Guanylate-binding protein 1 participates in cellular antiviral response to dengue virus

BACKGROUND: Dengue virus (DENV), the causative agent of human Dengue hemorrhagic fever, is a mosquito-borne virus found in tropical and sub-tropical regions around the world. Vaccines against DENV are currently unavailable. Guanylate-binding protein 1 (GBP1) is one of the Interferon (IFN) stimulated genes (ISGs) and has been shown important for host immune defense against various pathogens. However, the role of GBP1 during DENV infection remains unclarified. In this study, we evaluated the relevance of GBP1 to DENV infection in in vitro model. FINDINGS: Quantitative RT-PCR (qRT-PCR) and Western blot showed that the expression of mouse Gbp1 was dramatically upregulated in DENV-infected RAW264.7 cells. The intracellular DENV loads were significantly higher in Gbp1 silenced cells compared with controls. The expression levels of selective anti-viral cytokines were decreased in Gbp1 siRNA treated cells, while the transcription factor activity of NF-κB was impaired upon GBP1 silencing during infection. CONCLUSIONS: Our data suggested that GBP1 plays an antiviral role during DENV infection

The spectrum of low-pTp_{T} J/ψJ/\psi in heavy ion collisions in a fractal description

Transverse momentum spectrum of particles in hadron gas are affected by flow, quantum and strong interaction effects. Previously, most models focus on only one of the three effects but ignore others. The unconsidered effects are taken into the fitted parameters. In this paper, we study the three effects together from a new fractal angle by physical calculation instead of data fitting. Near the critical temperature, the three effects induce $J/\psi$ and neighboring meson to form a two-meson structure. We set up a two-particle fractal (TPF) model to describe this structure. We propose that under the three effects, $J/\psi$-$\pi$ two-meson state, $J/\psi$ and $\pi$ two-quark states form a self-similarity structure. With evolution, the two-meson structure disintegrate. We introduce an influencing factor $q_{fqs}$ to describe the flow, quantum and strong interaction effects and an escort factor $q_2$ to describe the binding force and the three effects. By solving the probability and entropy equations, we obtain the values of $q_{fqs}$ and $q_2$ at different collision energies and centrality classes. By substituting the value of $q_{fqs}$ into distribution function, we obtain the transverse momentum spectrum of low-$p_T$ $J/\psi$ and find it in good agreement with experimental data. We also analyze the evolution of $q_{fqs}$ with the temperature. It is found that $q_{fqs}$ is larger than 1. This is because the three effects decrease the number of microstates. We also find $q_{fqs}$ decreases with decreasing the temperature. This is consistent with the fact that with the system expansion, the influence of the three effects decrease.Comment: 9 pages, 3 figure

Glycosphingolipid GM3 is Indispensable for Dengue Virus Genome Replication

Dengue virus (DENV) causes the most prevalent arthropod-borne viral disease of humans worldwide. Glycosphingolipids (GSLs) are involved in virus infection by regulating various steps of viral-host interaction. However, the distinct role of GSLs during DENV infection remains unclear. In this study, we used mouse melanoma B16 cells and their GSL-deficient mutant counterpart GM95 cells to study the influence of GSLs on DENV infection. Surprisingly, GM95 cells were highly resistant to DENV infection compared with B16 cells. Pretreatment of B16 cells with synthetase inhibitor of GM3, the most abundant GSLs in B16 cells, or silencing GM3 synthetase T3GAL5, significantly inhibited DENV infection. DENV attachment and endocytosis were not impaired in GM95 cells, but DENV genome replication was obviously inhibited in GM95 cells compared to B16 cells. Furthermore, GM3 was colocalized with DENV viral replication complex on endoplasmic reticulum (ER) inside the B16 cells. Finally, GM3 synthetase inhibitor significantly reduced the mortality rate of suckling mice that challenged with DENV by impairing the viral replication in mouse brain. Taken together, these data indicated that GM3 was not required for DENV attachment and endocytosis, however, essential for viral genome replication. Targeting GM3 could be a novel strategy to inhibit DENV infection

Upregulation of Glutamic-Oxaloacetic Transaminase 1 Predicts Poor Prognosis in Acute Myeloid Leukemia

One of the key features of acute myeloid leukemia (AML), a group of very aggressive myeloid malignancies, is their strikingly heterogenous outcomes. Accurate biomarkers are needed to improve prognostic assessment. Glutamate oxaloacetate transaminase 1 (GOT1) is essential for cell proliferation and apoptosis by regulating cell's metabolic dependency on glucose. It is unclear whether the expression level of GOT1 has clinical implications in AML. Therefore, we analyzed the data of 155 AML patients with GOT1 expression information from The Cancer Genome Atlas (TCGA) database. Among them, 84 patients were treated with chemotherapy alone, while 71 received allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both treatment groups, high GOT1 expression was associated with shorter event-free survival (EFS) and overall survival (OS) (all P = 60 years, white blood cell count >= 15 x 10(9)/L, bone marrow blasts >= 70%, and DNMT3A, RUNX1 or TP53 mutations (all P <0.05); but in the allo-HSCT group, the only independent risk factor for survival was high GOT1 expression (P <0.05 for both EFS and OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the genes related to GOT1 expression were mainly concentrated in "hematopoietic cell lineage" and "leukocyte transendothelial migration" signaling pathways. Collectively, GOT1 expression may be a useful prognostic indicator in AML, especially in patients who have undergone allo-HSCT