can autophagy cure herpes

Atg101, a novel mammalian autophagy protein interacting with Atg13. Boya, P., Reggiori, F. & Codogno, P. Emerging regulation and functions of autophagy. Cell. PubMed Central USA 106, 2084220846 (2009). Cell. Basal Autophagy Is Required for Herpes simplex Virus-2 Infection. 2023 May 23;23(1):201. doi: 10.1186/s12883-023-03239-x. A small heterogeneous cellular compartment enriched with sphingolipids and cholesterols. & Ou, J. H. HCV induces the expression of Rubicon and UVRAG to temporally regulate the maturation of autophagosomes and viral replication. HIV-1 virion infectivity factor (Vif) is targeted by histone deacetylase 6 (HDAC6) for degradation. Frontiers | JieZe-1 Alleviates HSV-2 Infection-Induced Genital Herpes It also selectively degrades immune components associated with viral particles. PLA2G16 represents a switch between entry and clearance of Picornaviridae. 1). Although macrophages infected with HSV-1 initially used the conventional MHC class I presentation pathway, a second pathway involving a vacuolar compartment was triggered later during infection. Dev. The https:// ensures that you are connecting to the Yang, Q. et al. Sergerie, Y., Rivest, S. & Boivin, G. Tumor necrosis factor-alpha and interleukin-1 beta play a critical role in the resistance against lethal herpes simplex virus encephalitis. The role of autophagy in genome stability through suppression of abnormal mitosis under starvation. Acad. 3). The cells were incubated with the virus in phosphate-buffered saline (PBS) supplemented with 0.1% glucose and 1% serum at 37C-5% CO2 conditions. In addition, autophagy-mediated exocytosis of antigens in vesicular compartments supports cross-presentation on MHC class I molecules. Additionally, NDP52 interacts through its galectin-interacting region with galectin 8, which binds to cytoplasmically exposed -galactoside glycans on pathogen-damaged endosomal membranes173. Very little is known about the role of autophagy in HSV-2 infection. Levine, B. PDF Basal Autophagy Is Required for Herpes simplex Virus-2 Infection Akhtar, J. Immunity. Thank you for visiting nature.com. Acad. Virol. Biochim. To counteract the antiviral role of EIF2AK2 and cellular autophagy, viral protein Us11 prevents EIF2AK2-mediated EIF2S1 phosphorylation. Nat. Eukaryotic cells deliver dangerous and unwanted cytoplasmic material to lysosomes for degradation via three major routes: microautophagy, chaperone-mediated autophagy (CMA) and macroautophagy3. Athanasiou E, Gargalionis AN, Anastassopoulou C, Tsakris A, Boufidou F. Brain Sci. Autophagy is a powerful tool that host cells use to defend against viral infection. 68, 765783 (2011). (c) Human foreskin fibroblasts were infected with HSV-2-GFP for 2hrs, followed by mock- or BFN-treatment. Autophagy, a cellular cleaning process, gets activated in response to certain types of metabolic stress, including nutrient deprivation, growth factor depletion and hypoxia. Blazquez, A. entirely supervised the project. CAS Second, using ATG5/ cells, we assessed the importance of autophagy for infection at various time points and under infection with various MOIs. Seino, J. et al. Autophagy 11, 906917 (2015). In infected macrophages, the interaction between HIV-1 and TLR8 and the Beclin 1-dependent dephosphorylation and nuclear translocation of transcription factor EB (TFEB) activates autophagy and lysosome biogenesis77. The Chinese herbal prescription JZ-1 induces autophagy to protect against herpes simplex Virus-2 in human vaginal epithelial cells by inhibiting the PI3K/Akt/mTOR pathway - PMC Back to Top Skip to main content An official website of the United States government Here's how you know The .gov means it's official. Takamura, A. et al. EBV nuclear antigen 1 (EBNA1) is the dominant CD4+ T cell antigen and is primarily processed in the autophagosome. TLR stimulation induces binding of MYD88 or TRIF to Beclin 1, which disrupts the Beclin 1B cell lymphoma-2 (BCL-2) interaction and ultimately activates autophagy (Fig. Lum, J. J., DeBerardinis, R. J. The