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At least 1,243 records · Page 69Linked to original sources
PubMed1998

Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection.

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 B57 restricted, and the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221 to 232 on NS3. These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive.

CD4-Positive T-Lymphocytes↗
PubMed2002

Derivation and characterization of a dengue type 1 host range-restricted mutant virus that is attenuated and highly immunogenic in monkeys.

We recently described the derivation of a dengue serotype 2 virus (DEN2mutF) that exhibited a host range-restricted phenotype; it was severely impaired for replication in cultured mosquito cells (C6/36 cells). DEN2mutF virus had selected mutations in genomic sequences predicted to form a 3' stem-loop structure (3'-SL) that is conserved among all flavivirus species. The 3'-SL constitutes the downstream terminal similar95 nucleotides of the 3' noncoding region in flavivirus RNA. Here we report the introduction of these same mutational changes into the analogous region of an infectious DNA derived from the genome of a human-virulent dengue serotype 1 virus (DEN1), strain Western Pacific (DEN1WP). The resulting DEN1 mutant (DEN1mutF) exhibited a host range-restricted phenotype similar to that of DEN2mutF virus. DEN1mutF virus was attenuated in a monkey model for dengue infection in which viremia is taken as a correlate of human virulence. In spite of the markedly reduced levels of viremia that it induced in monkeys compared to DEN1WP, DEN1mutF was highly immunogenic. In addition, DEN1mutF-immunized monkeys retained high levels of neutralizing antibodies in serum and were protected from challenge with high doses of the DEN1WP parent for as long as 17 months after the single immunizing dose. Phenotypic revertants of DEN1mutF and DEN2mutF were each detected after a total of 24 days in C6/36 cell cultures. Complete nucleotide sequence analysis of DEN1mutF RNA and that of a revertant virus, DEN1mutFRev, revealed that (i) the DEN1mutF genome contained no additional mutations upstream from the 3'-SL compared to the DEN1WP parent genome and (ii) the DEN1mutFRev genome contained de novo mutations, consistent with our previous hypothesis that the defect in DEN2mutF replication in C6/36 cells was at the level of RNA replication. A strategy for the development of a tetravalent dengue vaccine is discussed.

Animals↗
PubMed2002

Dengue type 3 virus in plasma is a population of closely related genomes: quasispecies.

Using reverse transcription-PCR and clonal sequencing of the dengue virus envelope gene derived from the plasma samples of six patients, we reported for the first time that dengue virus circulates as a population of closely related genomes. The extent of sequence diversity varied among patients, with the mean pairwise proportions of difference ranging from 0.21 to 1.67%. Genome-defective viruses were found in 5.8% of the total number of clones analyzed. Our findings on the quasispecies nature of dengue virus and the defective virus in vivo have implications with regard to the pathogenesis of dengue virus.

Amino Acid Sequence↗
PubMed2003

Diverse dengue type 2 virus populations contain recombinant and both parental viruses in a single mosquito host.

Envelope (E) protein genes sampled from populations of dengue 2 (DEN-2) virus in individual Aedes aegypti mosquitoes and in serum from dengue patients were copied to cDNA, cloned, and sequenced. The nucleotide sequences of the E genes in more than 70% of the clones differed from the consensus sequence for the corresponding virus population at up to 11 sites, and 24 of the 94 clones contained at least one stop codon. Virus populations recovered up to 2 years apart yielded clones with similar polymorphisms in the E gene. For one mosquito, the clones obtained fell into two genotypes. One group of sequences was closely related to those of viruses recovered from dengue patients in the same locality (Yangon, Myanmar) since 1995 and were classified as Asian 1 genotype. The second group were Cosmopolitan genotype viruses which were also circulating in Yangon in 2000 and which were related to DEN-2 viruses sampled from southern China in 1999. Finally, one clone was identified as a recombinant genome composed of portions of these two "parental" genotypes. This is the first report of recombinant and parental dengue viruses in a single host.

Aedes↗
PubMed2004

Identification of chimpanzee Fab fragments by repertoire cloning and production of a full-length humanized immunoglobulin G1 antibody that is highly efficient for neutralization of dengue type 4 virus.

