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      Virus Control of Cell Metabolism for Replication and Evasion of Host Immune Responses

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          Abstract

          Over the last decade, there has been significant advances in the understanding of the cross-talk between metabolism and immune responses. It is now evident that immune cell effector function strongly depends on the metabolic pathway in which cells are engaged in at a particular point in time, the activation conditions, and the cell microenvironment. It is also clear that some metabolic intermediates have signaling as well as effector properties and, hence, topics such as immunometabolism, metabolic reprograming, and metabolic symbiosis (among others) have emerged. Viruses completely rely on their host's cell energy and molecular machinery to enter, multiply, and exit for a new round of infection. This review explores how viruses mimic, exploit or interfere with host cell metabolic pathways and how, in doing so, they may evade immune responses. It offers a brief outline of key metabolic pathways, mitochondrial function and metabolism-related signaling pathways, followed by examples of the mechanisms by which several viral proteins regulate host cell metabolic activity.

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          Most cited references102

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          Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1.

          Neutrophils contribute to pathogen clearance by producing neutrophil extracellular traps (NETs), which are genomic DNA-based net-like structures that capture bacteria and fungi. Although NETs also express antiviral factors, such as myeloperoxidase and α-defensin, the involvement of NETs in antiviral responses remains unclear. We show that NETs capture human immunodeficiency virus (HIV)-1 and promote HIV-1 elimination through myeloperoxidase and α-defensin. Neutrophils detect HIV-1 by Toll-like receptors (TLRs) TLR7 and TLR8, which recognize viral nucleic acids. Engagement of TLR7 and TLR8 induces the generation of reactive oxygen species that trigger NET formation, leading to NET-dependent HIV-1 elimination. However, HIV-1 counteracts this response by inducing C-type lectin CD209-dependent production of interleukin (IL)-10 by dendritic cells to inhibit NET formation. IL-10 suppresses the reactive oxygen species-dependent generation of NETs induced upon TLR7 and TLR8 engagement, resulting in disrupted NET-dependent HIV-1 elimination. Therefore, NET formation is an antiviral response that is counteracted by HIV-1. Copyright © 2012 Elsevier Inc. All rights reserved.
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            A giant virus in amoebae.

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              Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling.

              The evolutionarily conserved serine-threonine kinase mammalian target of rapamycin (mTOR) plays a critical role in regulating many pathophysiological processes. Functional characterization of the mTOR signaling pathways, however, has been hampered by the paucity of known substrates. We used large-scale quantitative phosphoproteomics experiments to define the signaling networks downstream of mTORC1 and mTORC2. Characterization of one mTORC1 substrate, the growth factor receptor-bound protein 10 (Grb10), showed that mTORC1-mediated phosphorylation stabilized Grb10, leading to feedback inhibition of the phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated, mitogen-activated protein kinase (ERK-MAPK) pathways. Grb10 expression is frequently down-regulated in various cancers, and loss of Grb10 and loss of the well-established tumor suppressor phosphatase PTEN appear to be mutually exclusive events, suggesting that Grb10 might be a tumor suppressor regulated by mTORC1.
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                Author and article information

                Contributors
                URI : http://loop.frontiersin.org/people/83525/overview
                URI : http://loop.frontiersin.org/people/679817/overview
                URI : http://loop.frontiersin.org/people/227230/overview
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                18 April 2019
                2019
                : 9
                : 95
                Affiliations
                [1] 1Laboratorio de Inmunorregulación, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional , Mexico City, Mexico
                [2] 2School of Health Sciences, University of Portsmouth , Portsmouth, United Kingdom
                Author notes

                Edited by: Jonatas Abrahao, Federal University of Minas Gerais, Brazil

                Reviewed by: Rafael Elias Marques, Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Brazil; Mauricio Teixeira Lima, Federal University of Minas Gerais, Brazil

                *Correspondence: María Maximina B. Moreno-Altamirano bertha.moreno.altamirano@ 123456gmail.com
                Francisco Javier Sánchez-García fsanchez_1@ 123456yahoo.co.uk

                This article was submitted to Virus and Host, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2019.00095
                6482253
                31058096
                081e5755-0243-4db5-8863-e71390fd415c
                Copyright © 2019 Moreno-Altamirano, Kolstoe and Sánchez-García.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 January 2019
                : 22 March 2019
                Page count
                Figures: 2, Tables: 5, Equations: 0, References: 161, Pages: 15, Words: 12410
                Funding
                Funded by: Consejo Nacional de Ciencia y Tecnología 10.13039/501100007350
                Categories
                Cellular and Infection Microbiology
                Review

                Infectious disease & Microbiology
                viruses,cell metabolism,mitochondria,immune response,viral evasion

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