Evolving Functions of Autophagy in Ocular Health: A Double-edged The cells were washed in PBS and imaged using Axiovert 100M fluorescence microscope (Zeiss). At 16 hpi, viral genomes were quantified by qPCR. Proc. Johnson, K. E., Chikoti, L. & Chandran, B. Microbe. During the preparation of this Review article, the authors were supported by grants from the US National Institutes of Health (CA200422, CA180779, DE023926, AI073099, AI116585 and AI129496) and the Fletcher Jones Foundation. This study reveals that autophagy occurs in pDCs and is required for recognition of viral infection and production of type I IFNs, highlighting the importance of autophagy in innate immunity against viral pathogenesis. 25, 110 (2013). As such, autophagy is shown to be able to directly capture the neuroattenuated ICP34.5-mutant HSV-1 virions or viral components, delivering them for lysosomal degradation and/or for the antigen presentation of viral peptides to the MHC-I/-II pathway for adaptive immune activation. Coxsackievirus B3 (CVB3) exits cells through autophagosomes that contain the exosome marker flotillin 1. 1). In antigen-presenting cells (APCs), autophagy delivers intracellular and extracellular antigens to the endolysosome, where they are loaded onto major histocompatibility complex (MHC) class II molecules for presentation to CD4+ T cells. Johnson, D. C. & Baines, J. D. Herpesviruses remodel host membranes for virus egress. and D.S. Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Mouse hepatitis virus (MHV) hijacks the LC3-coated EDEMsosome by accumulating endoplasmic reticulum (ER) degradation-enhancing -mannosidase-like protein 1 (EDEM1) and OS-9 in DMVs. Smed-Sorensen, A. et al. Viruses 3, 13321341 (2011). Orvedahl, A. et al. These results validated the autophagy-deficient nature of these cells. Cell. HSV-1 establishes virulence through inhibiting cellular autophagy22,23, or at least preventing its activation29, during infection. Biol. Autophagy 4, 524526 (2008). 4, 17531765 (1990). Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. PLoS One 10, e0124646; doi: 10.1371/journal.pone.0124646 (2015). Endogenous MHC class II processing of a viral nuclear antigen after autophagy. The cells were then harvested and lysed and the lysate was immunoblotted for p62 to assess autophagy flux. . 3). Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Influenza A virus infection of human primary dendritic cells impairs their ability to cross-present antigen to CD8 T cells. However, a recent study demonstrated that an ER transmembrane protein, SHISA5 (also known as SCOTIN), interacts with the viral non-structural protein 5A (NS5A), which leads to its autophagic degradation and suppresses viral replication41 (Fig. Binding to MYD88 or TRIF causes Beclin 1 to dissociate from the B cell lymphoma-2 (BCL-2) inhibitory complex, resulting in the induction of autophagy. James, S. H. & Kimberlin, D. W. Neonatal Herpes Simplex Virus Infection: Epidemiology and Treatment. McEwan, D. G. et al. Mercer, C. A., Kaliappan, A. Janus kinase-dependent activation of insulin receptor substrate 1 in response to interleukin-4, oncostatin M, and the interferons. The lipid kinase VPS34 creates phosphatidylinositol-3-phosphate (PtdIns3P)-rich regions on the surface of donor membranes, including the endoplasmic reticulum (ER), Golgi apparatus, ERmitochondria contact sites, endosomes and the plasma membrane154,155,156,157,158. 6a,b) or in human foreskin fibroblast cells (Fig. Dis. To monitor LC3-GFP punctae, confocal microscopy (Zeiss 710 microscope, Zeiss) was used. Nakatogawa, H., Ichimura, Y. Autophagy 5, 649662 (2009). volume16,pages 341354 (2018)Cite this article. Nat. In this study, an unknown mechanism of vaccine-mediated protection reveals that stress-response dependent initiation of autophagy enhances antigen presentation to T cells. Curr. Lamb, C. A., Yoshimori, T. & Tooze, S. A. The ATG16L complex is generated through a ubiquitin-like (UBL) conjugation reaction in which ATG12 is conjugated to ATG5 by the sequential action of ATG7 and ATG10 (ref.160). 