A safe and effective dengue vaccine is still not available. Passive immunization with monoclonal antibodies from humans or nonhuman primates represents an attractive alternative for the prevention of dengue virus infection. Fab monoclonal antibodies to dengue type 4 virus (DENV-4) were recovered by repertoire cloning of bone marrow mRNAs from an immune chimpanzee and analyzed for antigen binding specificity, V(H) and V(L) sequences, and neutralizing activity against DENV-4 in vitro. Fabs 5A7, 3C1, 3E4, and 7G4 were isolated from a library constructed from a chimpanzee following intrahepatic transfection with infectious DENV-4 RNA. Fabs 5H2 and 5D9, which had nearly identical V(H) sequences but varied in their V(L) sequences, were recovered from a library constructed from the same chimpanzee after superinfection with a mixture of DENV-1, DENV-2, and DENV-3. In radioimmunoprecipitation, Fab 5A7 precipitated only DENV-4 prM, and Fabs 3E4, 7G4, 5D9, and 5H2 precipitated DENV-4 E but little or no prM. Fab 3E4 and Fab 7G4 competed with each other for binding to DENV-4 in an enzyme-linked immunosorbent assay, as did Fab 3C1 and Fab 5A7. Fab 5H2 recognized an epitope on DENV-4 that was separate from the epitope(s) recognized by other Fabs. Both Fab 5H2 and Fab 5D9 neutralized DENV-4 efficiently with a titer of 0.24 to 0.58 micro g/ml by plaque reduction neutralization test (PRNT), whereas DENV-4-neutralizing activity of other Fabs was low or not detected. Fab 5H2 was converted to full-length immunoglobulin G1 (IgG1) by combining it with human sequences. The humanized chimpanzee antibody IgG1 5H2 produced in CHO cells neutralized DENV-4 strains from different geographical origins at a similar 50% plaque reduction (PRNT(50)) titer of 0.03 to 0.05 micro g/ml. The DENV-4 binding affinities were 0.42 nM for Fab 5H2 and 0.24 nM for full-length IgG1 5H2. Monoclonal antibody IgG1 5H2 may prove valuable for passive immunoprophylaxis against dengue virus in humans.

Amino Acid Sequence↗
PubMed2005

Invasion and maintenance of dengue virus type 2 and type 4 in the Americas.

Dengue virus type 4 (DENV-4) was first reported in the Americas in 1981, where it caused epidemics of dengue fever throughout the region. In the same year, the region's first epidemic of dengue hemorrhagic fever was reported, caused by an Asian strain of dengue virus type 2 (DENV-2) that was distinct from the American subtype circulating previously. Despite the importance of these epidemics, little is known about the rates or determinants of viral spread among island and mainland populations or their directions of movement. We employed a Bayesian coalescent approach to investigate the transmission histories of DENV-2 and DENV-4 since their introduction in 1981 and a parsimony method to assess patterns of strain migration. For both viruses there was an initial invasion phase characterized by an exponential increase in the number of DENV lineages, after which levels of genetic diversity remained constant despite reported fluctuations in DENV-2 and DENV-4 activity. Strikingly, viral lineage numbers increased far more rapidly for DENV-4 than DENV-2, indicative of a more rapid rate of exponential population growth in DENV-4 or a higher rate of geographic dispersal, allowing this virus to move more effectively among localities. We propose that these contrasting dynamics may reflect underlying differences in patterns of host immunity. Despite continued gene flow along particular transmission routes, the overall extent of viral traffic was less than expected under panmixis. Hence, DENV in the Americas has a clear geographic structure that maintains viral diversity between outbreaks.

Americas↗
PubMed2005

[Early indicators of severity in dengue virus infection].

OBJECTIVE: To identify clinical markers of severity in dengue, different from those of major hemorrhage. DESIGN: Cross-sectional study. POPULATION AND METHODS: Patients with a diagnosis of dengue infection admitted to hospitals in Santander (Colombia) during the years 1993 to 1998 were studied. On admittance or during hospitalization, patients were classified as cases of dengue hemorrhagic fever (DHF) or dengue fever (DF). Clinical findings differing from those of major hemorrhage were recorded in the emergency room and during the first assessment at hospitalization. The association between these findings and the outcome of DHF were evaluated using univariate and multivariate analyses. RESULTS: 891 patients (DF: 420; DHF: 471) were included in the study. Associations were found between DHF and the following signs and symptoms: vomiting (OR: 1.89; 95% CI: 1.37-2.6; p = 0.0001); gingival hemorrhage (OR: 1.55; 95% CI: 1.11-2.18; p = 0.01); epistaxis (OR: 1.78; 95% CI: 1.28-2.48; p = 0.001); hepatomegaly (OR: 2.56; 95% CI: 1.61-4.07; p < 0.0001); microscopic hematuria (OR: 2.33; 95% CI: 1.36-4; p = 0.002); and rash (OR: 1.36; 95% CI: 1.04-1.77; p = 0.02). The hematocrit in the emergency room and on the first day of hospitalization was significantly higher in the group with DHF (p < 0.001, in both observations). On multivariate analysis, the hematocrit from DHF patients obtained in the emergency room was higher than that from DF, independently of the other relevant variables (difference: 3.65; 95% CI: 2.81-4.49). CONCLUSION: Under the study conditions, there was an association between early clinical findings and DHF. These results must be evaluated in a cohort study.

