How Ebola and Marburg viruses battle the immune system

Johns Hopkins University, Baltimore, Maryland, United States
Nature reviews. Immunology (Impact Factor: 34.99). 08/2007; 7(7):556-67. DOI: 10.1038/nri2098
Source: PubMed


The filoviruses Ebola and Marburg have emerged in the past decade from relative obscurity to serve now as archetypes for some of the more intriguing and daunting challenges posed by such agents. Public imagination is captured by deadly outbreaks of these viruses and reinforced by the specter of bioterrorism. As research on these agents has accelerated, it has been found increasingly that filoviruses use a combination of familiar and apparently new ways to baffle and battle the immune system. Filoviruses have provided thereby a new lens through which to examine the immune system itself.

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    • "However in the case of a systemic infection such as EBOV, both the viral production and the treatment effectiveness may differ in each compartment of the infection. Second the infected mice lacked a type-I IFN response, which is a critical component of the immune response against systemic viral infections (Mohamadzadeh et al., 2007). Despite the alteration of the innate immune response, the viremia dropped after the peak, which was interpreted in the model as an effect of target cell exhaustion and rapid elimination of infected cells. "
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    ABSTRACT: The polymerase inhibitor favipiravir is a candidate for the treatment of Ebola virus disease. Here, we designed a mathematical model to characterize the viral dynamics in 20 mice experimentally infected with Ebola virus, which were either left untreated or treated with favipiravir at 6 or 8 days post infection. This approach provided estimates of kinetic parameters of Ebola virus reproduction, such as the half-life of productively infected cells, of about 6 hours, and the basic reproductive number which indicates that virus produced by a single infected cell productively infects about 9 new cells. Furthermore, the model predicted that favipiravir efficiently blocks viral production, reaching an antiviral effectiveness of 95% and 99.6% at 2 and 6 days after initiation of treatment, respectively. The model could be particularly helpful to guide future studies evaluating favipiravir in larger animals. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Sep 2015 · Antiviral research
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    • "Controlled inflammatory responses are necessary to promote protective immunity and overcome pathogen challenge after infection. However, certain pathogens have evolved to evade immune recognition and clearance through NF-κB and MAPK signaling inhibition [54]. Accordingly, one day post-infection we found a robust increase in the transcription of genes involved in innate immune recognition (Data Not Shown); however, expression of these genes rapidly decreased to basal levels, and in certain cases, was even lower than those of the controls, suggesting suppression of critical sensing molecules to mobilize protective immunity against pathogens. "
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    ABSTRACT: Gastrointestinal (GI) anthrax results from the ingestion of Bacillus anthracis. Herein, we investigated the pathogenesis of GI anthrax in animals orally infected with toxigenic non-encapsulated B. anthracis Sterne strain (pXO1+ pXO2-) spores that resulted in rapid animal death. B. anthracis Sterne induced significant breakdown of intestinal barrier function and led to gut dysbiosis, resulting in systemic dissemination of not only B. anthracis, but also of commensals. Disease progression significantly correlated with the deterioration of innate and T cell functions. Our studies provide critical immunologic and physiologic insights into the pathogenesis of GI anthrax infection, whereupon cleavage of mitogen-activated protein kinases (MAPKs) in immune cells may play a central role in promoting dysfunctional immune responses against this deadly pathogen.
    Full-text · Article · Jun 2014 · PLoS ONE
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    • "There are several promising vaccine candidates that have demonstrated immunogenicity and efficacy in animal models of disease. These platforms include the Venezuelan equine encephalitis (VEE) virus-like replicon (VRP), adenovirus 5 (Ad5), vesicular stomatitis virus-(VSV-) based vaccines, and virus-like particles (VLPs) [17, 18]. In early studies, classical approaches were attempted for filovirus vaccines attenuated or inactivated viral preparations; however, protection in primate animal models showed variable and moderate success coupled with the risk of revertants or incomplete inactivation result in these approaches being unacceptable for future use in humans [19–27]. "
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    ABSTRACT: Infection with many emerging viruses, such as the hemorrhagic fever disease caused by the filoviruses, Marburg (MARV), and Ebola virus (EBOV), leaves the host with a short timeframe in which to mouse a protective immune response. In lethal cases, uncontrolled viral replication and virus-induced immune dysregulation are too severe to overcome, and mortality is generally associated with a lack of notable immune responses. Vaccination studies in animals have demonstrated an association of IgG and neutralizing antibody responses against the protective glycoprotein antigen with survival from lethal challenge. More recently, studies in animal models of filovirus hemorrhagic fever have established that induction of a strong filovirus-specific cytotoxic T lymphocyte (CTL) response can facilitate complete viral clearance. In this review, we describe assays used to discover CTL responses after vaccination or live filovirus infection in both animal models and human clinical trials. Unfortunately, little data regarding CTL responses have been collected from infected human survivors, primarily due to the low frequency of disease and the inability to perform these studies in the field. Advancements in assays and technologies may allow these studies to occur during future outbreaks.
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