, Sangshin Park, Jennifer Friedman, Alan L. Rothman, Henry A.F. Stephens

Sharone Green

BACKGROUND: Human leukocyte antigen (HLA) supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system.

OBJECTIVES: To analyze HLA class I supertype associations with clinical outcome in hospitalized Thai children with acute dengue illness.

METHODS: Seven hundred sixty-two patients and population-matched controls recruited predominantly in Bangkok were HLA-A and -B typed. HLA supertype frequencies were compared and tested for significant dengue disease associations using logistic regression analyses. Multivariable models were built by conducting forward stepwise selection procedures.

RESULTS: In the final logistic regression model, the HLA-B44 supertype was protective against dengue hemorrhagic fever (DHF) …

The Emergence Of The Zika, Chikungunya, And Dengue Viruses In Brazil, The Dominican Republic, And Puerto Rico, Nelson Xavier Del Pilar

Honors Scholar Theses

The Zika, Chikungunya, and Dengue viruses are three emerging viral infections of the 21st century. Outbreaks have occurred in twenty countries, including areas of South America, and territories in the Caribbean. These viral diseases are mosquito-borne infections transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes. The origins of the diseases, viral morphology, and vector transmission will be described in this review as well as symptoms that humans experience, medical testing procedures, and preventative measures. This study will focus on three locations: Brazil, the Dominican Republic, and Puerto Rico. There are many similarities between the three viruses to emphasize, but …

Viral Replication And Paracrine Effects Result In Distinct, Functional Responses Of Dendritic Cells Following Infection With Dengue 2 Virus, Zachary Nightingale, Chinmay Patkar, Alan Rothman

Alan Rothman

Dengue virus (DENV), a re-emerging arbovirus, readily infects dendritic cells (DC) in culture and in vivo. However, there have been contradictory reports regarding the effect of DENV infection on DC activation and maturation. DC undergo a series of functional changes following exposure to infectious agents, including cytokine production and costimulatory and MHC molecule induction, culminating in stimulation of adaptive immune responses. Immunological memory to primary DENV infection critically influences disease severity during subsequent infections with heterologous serotypes. To explore these phenomena, we examined DENV infection-dependent and -independent effects on DC secretory, phenotypic, and allostimulatory functions. DENV infection of DC resulted …

Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman

Alan Rothman

Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by …

Intracellular Cytokine Production By Dengue Virus-Specific T Cells Correlates With Subclinical Secondary Infection, Steven Hatch, Timothy Endy, Stephen Thomas, Anuja Mathew, James Potts, Pamela Pazoles, Daniel Libraty, Robert Gibbons, Alan Rothman

Alan Rothman

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 TNFalpha, IFNgamma-, and IL-2-producing T cells among schoolchildren who subsequently developed subclinical infection, compared with …

T Cell Responses To An Hla-B*07-Restricted Epitope On The Dengue Ns3 Protein Correlate With Disease Severity, Iva Zivna, Sharone Green, David Vaughn, Siripen Kalayanarooj, Henry Stephens, Dasnayanee Chandanayingyong, Ananda Nisalak, Francis Ennis, Alan Rothman

Alan Rothman

Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221-232 of the DV NS3 protein, in 10 HLA-B*07(+) Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects. The frequency of peptide-specific T cells was higher in subjects who had experienced DHF …

Dengue: Defining Protective Versus Pathologic Immunity, Alan Rothman

Alan Rothman

Dengue is an expanding public health problem, and an effective vaccine remains elusive. This review discusses how the significant influence of sequential infection with different dengue virus serotypes on the severity of disease can be viewed in terms of beneficial and detrimental effects of heterologous immunity. A more complete understanding of these effects is likely to be critical for predicting optimal vaccine-induced immune responses.