Adolescent↗
PubMed2006

[Evaluation of IgM determination in acute serum for the diagnosis of dengue in an endemic area].

Evaluation of IgM determination in acute serum for the diagnosis of dengue in an endemic area We evaluated the clinical usefulness of dengue IgM detection in acute serum using an ELISA test in 167 patients with dengue and 225 patients with acute febrile syndrome of another etiology. The sensitivity of the test was 29.9%, specificity was 99.1%, positive predictive value was 96.2%, and negative predictive value was 65.6%. Because of the test's high specificity and positive predictive value, a positive result could support a diagnosis of dengue in endemic areas with a high degree of certainty; a negative result would require complementary studies.

Antibodies, Viral↗
PubMed1994

Comparative analysis of NS3 sequences of temporally separated dengue 3 virus strains isolated from southeast Asia.

By a combination of PCR and direct-cycle sequencing using consensus primers, we analyzed approximately 400-bp fragments within the NS3 genes of twenty-one dengue virus type 3 strains isolated from five neighboring Southeast Asian countries at different time intervals from 1956 to 1992. The majority of base disparities were silent mutations, with few predicted amino acid substitutions, thus emphasizing the strict conservation of the NS3 gene. Phylogenetic trees constructed on the basis of these nucleotide differences revealed distinct but related clusters of strains from the Philippines, Indonesia, and strains from Singapore and Malaysia of the 1970s and early 1980s, while the Thai cluster was relatively more distant. This genetic relationship was compatible with that proposed by other workers who have studied other dengue 3 virus genes such as E, M and prM. However, we observed that the more recent, epidemic-associated dengue 3 strains from Singapore and Malaysia of the late 1980s and early 1990s were more closely related to the Thai cluster, implying their evolution from the latter, and emphasizing the importance of viral spread via increasing travel within the Southeast Asian area and elsewhere. Nucleotide sequence analysis of the NS3 genes of dengue viruses can serve to advance the understanding of the epidemiology and evolution of these viruses.

Amino Acid Sequence↗
PubMed2006

Artificial receptors in serologic tests for the early diagnosis of dengue virus infection.

BACKGROUND: Because of the range and nonspecificity of clinical presentations of dengue virus infections, we felt there was a need to create diagnostic tests. We used artificial receptors for the virus to develop serologic assays to detect dengue virus infection. METHODS: We coated a quartz crystal microbalance (QCM) with molecularly imprinted polymers specific for nonstructural protein 1 of flavivirus. These artificial receptors were specifically created on a QCM chip by polymerization of monomers and were cross-linked in the presence of the epitope site of nonstructural protein 1. We tested serum samples from patients with confirmed cases of dengue reported to the Center for Disease Control in Taipei. Samples were diluted 100-fold; no other sample pretreatment was used. The QCM response was compared with results of monoclonal ELISA. RESULTS: QCM signals were >15 Hz in 18 of 21 (86%) of dengue samples and in 0 of 16 control samples. The correlation (r2) of the QCM response and the ELISA result was 0.73. Within-run and run-to-run imprecisions (CV) were 4%-28% and 10%-32%, respectively. CONCLUSIONS: The described assay offers a serologic technique for diagnosis of early viremia. The results illustrate the potential of well-organized polymers on the highly sensitive sensor system for diagnostic and biotechnological applications.

Antibodies, Monoclonal↗
PubMed2004

Dengue vaccine: priorities and progress.

Dengue transmission has increased considerably in the past 20 years. Currently, it can only be reduced by mosquito control; however, the application of vector-control methods are labor intensive, require discipline and diligence, and are hard to sustain. In this context, a safe dengue vaccine that confers long-lasting protection against infection with the four dengue viruses is urgently required. This review will discuss the requirements of a dengue vaccine, problems, and advances that have been made. Finally, new targets for research will be presented.

Animals↗
PubMedDate not supplied

Dengue 2 virus enhancement in asthmatic and non asthmatic individual.

During the 1981 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) Cuban epidemic, bronchial asthma (BA) was frequently found as a personal or family antecedent in dengue hemorrhagic fever patients. Considering that antibody dependent enhancement (ADE) plays an important role in the etiopathogenic mechanism of DHF/DSS, we decide to study the Dengue 2 virus (D2V) capability of replication in peripheral blood leukocytes (PBL) from asthmatic patients and healthy persons. In 90% of asthmatic patients and 53.8% of control group it was obtained PBL with a significant D2V enhancing activity (X2 p < 0.01). Power enhancement was higher in asthmatic group. This is the first in vitro study relating BA and the dengue 2 virus immuno enhancement. The results obtained support the role of BA as a risk factor for DHF/DSS as already described on epidemiological data.

