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      Enterovirus infections of the central nervous system

      review-article
      , , , *
      Virology
      Elsevier Inc.
      Enteroviruses, CNS

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          Abstract

          Enteroviruses (EV) frequently infect the central nervous system (CNS) and induce neurological diseases. Although the CNS is composed of many different cell types, the spectrum of tropism for each EV is considerable. These viruses have the ability to completely shut down host translational machinery and are considered highly cytolytic, thereby causing cytopathic effects. Hence, CNS dysfunction following EV infection of neuronal or glial cells might be expected. Perhaps unexpectedly given their cytolytic nature, EVs may establish a persistent infection within the CNS, and the lasting effects on the host might be significant with unanticipated consequences. This review will describe the clinical aspects of EV-mediated disease, mechanisms of disease, determinants of tropism, immune activation within the CNS, and potential treatment regimes.

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          Most cited references192

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          Clinical features, diagnosis, and management of enterovirus 71.

          Although poliomyelitis has been mostly eradicated worldwide, large outbreaks of the related enterovirus 71 have been seen in Asia-Pacific countries in the past 10 years. This virus mostly affects children, manifesting as hand, foot, and mouth disease, aseptic meningitis, poliomyelitis-like acute flaccid paralysis, brainstem encephalitis, and other severe systemic disorders, including especially pulmonary oedema and cardiorespiratory collapse. Clinical predictors of severe disease include high temperature and lethargy, and lumbar puncture might reveal pleocytosis. Many diagnostic tests are available, but PCR of throat swabs and vesicle fluid, if available, is among the most efficient. Features of inflammation, particularly in the anterior horns of the spinal cord, the dorsal pons, and the medulla can be clearly seen on MRI. No established antiviral treatment is available. Intravenous immunoglobulin seems to be beneficial in severe disease, perhaps through non-specific anti-inflammatory mechanisms, but has not been tested in any formal trials. Milrinone might be helpful in patients with cardiac dysfunction. Copyright © 2010 Elsevier Ltd. All rights reserved.
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            Interferon modulation of cellular microRNAs as an antiviral mechanism.

            RNA interference through non-coding microRNAs (miRNAs) represents a vital component of the innate antiviral immune response in plants and invertebrate animals; however, a role for cellular miRNAs in the defence against viral infection in mammalian organisms has thus far remained elusive. Here we show that interferon beta (IFNbeta) rapidly modulates the expression of numerous cellular miRNAs, and that eight of these IFNbeta-induced miRNAs have sequence-predicted targets within the hepatitis C virus (HCV) genomic RNA. The introduction of synthetic miRNA-mimics corresponding to these IFNbeta-induced miRNAs reproduces the antiviral effects of IFNbeta on HCV replication and infection, whereas neutralization of these antiviral miRNAs with anti-miRNAs reduces the antiviral effects of IFNbeta against HCV. In addition, we demonstrate that IFNbeta treatment leads to a significant reduction in the expression of the liver-specific miR-122, an miRNA that has been previously shown to be essential for HCV replication. Therefore, our findings strongly support the notion that mammalian organisms too, through the interferon system, use cellular miRNAs to combat viral infections.
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              TLR3: interferon induction by double-stranded RNA including poly(I:C).

              Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA and its synthetic analog polyriboinosinic:polyribocytidylic acid (poly(I:C)) and induces type I interferon (IFN), inflammatory cytokine/chemokine production and dendritic cell (DC) maturation via the adaptor protein TICAM-1 (also called TRIF). TLR3 is expressed both intracellularly and on the cell surface of fibroblasts and epithelial cells, but is localized to the endosomal compartment of myeloid DCs. Several studies in TLR3-deficient mice demonstrate that TLR3 participates in the generation of protective immunity against some viral infections. Involvement of TLR3-TICAM-1 in activation of NK cells and CTLs by myeloid DCs suggests that TLR3 serves as an inducer of cellular immunity sensing viral infection rather than a simple IFN inducer. In this review, we summarize the current knowledge on TLR3 and discuss its possible role in innate and adaptive immunity.
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                Author and article information

                Contributors
                Journal
                Virology
                Virology
                Virology
                Elsevier Inc.
                0042-6822
                1096-0341
                20 January 2011
                15 March 2011
                20 January 2011
                : 411
                : 2
                : 288-305
                Affiliations
                Cell & Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, CA, 92182-4614, USA
                Author notes
                [* ]Corresponding author. Cell & Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, 5500 Campanile Drive; San Diego, CA 92182-4614, USA. Fax: +1 619 594 0777. rfeuer@ 123456sciences.sdsu.edu
                Article
                S0042-6822(10)00768-3
                10.1016/j.virol.2010.12.014
                3060663
                21251690
                20947464-471a-4fd9-9b51-92612d51e5e9
                Copyright © 2011 Elsevier Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 7 December 2010
                : 8 December 2010
                Categories
                Article

                Microbiology & Virology
                enteroviruses,cns
                Microbiology & Virology
                enteroviruses, cns

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