Dengue is one of the main public health concerns worldwide. Recent estimates indicate that over 390 million people are infected annually with the dengue virus (DENV), resulting in thousands of deaths. Among the DENV nonstructural proteins, the NS1 protein is the only one whose function during replication is still unknown. NS1 is a 46-to 55-kDa glycoprotein commonly found as both a membrane-associated homodimer and a soluble hexameric barrel-shaped lipoprotein. Despite its role in the pathogenic process, NS1 is essential for proper RNA accumulation and virus production. In the present study, we identified that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with intracellular NS1. Molecular docking revealed that this interaction occurs through the hydrophobic protrusion of NS1 and the hydrophobic residues located at the opposite side of the catalytic site. Moreover, addition of purified recombinant NS1 enhanced the glycolytic activity of GAPDH in vitro. Interestingly, we observed that DENV infection promoted the relocalization of GAPDH to the perinuclear region, where NS1 is commonly found. Both DENV infection and expression of NS1 itself resulted in increased GAPDH activity. Our findings indicate that the NS1 protein acts to increase glycolytic flux and, consequently, energy production, which is consistent with the recent finding that DENV induces and requires glycolysis for proper replication. This is the first report to propose that NS1 is an important modulator of cellular energy metabolism. The data presented here provide new insights that may be useful for further drug design and the development of alternative antiviral therapies against DENV. IMPORTANCE Dengue represents a serious public health problem worldwide and is caused by infection with dengue virus (DENV).Estimates indicate that half of the global population is at risk of infection, with almost 400 million cases occurring per year. The NS1 glycoprotein is found in both the intracellular and the extracellular milieus. Despite the fact that NS1 has been commonly associated with DENV pathogenesis, it plays a pivotal but unknown role in the replication process. In an effort to understand the role of intracellular NS1, we demonstrate that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with NS1. Our results indicate that NS1 increases the glycolytic activity of GAPDH in vitro. Interestingly, the GAPDH activity was increased during DENV infection, and NS1 expression alone was sufficient to enhance intracellular GAPDH activity in BHK-21 cells. Overall, our findings suggest that NS1 is an important modulator of cellular energy metabolism by increasing glycolytic flux. Dengue is one of the major health problems in tropical regions. It is estimated that over 390 million people are infected annually with one of the four dengue virus (DENV) serotypes (1). The absence of both an effective tetravalent vaccine and therapeutic agents worsens the impact of the dengue burden. DENV, the most threatening member of the Flaviviridae family,...
The Brazilian NAT HIV, HCV, and HBV kit is an automated NAT system suitable for routine blood donor screening in a completely traceable process. The analytical sensitivity as well as the diagnostic sensitivity fulfilled all requirements set by the health ministry for blood donor screening. A significant number of transmission cases were prevented by the implementation of this important program.
Background Malaria can be transmitted by blood transfusion through donations collected from asymptomatic donors. Transfusion-transmitted malaria (TTM) poses a great risk to blood services worldwide. A good screening tool for Plasmodium spp. detection in blood banks must have a high sensitivity for prevention of TTM. However, in Brazilian blood banks, screening for malaria still relies on microscopy. Methods In Brazil, screening for human immunodeficiency virus type 1 (HIV), RNA/DNA for hepatitis C (HCV) and hepatitis B (HBV) viruses is mandatory for every blood donation and uses nucleic acid amplification testing (NAT). The aim of this study was to evaluate the inclusion of an assay for malaria to identify Plasmodium sp. from total nucleic acid (TNA; DNA/RNA) by targeting the 18S rRNA gene of the parasite. Results Considering the limitations of microscopy and the wide availability of the Brazilian NAT platform in the screening of blood units for HIV, HCV, and HBV, a molecular diagnostic tool was validated for detection of Plasmodium sp. in blood banks; a pilot study showed that using this novel NAT assay could reduce the risk of TTM. Conclusion The prototype HIV/HCV/HBV/malaria NAT assay was effective in detecting infected candidate donors and has good prospects to be applied in routine screening for preventing TTM.