Dengue Virus Nonstructural Protein Ns5 Induces Interleukin-8 Transcription And Secretion, Carey L. Medin, Katherine A. Fitzgerald, Alan L. Rothman

Alan Rothman

Elevated circulating levels of chemokines have been reported in patients with dengue fever and are proposed to contribute to the pathogenesis of dengue disease. To establish in vitro models for chemokine induction by dengue 2 virus (DEN2V), we studied a variety of human cell lines and primary cells. DEN2V infection of HepG2 and primary dendritic cells induced the production of interleukin-8 (IL-8), RANTES, MIP-1alpha, and MIP-1beta, whereas only IL-8 and RANTES were induced following dengue virus infection of HEK293 cells. Chemokine secretion was accompanied by an increase in steady-state mRNA levels. No chemokine induction was observed in HEK293 cells treated …

Determinants Of Inapparent And Symptomatic Dengue Infection In A Prospective Study Of Primary School Children In Kamphaeng Phet, Thailand, Timothy Endy, Kathryn Anderson, Ananda Nisalak, In-Kyu Yoon, Sharone Green, Alan Rothman, Stephen Thomas, Richard Jarman, Daniel Libraty, Robert Gibbons

Alan Rothman

BACKGROUND: Dengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Inapparent dengue is an important component of the overall burden of dengue infection. It provides a source of infection for mosquito transmission during the course of an epidemic, yet by definition is undetected by health care providers. Previous studies of inapparent or subclinical infection have reported varying ratios of symptomatic to inapparent dengue infection.

METHODOLOGY/PRINCIPAL FINDINGS: In a prospective study of school children in Northern Thailand, we describe the spatial and temporal variation of the symptomatic to inapparent (S:I) dengue illness ratio. Our …

T Cell Receptor Vbeta Gene Usage In Thai Children With Dengue Virus Infection, Susan Gagnon, Anita Leporati, Sharone Green, Siripen Kalayanarooj, David Vaughn, Henry Stephens, Saroj Suntayakorn, Ichiro Kurane, Francis Ennis, Alan Rothman

Alan Rothman

T lymphocyte activation during dengue is thought to contribute to the pathogenesis of dengue hemorrhagic fever (DHF). We examined the T cell receptor Vbeta gene usage by a reverse transcriptase-polymerase chain reaction assay during infection and after recovery in 13 children with DHF and 13 children with dengue fever (DF). There was no deletion of specific Vbeta gene families. We detected significant expansions in usage of single Vbeta families in six subjects with DHF and three subjects with DF over the course of infection, but these did not show an association with clinical diagnosis, viral serotype, or HLA alleles. Differences …

Virus-Induced Decline In Soluble Vascular Endothelial Growth Receptor 2 Is Associated With Plasma Leakage In Dengue Hemorrhagic Fever, Anon Srikiatkhachorn, Chuanpis Ajariyakhajorn, Timothy Endy, Siripen Kalayanarooj, Daniel Libraty, Sharone Green, Francis Ennis, Alan Rothman

Alan Rothman

Some individuals infected with dengue virus develop dengue hemorrhagic fever (DHF), a viral hemorrhagic disease characterized by a transient period of localized plasma leakage. To determine the importance of vascular endothelial growth factor A (VEGF-A) in this syndrome, we compared plasma levels of VEGF-A and the soluble forms of its receptors in patients with DHF to patients with dengue fever (DF), a milder form of dengue virus infection without plasma leakage. We observed a rise in the plasma levels of free, but not total VEGF-A in DHF patients at the time of plasma leakage. This was associated with a decline …

Cell Type-Specific Mechanisms Of Interleukin-8 Induction By Dengue Virus And Differential Response To Drug Treatment, Carey Medin, Alan Rothman

Alan Rothman

In vitro infection with dengue virus induces interleukin (IL)-8 secretion, which increases endothelial cell permeability; this has been proposed as a mechanism for plasma leakage in dengue hemorrhagic fever. We studied the mechanisms of IL-8 induction, using luciferase reporter constructs, and the effect of pharmacological inhibitors of either IL-8 secretion or nuclear factor- kappa B (NF-kappa B) activation on IL-8 induction by dengue 2 virus (DEN2V) infection. IL-8 induction by DEN2V infection was associated with activation of NF- kappa B and activator protein-1 (AP-1) in HEK293A cells but only with activation of AP-1 in HepG2 cells. Treatment with SB203580, a …

Dengue Virus Induces Novel Changes In Gene Expression Of Human Umbilical Vein Endothelial Cells, Rajas Warke, Kris Xhaja, Katherine Martin, Marcia Fournier, Sunil Shaw, Nathaly Brizuela, Norma De Bosch, David Lapointe, Francis Ennis, Alan Rothman, Irene Bosch

