Dengue virus 3 genotype 1 associated with dengue fever and dengue hemorrhagic fever, Brazil.
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ABSTRACT:
SUBMITTER: Barcelos Figueiredo L
PROVIDER: S-EPMC2600180 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Dengue infection is the most prevalent arthropod-borne viral disease in subtropical and tropical regions, whose primary vector is Aedes aegypti mosquitoes. The mechanisms of dengue virus (DENV) pathogenesis are little understood because we have no good disease models. Only humans develop symptoms (dengue fever, DF, or dengue hemorrhagic fever, DHF) and research has been limited to studies involving patients. Samples from serum, brain, cerebellum, heart, lungs, liver, and kidneys from a 13-year-old male patient that died with hemorrhagic manifestations were sent for differential diagnosis at Adolfo Lutz, using both classical virological methods (RT-qPCR, virus isolation, ELISA, and hemagglutination inhibition test) and immunohistochemistry (IHQ). A DENV serotype 4 was detected by a DENV multiplex RT-qPCR, and the C6/36 cell supernatant was used for NGS using Minion. Lesions were described in the heart, liver, lung, and kidney with positive IHQ in endothelial cells of the brain, cerebellum, heart, and kidney, and also in hepatocytes and Kuppfer cells. A whole genome was obtained, revealing a DENV-4 genotype II, with no evidence of secondary dengue infection.
| S-EPMC9433511 | biostudies-literature
Project description: Not available
| S-EPMC2609867 | biostudies-literature
Project description:To identify genes associated with the clinical presentation of dengue, 50 cases of probable or possible dengue hemorrhagic fever (DHF), 236 dengue fever (DF), and 236 asymptomatic infections were genotyped for 593 single-nucleotide polymorphisms (SNPs) in 56 genes across the type 1 interferon (IFN) response pathway as well as other important candidate genes. By single locus analysis comparing DHF with DF, 11 of the 51 markers with P<0.05 were in the JAK1 gene. Five markers were significantly associated by false discovery rate criteria (q<0.20 when P<6 × 10(-4)). The JAK1 SNPs showed differential distribution by ethnicity and ancestry consistent with epidemiologic observations in the Americas. The association remained significant after controlling for ancestry and income. No association was observed with markers in the gene encoding CD209 (DC-SIGN). An association between DHF and JAK1 polymorphisms is in agreement with expression profiles showing generalized decreased type 1 IFN-stimulated gene expression in these patients.
| S-EPMC2950898 | biostudies-literature
Project description:BACKGROUND: Dengue virus (DENV) infection is the most common arthropod-borne viral disease in man and there are approximately 100 million infections annually. Despite the global burden of DENV infections many important questions regarding DENV pathogenesis remain unaddressed due to the lack of appropriate animal models of infection and disease. A major problem is the fact that no non-human species naturally develop disease similar to human dengue fever (DF) or dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Apart from other risk factors for severe dengue such as host genetics and secondary infection with a heterologous DENV, virus virulence is a risk factor that is not well characterized. RESULTS: Three clinical DENV-1 isolates from Cambodian patients experiencing the various forms of dengue disease (DF, DHF, and DSS) were inoculated in BALB/c mice at three different concentrations. The DENV-1 isolates had different organ and cell tropism and replication kinetics. The DENV-1 isolate from a DSS patient infected the largest number of mice and was primarily neurotropic. In contrast, the DENV-1 isolates from milder clinical dengue cases infected predominantly lungs and liver, and to a lesser extent brain. In addition, infection with the DENV isolate derived from a DSS patient persisted for more than two weeks in a majority of mice compared to the other DENV-1 isolates that peaked during the first week. CONCLUSIONS: These results confirm the in vitro findings of the same DENV-1 isolates, that showed that the isolate derived from a DSS patient can be distinguished based on phenotypic characteristics that differ from the isolates derived from a DF and DHF case 1. We observed in this study that the DSS virus isolate persist longer in vivo with extensive neuroinvasion in contrast to the other DENV-1 isolates originating in milder human cases. Genomic characterization of the three clinical isolates identified six amino acid substitutions unique for the DSS isolates that were located both in structural genes (M and E) and in non-structural genes (NS1, NS3, and NS5). The characterization of these clinically distinct DENV-1 isolates highlight that DENVs within the same genotype may have different in vivo phenotypes. HIGHLIGHTS: • Clinical DENV-1 isolates have different organ tropism in BALB/c mice.• The isolate from a DSS patient is primarily neurotropic compared to the other isolates.• The DENV-1 isolates have different in vivo replication kinetics.• The isolate from a DSS patient persists longer compared to the other isolates.• These phenotypic differences confirm our earlier in vitro findings with the same DENV-1 isolates. Thus, DENVs within the same serotype and genotype may differ enough to affect clinical conditions in vivo.