24, 5868 (2014). HSV-1 and HSV-2 are closely related herpesviruses that rely on ICP34.5 protein as a major neurovirulence and neurotropism factor20,21. Infection that involves antibody-dependent enhancement induces the expression of ATG5 and ATG12 earlier in the infection process compared with direct DENV infection141. These results demonstrated that suppression of basal autophagy in host cells interferes with viral replication and the progress of infection. 21, 538547.e4 (2017). Gonzalez-Dosal, R. et al. Viruses interfere with autophagosome formation and fusion with the lysosome. Autophagy interaction with herpes simplex virus type-1 infection. This review article presents the relationships between autophagy and exocytosis and how viruses exit infected cells in packages wrapped into autophagic membranes. Article Recurrent Herpes Simplex Virus Type 1 (HSV-1) Infection Modulates Neuronal Aging Marks in In Vitro and In Vivo Models. Natl. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Article RUBCN, RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein; VPS, vacuolar protein sorting. 15, 239247 (2014). Treatment with prescription antiviral pills may be used for the following: Help sores heal during a first outbreak; Lower the frequency of recurrent outbreaks; Lessen the severity and duration of symptoms in recurrent outbreaks; Reduce the chance of passing the herpes virus to a partner Natl. Wong, J. et al. 8, 269 (2017). (c) Quantification of relative HSV-2 levels, from experiments performed as in (b). Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. (a and c). Inflammasomes induce maturation and secretion of proinflammatory cytokines50, which represent powerful antiviral effectors51,52,53. Nutrient starvation or rapamycin, which is an mTORC1 inhibitor, induces the formation of the active ULK1 complex, which ultimately phosphorylates and activates the Beclin 1VPS34 complex152,153. Future work is to determine the exact mechanism by which constitutive autophagic activity (or machinery) supports HSV infection. Furthermore, increasing evidence suggests that HSV-1 infection may constitute a gradual risk factor for neurodegenerative disorders. Paul, D. & Bartenschlager, R. Flaviviridae replication organelles: oh, what a tangled web we weave. An antiviral protein that is produced in the host and blocks viral replication. Cell 130, 165178 (2007). The site is secure. 84, 1211012124 (2010). Buckingham, E. M., Jarosinski, K. W., Jackson, W., Carpenter, J. E. & Grose, C. Exocytosis of varicella-zoster virus virions involves a convergence of endosomal and autophagy pathways. Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins. 6 Signs And Symptoms of Autophagy - Healthline ADS 2022 Jul 28;10(8):1817. doi: 10.3390/biomedicines10081817. A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. 11, 13551362 (2009). Rev. Ichimura, Y. et al. J. All authors wrote the article and reviewed and edited the manuscript before submission. 2f). Autophagy 10, 416430 (2014). Historical landmarks of autophagy research. In this study, lipid droplets and autophagic components associate during nutrient deprivation, and inhibition of autophagy increases triglyceride in lipid droplets, suggesting a critical function for autophagy in lipid metabolism. Autophagy could also limit inflammasome activity directly through targeting inflammatory cytokines such as IL-1 for autolysosomal degradation55. R01 AI073099/AI/NIAID NIH HHS/United States, R01 CA140964/CA/NCI NIH HHS/United States. & Levy, D. E. Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator. Human retinal pigment epithelial cell line (ARPE19), human foreskin fibroblasts and African green monkey foetal kidney epithelial (Vero) cells were provided by H. Ying (University of Illinois, Chicago, IL), N. Luraine (Rush University, Chicago, IL) and P. Spear (Northwestern University, Chicago, IL), respectively. How autophagy selectively identifies and sequesters lipid droplets remains unknown; however, lipid droplets that are targeted for degradation are decorated with LC3, similar to autophagosomes111. 