Adolescent↗
PubMedDate not supplied

Dengue in Brazil--situation, transmission and control--a proposal for ecological control.

This article discusses dengue in terms of its conceptual and historical aspects, epidemiological and clinical/pathological nature, and evolution up to the present situation in Brazil. The author discusses the ecological relationship in both the production of dengue and its control. Comparison is made between traditional dengue-control programs and a proposed socially-controlled program of an ecological nature without the use of insecticides. Stress is placed on interdisciplinary technical and scientific activity, broadbased participation by communities in discussing methodological aspects involving them, and prospective evaluation comparing the communities selected for intervention and control communities with regard to clinical and subclinical dengue cases and vector infestation rates in relation to climatic, socio-economic, and behavioural factors.

Aedes↗
PubMedDate not supplied

A simple reverse transcription-polymerase chain reaction for dengue type 2 virus identification.

We show here a simplified reverse transcription-polymerase chain reaction (RT-PCR) for identification of dengue type 2 virus. Three dengue type 2 virus strains, isolated from Brazilian patients, and yellow fever vaccine 17DD, as a negative control, were used in this study. C6/36 cells were infected with the virus, and tissue culture fluids were collected after 7 days of infection period. The RT-PCR, a combination of RT and PCR done after a single addition of reagents in a single reaction vessel was carried out following a digestion of virus with 1% Nonidet P-40. The 50 microliters assay reaction mixture included 50 pmol of a dengue type 2 specific primer pair amplifying a 210 base pair sequence of the envelope protein gene, 0.1 mM of the four deoxynucleoside triphosphates, 7.5 U of reverse transcriptase, and IU of thermostable Taq DNA polymerase. The reagent mixture was incubated for 15 min at 37 degrees C for RT followed by a variable amount of cycles of two-step PCR amplification (92 degrees C for 60 sec, 53 degrees C for 60 sec) with slow temperature increment. The PCR products were subjected to 1.7% agarose gel electrophoresis and visualized with UV light after gel incubation in ethidium bromide solution. DNA bands were observed after 25 and 30 cycles of PCR. Virus amount as low as 10(2.8) TCID 50/ml was detected by RT-PCR. Specific DNA amplification was observed with the three dengue type 2 strains. This assay has advantages compared to other RT-PCRs: it avoids laborious extraction of virus RNA; the combination of RT and PCR reduces assay time, facilitates the performance and reduces risk of contamination; the two-step PCR cycle produces a clear DNA amplification, saves assay time and simplifies the technique.

Dengue↗
PubMed2005

Hemorrhagic encephalopathy in dengue shock syndrome: a case report.

Dengue fever is the most important arboviral infection in the world, with an estimated 100 million cases per year and 2.5 billion people at risk. Encephalopathy is a rare complication of dengue virus infection and may occur as a consequence of intracranial hemorrhage, cerebral edema, hyponatremia, cerebral anoxia, fulminant hepatic failure with portosystemic encephalopathy, microcapillary hemorrhage or release of toxic products. We report a rare case of hemorrhagic encephalopathy in dengue shock syndrome caused by type 3 dengue virus.

Adult↗
PubMed2000

Detection of dengue virus neutralizing antibodies in bats from Costa Rica and Ecuador.

Neutralizing antibodies for dengue virus serotypes 1 and 2 and serotypes 2 and 3 were detected in 1998 in 12 of 53 (22.6%) and 3 of 10 (30.0%) bats sampled in Costa Rica and Ecuador, respectively. Dengue is a consistent health problem in the two Costa Rican communities in which bats were sampled. The high percentage of bats with neutralizing antibodies to dengue virus in these two Costa Rican communities suggests that bats may become infected with dengue virus. This appears to be the case in Costa Rica and Ecuador.

Animals↗
PubMedDate not supplied

Dengue reemergence in Argentina.

Aedes aegypti, eradicated from Argentina in 1963, has now reinfested the country as far south as Buenos Aires. In 1997, four persons with travel histories to Brazil, Ecuador, or Venezuela had confirmed dengue, and surveillance for indigenous transmission allowed the detection of 19 dengue cases in Salta Province. These cases of dengue are the first in Argentina since 1916 and represent a new southern extension of dengue virus.

Aedes↗
PubMed2003

Laboratory surveillance of dengue in Argentina, 1995-2001.

Local transmission of dengue fever virus in Argentina is increased by the presence of Aedes aegypti mosquitoes and dengue outbreaks in neighboring countries. From 1995 to 2001, a laboratory-based active surveillance program detected 922 dengue cases. Indigenous transmission involving dengue-1 and -2 serotypes was confirmed only in subtropical areas in northern Argentina.

Adolescent↗