Alan Rothman

Endothelial cells are permissive to dengue virus (DV) infection in vitro, although their importance as targets of DV infection in vivo remains a subject of debate. To analyze the virus-host interaction, we studied the effect of DV infection on gene expression in human umbilical vein endothelial cells (HUVECs) by using differential display reverse transcription-PCR (DD-RTPCR), quantitative RT-PCR, and Affymetrix oligonucleotide microarrays. DD identified eight differentially expressed cDNAs, including inhibitor of apoptosis-1, 2'-5' oligoadenylate synthetase (OAS), a 2'-5' OAS-like (OASL) gene, galectin-9, myxovirus protein A (MxA), regulator of G-protein signaling, endothelial and smooth muscle cell-derived neuropilin-like protein, and phospholipid scramblase 1. …

Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman

Alan Rothman

We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA …

B-Cell Responses During Primary And Secondary Dengue Virus Infections In Humans, Anuja Mathew, Kim West, Siripen Kalayanarooj, Robert Gibbons, Anon Srikiatkhachorn, Sharone Green, Daniel Libraty, Smita Jaiswal, Alan Rothman

Alan Rothman

Low-avidity serotype-cross-reactive antibodies are hypothesized to play a key role in triggering severe disease in patients with secondary dengue virus (DENV) infection. However, there is little systematic information about the frequency, avidity, and cross-reactivity of DENV-specific B cells in individuals experiencing primary instead of secondary infection. We compared DENV-specific B-cell responses in a cohort of Thai children with primary or secondary DENV infection. B cells specific for DENV precursor membrane protein, envelope (E) protein, and nonstructural protein 1 were detectable in immune peripheral blood mononuclear cells with the highest frequencies of DENV E-specific B cells detected in patients experiencing primary …

Immunopathologic Mechanisms Of Dengue Hemorrhagic Fever And Dengue Shock Syndrome, Ichiro Kurane, Alan Rothman, Peter Livingston, Sharone Green, Susan Gagnon, Jurand Janus, Bruce Innis, Suchitra Nimmannitya, Ananda Nisalak, Francis Ennis

Alan Rothman

Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas of the world. The immunopathological mechanisms that result in severe complications of dengue virus infection, i.e. dengue hemorrhagic fever (DHF), are important to determine. Primary dengue virus infections induce serotype-specific and serotype-cross-reactive, CD4+ and CD8+ memory cytotoxic T lymphocytes (CTL). In secondary infections with a virus of a different serotype from that which caused primary infections, the presence of cross-reactive non-neutralizing antibodies results in an increased number of infected monocytes by dengue virus--antibody complexes. This in turn results in marked activation of serotype cross-reactive …

Elevated Levels Of Soluble St2 Protein In Dengue Virus Infected Patients, Aniuska Becerra, Rajas Warke, Norma De Bosch, Alan Rothman, Irene Bosch

Alan Rothman

Levels of the soluble form of the interleukin-1 receptor-like 1 protein (IL-1RL-1/ST2) are elevated in the serum of patients with diseases characterized by an inflammatory response. The objective of this study was to determine the concentration of soluble ST2 (sST2) in dengue infected patients during the course of the disease. Twenty-four patients with confirmed dengue infection, classified as dengue fever, and 11 patients with other febrile illness (OFI) were evaluated. Levels of sST2 in serum and laboratory variables usually altered during dengue infections were measured. Dengue infected patients had higher serum sST2 levels than OFI at the end of the …

Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman

Sharone Green

Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by …

T Cell Responses To An Hla-B*07-Restricted Epitope On The Dengue Ns3 Protein Correlate With Disease Severity, Iva Zivna, Sharone Green, David Vaughn, Siripen Kalayanarooj, Henry Stephens, Dasnayanee Chandanayingyong, Ananda Nisalak, Francis Ennis, Alan Rothman

Sharone Green

Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221-232 of the DV NS3 protein, in 10 HLA-B*07(+) Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects. The frequency of peptide-specific T cells was higher in subjects who had experienced DHF …