The potential for transfusion transmission of dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) has raised concerns about the safety of the blood supply in endemic areas. In this study, nucleic acid testing (NAT) for ZIKV, DENV, and CHIKV RNA was performed in asymptomatic blood donor samples in the city of Campinas, located in the southeast region of Brazil (1962Brazil ( in 2015Brazil ( and 1775Brazil ( in 2016. The prevalence of reactive NAT was 0.15% in 2015 and 0.62% in 2016 for dengue, 0.05% in 2015 and 0.17% in 2016 for Zika, and 0% in both years for chikungunya. These results demonstrate the weakness of the clinical interview in screening these blood donors. Furthermore, positivity for ZIKV was detected in March 2015, 1 year before the first reported cases in the region. These data attest the feasibility of using donor samples held in library as a tool for retrospective epidemiological evaluation, which is particularly interesting considering emerging pathogens, for which data on their spread and penetrance are initially scarce.
We study the soldering formalism in the context of abelian p-form theories. We develop further the fusion process of massless antisymmetric tensors of different ranks into a massive p-form and establish its duality properties. To illustrate the formalism we consider two situations. First the soldering mass generation mechanism is compared with the Higgs and Julia-Toulouse mechanisms for mass generation due to condensation of electric and magnetic topological defects. We show that the soldering mechanism interpolates between them for even dimensional spacetimes, in this way confirming the Higgs/Julia-Toulouse duality proposed by Quevedo and Trugenberger \cite{QT} a few years ago. Next, soldering is applied to the study of duality group classification of the massive forms. We show a dichotomy controlled by the parity of the operator defining the symplectic structure of the theory and find their explicit actions.Comment: Reference [8] has been properly place
Hepatitis C virus (HCV) infection is a worldwide health problem. Nowadays, direct-acting antiviral agents (DAAs) are the main treatment for HCV; however, the high level of virus variability leads to the development of resistance-associated variants (RAVs). Thus, assessing RAVs in infected patients is important for monitoring treatment efficacy. The aim of our study was to investigate the presence of naturally occurring resistance mutations in HCV NS3 and NS5 regions in treatment-naïve patients. Ninety-six anti-HCV positive serum samples from blood donors at the Center of Hematology and Hemotherapy of Santa Catarina State (HEMOSC) were collected retrospectively in 2013 and evaluated in this study. HCV 1a (37.9%), 1b (25.3%), and 3a (36.8%) subtypes were found. The frequency of patients with RAVs in our study was 6.9%. The HCV NS5b sequencing reveled 1 sample with L320F mutation and 4 samples with the C316N/R polymorphism. The analysis of the NS3 region revealed the D168A/G/T (3.45%), S122G (1.15%), and V55A (2.3%) mutations. All samples from genotype 3a (36.8%) presented the V170 I/V non-synonymous mutation. In conclusion, we have shown that mutations in NS3 and NS5b genes are present in Brazilian isolates from therapy-naïve HCV patients.
A ingestão crônica de álcool pode provocar alterações estruturais em vários tecidos, inclusive no tecido ósseo. O objetivo desse estudo foi avaliar o efeito da ingestão de álcool etílico sobre a morfometria de fêmures e tíbias em ratas. Foram utilizados quarenta animais (4 meses de idade) divididos em cinco grupos (n=8) conforme a dieta líquida administrada: água (Gc-controle), solução alcoólica a 10% (GA1), solução de sacarose a 13,5% (GI1), solução alcoólica a 20% (GA2), solução de sacarose a 27% (GI2). Os grupos GI1 e GI2 receberam dietas controladas com mesmo valor calórico dos grupos GA1 e GA2, respectivamente. Após oito semanas, os animais foram sacrificados e os fêmures e tíbias removidos. O peso úmido dos espécimes foi avaliado em balança analítica. O comprimento e diâmetros (ântero-posterior e médio-lateral) foram medidos com paquímetro digital. Após, foram realizadas radiografias na metade distal dos espécimes para determinar a localização do tecido ósseo trabecular. Nesta região, secções transversais (1 mm) foram obtidas, em local padronizado, a fim de avaliar o percentual médio da área óssea cortical e medular. A análise estatística (ANOVA) não revelou diferenças significativas (P>0,05) para comprimento, diâmetro médio-lateral, diâmetro ântero-posterior e valores percentuais de área óssea cortical e área óssea medular. Pode-se concluir que o consumo de álcool etílico a 10% (que correspondeu a 24,36% das calorias diárias da dieta) e 20% (que correspondeu a 40,10% das calorias diárias da dieta) durante oito semanas em ratas adultas jovens não promoveu alterações morfológicas nos ossos longos.
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