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      Manipulation of autophagy by (+) RNA viruses

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          Abstract

          Autophagy is an evolutionarily conserved process central to host metabolism. Among its major functions are conservation of energy during starvation, recycling organelles, and turnover of long-lived proteins. Besides, autophagy plays a critical role in removing intracellular pathogens and very likely represents a primordial intrinsic cellular defence mechanism. More recent findings indicate that it has not only retained its ability to degrade intracellular pathogens, but also functions to augment and fine tune antiviral immune responses. Interestingly, viruses have also co-evolved strategies to manipulate this pathway and use it to their advantage. Particularly intriguing is infection-dependent activation of autophagy with positive stranded (+)RNA virus infections, which benefit from the pathway without succumbing to lysosomal degradation. In this review we summarise recent data on viral manipulation of autophagy, with a particular emphasis on +RNA viruses and highlight key unanswered questions in the field that we believe merit further attention.

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          Most cited references71

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          Autophagy in cell death: an innocent convict?

          The visualization of autophagosomes in dying cells has led to the belief that autophagy is a nonapoptotic form of programmed cell death. This concept has now been evaluated using cells and organisms deficient in autophagy genes. Most evidence indicates that, at least in cells with intact apoptotic machinery, autophagy is primarily a pro-survival rather than a pro-death mechanism. This review summarizes the evidence linking autophagy to cell survival and cell death, the complex interplay between autophagy and apoptosis pathways, and the role of autophagy-dependent survival and death pathways in clinical diseases.
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            Lysosomes and autophagy in cell death control.

            Lysosomal hydrolases participate in the digestion of endocytosed and autophagocytosed material inside the lysosomal/autolysosomal compartment in acute cell death when released into the cytosol and in cancer progression following their release into the extracellular space. Lysosomal alterations are common in cancer cells. The increased expression and altered trafficking of lysosomal enzymes participates in tissue invasion, angiogenesis and sensitization to the lysosomal death pathway. But lysosomal heat-shock protein 70 locally prevents lysosomal-membrane permeabilization. Similarly, alterations in the autophagic compartment are linked to carcinogenesis and resistance to chemotherapy. Targeting these pathways might constitute a novel approach to cancer therapy.
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              Autophagy during viral infection — a double-edged sword

              Autophagy is a powerful tool that host cells use to defend against viral infection. Double-membrane vesicles, termed autophagosomes, deliver trapped viral cargo to the lysosome for degradation. Specifically, autophagy initiates an innate immune response by cooperating with pattern recognition receptor signalling to induce interferon production. It also selectively degrades immune components associated with viral particles. Following degradation, autophagy coordinates adaptive immunity by delivering virus-derived antigens for presentation to T lymphocytes. However, in an ongoing evolutionary arms race, viruses have acquired the potent ability to hijack and subvert autophagy for their benefit. In this Review, we focus on the key regulatory steps during viral infection in which autophagy is involved and discuss the specific molecular mechanisms that diverse viruses use to repurpose autophagy for their life cycle and pathogenesis.
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                Author and article information

                Contributors
                Journal
                Semin Cell Dev Biol
                Semin. Cell Dev. Biol
                Seminars in Cell & Developmental Biology
                Academic Press
                1084-9521
                1096-3634
                8 August 2019
                8 August 2019
                :
                Affiliations
                [a ]HKU-Pasteur Research Pole, School of Public Health, University of Hong Kong, Hong Kong
                [b ]School of Biomedical Sciences, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
                Author notes
                [* ]Corresponding author at: HKU-Pasteur Research Pole, School of Public Health, University of Hong Kong, Hong Kong. sanyal@ 123456hku.hk
                Article
                S1084-9521(18)30222-2
                10.1016/j.semcdb.2019.07.013
                7102625
                31382014
                c7d388ab-7470-40b4-8710-d7df7ac5f8d2
                © 2019 Elsevier Ltd. 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
                : 21 March 2019
                : 11 June 2019
                : 30 July 2019
                Categories
                Article

                Developmental biology
                autophagy,positive stranded rna virus,viral subversion strategies
                Developmental biology
                autophagy, positive stranded rna virus, viral subversion strategies

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