| S-EPMC3170302 | biostudies-literature
Project description:High levels of viremia and chemokines and cytokines underlie the progression of severe dengue disease. Dengue virus (DENV) preferentially infects peripheral blood monocytes, which secrete elevated levels of immunomediators in patients with severe disease. Further, DENV nonstructural proteins (NS) are capable of modifying intracellular signaling, including interferon inhibition. We demonstrate that peak secretions of immunomediators such as IL-6, IL-8, IP-10, TNF? or IFN? in DENV-infected monocytes correlate with maximum virus production and NS4B and NS5 are primarily responsible for the induction of immunomediators. Furthermore, we demonstrate that sequential NS4AB processing initiated by the viral protease NS2B3(pro) and via the intermediate 2KNS4B significantly enhances immunomediator induction. While the 2K-signal peptide is not essential for immunomediator induction, it plays a synergistic role with NS4B. These data suggest that NS4B maturation is important during innate immune signaling in DENV-infected monocytes. Given similar NS4B topologies and polyprotein processing across flaviviruses, NS4B may be an attractive target for developing Flavivirus-wide therapeutic interventions.
| S-EPMC3184475 | biostudies-literature
Project description:BackgroundGenetic risk factors for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and dengue fever (DF) are limited, in particular there are sparse data on genetic risk across diverse populations.MethodsWe conducted a genome-wide association study (GWAS) in a derivation and validation sample of 7, 460 participants of Latin American, South Asian, and South East Asian ancestries. We then developed a weighted polygenic risk score (PRS) for each participant in each of the validation cohorts of the three ancestries to predict the risk of DHF/DSS compared to DF, DHF/DSS compared to controls, and, DF compared to controls.FindingsThe risk of DHF/DSS was significantly increased, odds ratio [OR] 1.84 (95%CI 1.47 to 2.31) (195 SNPs), compared to DF, fourth PRS quartile versus first quartile, in the validation cohort. The risk of DHF/DSS compared to controls was increased (OR=3.94; 95% CI 2.84 to 5.45) (278 SNPs), as was the risk of DF compared to controls (OR=1.97; 95%CI 1.63 to 2.39) (251 SNPs). Risk increased in a dose-dependent manner with increase in quartiles of PRS across comparisons. Significant associations persisted for PRS built within ancestries and applied to the same or different ancestries as well as for PRS built for one outcome (DHF/DSS or DF) and applied to the other.InterpretationThere is a strong genetic effect that predisposes to risk of DHF/DSS and DF. The genetic risk for DHF/DSS is higher than that for DF when compared to controls, and this effect persists across multiple ancestries.
| S-EPMC6940652 | biostudies-literature
Project description:New World arenaviruses can cause chronic infection in rodents and hemorrhagic fever in humans. We identified a Sabiá virus-like mammarenavirus in a patient with fatal hemorrhagic fever from São Paulo, Brazil. The virus was detected through virome enrichment and metagenomic next-generation sequencing technology.