2). In a comparative study testing various side effects of autophagy inhibitors, bafilomycin A1 (BFN), a well-known autophagy inhibitor that blocks fusion of autophagosomes with lysosomes35, was shown to have least nonspecific effects and no effect on mTOR activity, in treated cells in contrast to other agents tested34. The K7 protein of KSHV promotes RubiconBeclin 1 interaction and inhibits the enzymatic activity of VPS34, which blocks the fusion of autophagosomes with lysosomes75 (Fig. Cell. Rev. Nowag, H. et al. Zhirnov, O. P. & Klenk, H. D. Influenza A virus proteins NS1 and hemagglutinin along with M2 are involved in stimulation of autophagy in infected cells. Lee, H. K., Lund, J. M., Ramanathan, B., Mizushima, N. & Iwasaki, A. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Introduction. PLoS Pathog. Sci. Cell. Having observed low infection of cells deficient in autophagy, we sought to confirm quantitatively the effect of autophagy deficiency on viral levels in infected cells. Before using the ATG5/ cells in our virus assays, we wanted to validate their autophagy deficiency. Yordy, B., Tal, M. C., Hayashi, K., Arojo, O. Chauhan, S., Mandell, M. A. Cell. Pathog. Shi, J. et al. Validation of autophagy deficiency in ATG5/ cells. Immunity in latent Herpes simplex virus infection. FOIA PLoS Biol. However, it is unclear how this trafficking is coordinated. Cell. PLoS. 2). To antagonize autophagy, -herpesviruses, including Kaposis sarcoma-associated herpesvirus (KSHV) and murine -herpesvirus 68 (MHV68), have viral homologues of BCL-2, ORF16 and M11 (ref.69). A key component of the cellular membrane fusion machinery that mediates vesicular fusion events in autophagosomelysosome fusion. 17, 300310 (2015). USA 102, 79227927 (2005). Autophagy 4, 276279 (2008). Horseradish peroxidase-conjugated secondary (anti-rabbit) antibodies were purchased from Jackson Immunoresearch (Catalog number 111-005-144). The matrix protein of human parainfluenza virus type 3 induces mitophagy that suppresses interferon responses. Virology. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/, Yakoub, A., Shukla, D. Basal Autophagy Is Required for Herpes simplex Virus-2 Infection. Initially, the induction of autophagy during flavivirus infections was thought to be a consequence of the ER stress-derived UPR. Human corneal epithelial (HCE) cells were a kind gift from K. Hayashi (National Eye Institute, Bethesda, MD). Kaposis sarcoma-associated herpesvirus (KSHV) expresses another host protein homologue, vFLIP, that prevents autophagy protein 3 (ATG3) from processing LC3 during phagosome elongation. J. Biol. & Roizman, B. Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Inhibition of herpes simplex virus infection by oligomeric stilbenoids through ROS generation. Nature 441, 885889 (2006). Induced and basal autophagy may serve distinct functions and their dysregulation causes morbidities and mortalities19,71,72 and influences susceptibility to various pathogens73,74. ROS may induce NALP3 inflammasomes61, type-I IFN responses62, or cytokine production in response to infection63. Analysis of FACS data was performed using Summit software (Beckman Coulter). Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Why Fasting Causes Autophagy, and What That Means for Your Health Rev. Additionally, cGAS-dependent signalling induces autophagy, which promotes pathogen clearance and functions as a negative feedback loop to turn off signalling. Using HSV-2-GFP virus, we monitored the progress of infection microscopically. An enzyme catalysing transfer of ubiquitin from the activated site of an E2 enzyme to a primary amine on a lysine side chain or amino terminus of a protein. HCV-induced autophagosomes comprise caveolin 1, caveolin 2 and annexin A2, which promote HCV assembly. As discussed above, picornaviruses accumulate autophagic membranes to support their viral replication and release. PLoS. For example, HSV-2 ICP34.5 