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.
"This type I, IFN, is a crucial mediator of the antiviral response directly inhibiting viral replication and modulating downstream immune responses to counteract viral spread (18). Elevated IFN-α plasmatic levels are observed shortly after onset of symptoms in children and adult DENV-infected patients (19, 20). Recently, Gandini et al. (21) have shown that DENV2 efficiently activated IFN-α production by plasmacytoid dendritic cells (pDCs), which produced up to 1000-fold more IFN-α than other cell types in response to virus exposure. "
[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 05/2014; 5:209. DOI:10.3389/fimmu.2014.00209
"Infection with any of the DENV serotypes (DENV-1, -2, -3, and -4) is generally asymptomatic, but many cases develop dengue fever (DF) or result in severe forms of the disease, known as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS)  . Cases of dengue are characterized by an uncontrolled inflammatory response  , with massive production of soluble factors such as TNF-<alpha>, IFN-<alpha>, IL-6, IL-8, IL-10 and HMGB1, which are related to disease severity      . Monocytes are considered as the main target of DENV  and recently, Wong et al. demonstrated that different subpopulations of these cells (CD16 + and CD16 − ) are permissive to infection and capable of support the production of new infective virus particles. "
[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.
"To understand these mechanism studies are being focused on the role of T-cell immune response. After 1–2 days of onset fever during secondary infection, high concentrations of interferon alpha were recorded . High concentrations of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon γ were also studied during the onset of vascular permeability . "
[Show abstract][Hide abstract] ABSTRACT: Dengue virus infection is a serious health problem infecting 2.5 billion people worldwide. Dengue is now endemic in more than 100 countries, including Pakistan. Each year hundreds of people get infected with dengue in Pakistan. Currently, there is no vaccine available for the prevention of Dengue virus infection due to four viral serotypes. Dengue infection can cause death of patients in its most severity, meanwhile many antiviral compounds are being tested against dengue virus infection to eradicate this disease but still there is a need to develop an efficient, low-cost and safe vaccine that can target all the four serotypes of dengue virus. This review summarizes dengue molecular virology, important drug targets, prevalence in Pakistan, diagnosis, treatment and medicinal plant inhibitors against dengue.
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