High levels of interferon alpha in the sera of children with dengue virus infection.
ABSTRACT We measured the levels of interferon alpha (IFN alpha) in the sera of Thai children hospitalized with dengue hemorrhagic fever (DHF) or dengue fever (DF) to examine the role of IFN alpha in dengue virus infections of humans. The percentage of patients who had detectable levels of IFN alpha (> or = 3 U/ml) was higher in patients with DHF (80%, P < 0.001) and in patients with DF (60%, P < 0.001) than in healthy Thai children (7%). The levels of IFN alpha were higher in patients with DHF and in patients with DF on the first few days after the onset of fever than in healthy Thai children. The average levels of IFN alpha in patients with DHF were high two days before defervescence, decreasing gradually until the day of defervescence. There was a subset of patients with DHF who had increasing levels of IFN alpha after defervescence. However, the levels of IFN alpha in patients with DF were not high after fever subsided. The levels of IFN alpha were not different among children with DHF grades 1, 2 and 3. Among patients with DHF, T lymphocytes were activated to a higher degree in high IFN alpha producers than in low IFN alpha producers. These results indicate that similarly high levels of IFN alpha are produced in vivo during the acute stages of DHF and DF, and that high levels of IFN alpha remain after fever subsides in some patients with DHF, but not in patients with DF.
- SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Viral RNA-host protein interactions are critical for replication of flaviviruses, a genus of positive-strand RNA viruses comprising major vector-borne human pathogens including dengue viruses (DENV). We examined three conserved host RNA-binding proteins (RBPs) G3BP1, G3BP2 and CAPRIN1 in dengue virus (DENV-2) infection and found them to be novel regulators of the interferon (IFN) response against DENV-2. The three RBPs were required for the accumulation of the protein products of several interferon stimulated genes (ISGs), and for efficient translation of PKR and IFITM2 mRNAs. This identifies G3BP1, G3BP2 and CAPRIN1 as novel regulators of the antiviral state. Their antiviral activity was antagonized by the abundant DENV-2 non-coding subgenomic flaviviral RNA (sfRNA), which bound to G3BP1, G3BP2 and CAPRIN1, inhibited their activity and lead to profound inhibition of ISG mRNA translation. This work describes a new and unexpected level of regulation for interferon stimulated gene expression and presents the first mechanism of action for an sfRNA as a molecular sponge of anti-viral effectors in human cells.PLoS Pathogens 07/2014; 10(7):e1004242. · 8.14 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Dengue fever is the most important arthropod-borne viral disease worldwide, affecting 50-100 million individuals annually. The clinical picture associated with acute dengue virus (DENV) infections ranges from classical febrile illness to life-threatening disease. The innate immunity is the first line of defense in the control of viral replication. This review will examine the particular role of natural killer (NK) cells in DENV infection. Over recent years, our understanding of the interplay between NK cells and viral pathogenesis has improved significantly. NK cells express an array of inhibitory and activating receptors that enable them to detect infected targets while sparing normal cells, and to recruit adaptive immune cells. To date, the exact mechanism by which NK cells may contribute to the control of DENV infection remains elusive. Importantly, DENV has acquired mechanisms to evade NK cell responses, further underlining the relevance of these cells in pathophysiology. Hence, understanding how NK cells affect the outcome of DENV infection could benefit the management of this acute disease.Frontiers in Immunology 01/2014; 5:209.
- [Show abstract] [Hide abstract]
ABSTRACT: Uncontrolled and intricate production of inflammatory factors is the characteristic feature of dengue infection. The triggering receptor expressed in myeloid cells-1 (TREM-1), expressed on the surface of monocytes and neutrophils, is capable of enhancing and regulating the inflammatory response via the production of different mediators in bacterial and viral infections. Here, both the expression of TREM-1 on human monocytes and neutrophils from peripheral blood of dengue infected individuals, as well as the levels of the soluble form of TREM-1 (sTREM-1) in the sera of these patients were compared against healthy controls. A significant reduction of TREM-1 expression was observed in neutrophils during the first days of infection, followed by a gradual recovery throughout the course of infection. Also, sera from DENV-infected patients exhibited significantly higher sTREM-1 levels than healthy individuals. The difference was more pronounced during the first 5 days after the onset of symptoms. These findings highlight the dynamic process of TREM-1 expression during DENV infection. We hypothesized that increment of free sTREM-1 could be a compensatory mechanism aiming to counteract the inflammatory process elicited during DENV infection.Immunology letters 01/2014; · 2.91 Impact Factor