| S-EPMC7258484 | biostudies-literature
Project description:Dengue viruses circulate in both human and sylvatic cycles. Although dengue viruses (DENV) infecting humans can cause major epidemics and severe disease, relatively little is known about the epidemiology and etiology of sylvatic dengue viruses. A 20-year-old male developed dengue hemorrhagic fever (DHF) with thrombocytopenia (12,000/ul) and a raised hematocrit (29.5% above baseline) in January 2008 in Malaysia. Dengue virus serotype 2 was isolated from his blood on day 4 of fever. A phylogenetic analysis of the complete genome sequence revealed that this virus was a member of a sylvatic lineage of DENV-2 and most closely related to a virus isolated from a sentinel monkey in Malaysia in 1970. This is the first identification of a sylvatic DENV circulating in Asia since 1975.
| S-EPMC2669127 | biostudies-literature
Project description:BACKGROUND:The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease. METHODS:A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period of six years (2008 - 2013) was performed. Patient's demographics, clinical and laboratory findings were recorded via structured data collection form. Patients were categorized into dengue fever (DF) and dengue hemorrhagic fever (DHF). Appropriate statistical methods were used to compare these two groups in order to determine difference in clinico-laboratory characteristics and to identify independent risk factors of DHF. RESULTS:A total 667 dengue patients (30.69?±?16.13 years; Male: 56.7 %) were reviewed. Typical manifestations of dengue like fever, myalgia, arthralgia, headache, vomiting, abdominal pain and skin rash were observed in more than 40 % patients. DHF was observed in 79 (11.8 %) cases. Skin rash, dehydration, shortness of breath, pleural effusion and thick gall bladder were more significantly (P?<?0.05) associated with DHF than DF. Multivariate regression analysis demonstrated presence of age?>?40 years (OR: 4.1, P?<?0.001), secondary infection (OR: 2.7, P?=?0.042), diabetes mellitus (OR: 2.8, P?=?0.041), lethargy (OR: 3.1, P?=?0.005), thick gallbladder (OR: 1.7, P?=?0.029) and delayed hospitalization (OR: 2.3, P?=?0.037) as independent predictors of DHF. Overall mortality was 1.2 % in our study. CONCLUSIONS:Current study demonstrated that DF and DHF present significantly different clinico-laboratory profile. Older age, secondary infection, diabetes mellitus, lethargy, thick gallbladder and delayed hospitalization significantly predict DHF. Prior knowledge of expected clinical profile and predictors of DHF/DSS development would provide information to identify individuals at higher risk and on the other hand, give sufficient time to clinicians for reducing dengue related morbidity and mortality.
| S-EPMC4590689 | biostudies-other
Project description:Purpose: Dengue virus (DENV) causes dengue hemorrhagic fever (DHF) and have been often associated to fatal cases worldwide. The liver is one of the most important target tissues in severe cases, due to its intense viral replication and role in metabolism. microRNAs (miRNA) role during infection is crucial to understand the regulatory mechanisms of DENV infection, and can help in diagnostic and anti-viral therapies development. Methods: miRNoma sequencing of ten fatal cases and compared to controls, to characterize the miRNAs expression profile of the human formalin fixed paraffin embedded (FFPE) liver tissue during DHF Results: Eight miRNAs were differentially expressed in hepatic FFPE tissue: miR-126-5p (log2FC 3.09; p< 0,001), a regulatory molecule of endothelial cells, and miR-133a-3p (100-fold, p<0,001) were up regulated in DHF and miR-122-5p (a liver-specific miRNA), miR-146a-5p (Interferon-regulator), miR-10b-5p, miR-204-5p, miR-148a-5p and miR-423-5p were down regulated. Enrichment analysis of KEGG pathways and GO terms with predicted target genes of overexpressed miRNAs revealed regulatory pathways of apoptosis, involving MAPK, RAS, CDK and FAS and immune response pathways were related to NF- kB, CC and CX families, IL and TLR. The enrichment analysis using target genes of down regulated miRNAs in DHF also identified in most pathways of apoptosis and biosynthetic pathways. Conclusions: This is the first description of the human miRNA profile in liver tissues from DHF cases. The results demonstrated the association of miR-126-5p, miR-122-5p and miR-146a-5p with DHF liver pathogenesis, involving endothelial repair and vascular permeability regulation, control of homeostasis and expression of inflammatory cytokines.
2018-07-31 | GSE84536 | GEO