gene, contrary to HSV-1 ICP34.5, contains an intron and undergoes alternative splicing, yielding various structurally unique splice-variants27 and protein products28. The removal of these components by selective autophagy is crucial for cellular homeostasis. The autophagic machinery was first described in yeast, and homologues were found in mammals. Further, poliovirus infection led to the accumulation of LC3 in puncta, and the expression of the viral proteins 2BC and 3A led to LC3 lipidation and DMV formation, which provides a mechanistic link between autophagy and poliovirus replication (Fig. When CVB3-infected cells were treated with inhibitors of autophagosome maturation, virion production was increased and p62 protein levels remained unchanged82, suggesting that viral replication increases the generation of autophagic membrane structures without progression to lysosomal degradation. 1. Moreover, suckling and non-suckling ATG7/ mice all died at the same time, within 1 day of birth38, suggesting that the reason of death is not due to nutrient deprivation and that it may be due to disruption of a cellular function performed by basal autophagy. Natl. Overexpression of UVRAG was shown to suppress HCV replication. (b) Quantification of the number of LC3 punctae per cells, from confocal microscopy experiments performed as in (a). The poliovirus proteins 2BC and 3A increase LC3 lipidation and DMV formation. genital ulcers and inflammation) and psychosocial problems3,4. Nature 288, 288290 (1980). PLoS Pathog. J. Virol. PubMed Central Cell 132, 2742 (2008). Proc. There are many factors leading to the induction and resolution of xenophagy, necessitating clear experimental metrics to confirm xenophagy during viral infections. 2, 289310 (2015). McLauchlan, J. Lipid droplets and hepatitis C virus infection. Article HSV-2 primarily causes severe genital diseases associated with physical disorders (e.g. "Autophagy" literally translates to "self-eating", and while the term self-eating is a little unnerving, it's a good thing for your body to eat some cells. Up to four distinct polypeptides are produced from the 34.5 open reading frame of herpes simplex virus 2. Quantification figures show mean values and error bars represent standard error of the mean. Cells use autophagy to get rid of damaged proteins and organelles, to . Cell. Cell 165, 867881 (2016). Biol. Mathew, S. S., Della Selva, M. P. & Burch, A. D. Modification and reorganization of the cytoprotective cellular chaperone Hsp27 during herpes simplex virus type 1 infection. J. Virol. 11, 298305 (2012). 16 When symptoms subside, HSV-1 retreats to nearby neurons, most commonly the trigeminal gangl. Viral DNA was quantified via quantitative PCR (qPCR) on an ABI 7500 Fast thermocycler (Applied Biosystems), using HSV-specific primers (Forward 5-TAC AAC CTG ACC ATC GCT TG-3, Reverse 5-GCC CCC AGA GAC TTG TTG TA-3) which amplify the glycoprotein D (gD) gene of HSV-2. Buckingham, E. M., et al. Hofstetter, A. M., Rosenthal, S. L. & Stanberry, L. R. Current thinking on genital herpes. J. Virol. (a) Validation of autophagy suppression by BFN treatment: HCE cells were mock-treated or treated with BFN for 16hours. Regulation of autophagic activation by Rta of Epstein-Barr virus via the extracellular signal-regulated kinase pathway. SMURF1 and FANCC also target HSV-1 for virophagy, suggesting that those two proteins commonly function as virophagic factors35,36. Clipboard, Search History, and several other advanced features are temporarily unavailable. Deretic, V., Saitoh, T. & Akira, S. Autophagy in infection, inflammation and immunity. To further confirm, we determined virus levels in the cells via qPCR virus genome quantification. The autophagy pathway and its interaction with HSV-1. Kraft, C., Deplazes, A., Sohrmann, M. & Peter, M. Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Romao, S., Gannage, M. & Munz, C. Checking the garbage bin for problems in the house, or how autophagy assists in antigen presentation to the immune system. Perhaps, impairment in autophagy-deficient cells of intracellular endosomal trafficking of viral, or infection-regulating cellular, components participates to infection suppression in these cells. Looker, K. J., Garnett, G. P. & Schmid, G. P. An estimate of the global prevalence and incidence of herpes simplex virus type 2 infection. 3), and disruption of the M2LC3 interaction decreases virion budding and stability. Curr. Platanias, L. C., Uddin, S., Yetter, A., Sun, X. J. HSV-2 strain G was provided by P. Spear (Northwestern University, Chicago, IL). A subset of dendritic cells that are distinct from conventional dendritic cells and that produce large amounts of interferon. Collectively, hosts attempt to balance the induction of autophagy to avoid viral infection and pathogenesis. Recently, the CD8+ T cell-specific antigens of HCMV 65kDa phosphoprotein (pp65) were shown to be cross-presented by human B cells through a pathway involving autophagosomes rather than the TAP-dependent conventional secretory pathway60 (Fig. Biol. Immune cells found in the epidermis that function as antigen-presenting cells that bind antigens entering through the skin. 2021 Dec 27;23(1):242. doi: 10.3390/ijms23010242. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Numerous medically infectious pathogens are degraded by autophagy, such as group A Streptococcus, herpes simplex virus type I (HSV-1), Listeria monocytogenes, . UL138 from human cytomegalovirus (HCMV) and gB from HSV-1 are presented on MHC class I molecules in an autophagy-dependent pathway, when antigen peptide transporter (TAP)-dependent presentation is blocked. To be or not to be? Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. (SNARE). Second, autophagosomal inclusion of the virus might support a step in the viral life cycle such as using the vesicle membranes for viral envelopment46,47,48. & Reggiori, F. Are nidoviruses hijacking the autophagy machinery? The second envelope originates from ER and Golgi apparatus membranes, and at the cell surface, this outer membrane fuses with the plasma membrane121. 7, e1002422 (2011). Second, they chose different strains of harmless . Autophagy is involved in influenza A virus replication. PubMed Central Autophagy is involved in various physiological processes, including starvation, cell differentiation and development, and degradation of aberrant structures, which ultimately maintains cellular homeostasis9. Opin. (d) Quantification of the relative p62 levels in (c), after normalization to GAPDH. 19, 663671 (2016). Google Scholar. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Life Sci. Pathog. Cell. Most people with . 6, e1876 (2015). Burfoot, M. S. et al. As mentioned before, the KSHV vFLIP and vBCL-2 target ATG3 and Beclin 1, respectively, and these interactions block autophagosome formation and vesicle nucleation, thereby supporting KSHV replication and disease progression. TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively regulates TLR3/4-mediated innate immune responses. At this stage, the Beclin 1VPS34 complex is identifiable by the presence of ultraviolet radiation resistance-associated gene protein (UVRAG) instead of ATG14L149. J. Virol. Wang, L., Tian, Y. It's a natural process of cellular repair and cleaning. Funct. 2d,e). 90, 13831435 (2010). (a) LC3-GFP-expressing WT or ATG5/ MEFs were cultured in regular serum-containing medium (Fed), or starved for 3hr. Autophagy regulates lipid metabolism. 17, 243246 (2004). For example, virions can be released from the cell via fusion of the lysosomes with the plasma membrane46. Biol. Degradation of misfolded proteins, cellular differentiation, and defence against pathogens are several of the functions of autophagy . Microautophagy of cytosolic proteins by late endosomes. Natl. Autophagy can also contribute to antigen presentation when TAP is inhibited. Cornea 20, 113 (2001). Basal autophagy takes place at low or modest levels under normal conditions and regardless of the feeding conditions, as in embryogenesis44. An average of 50 cells was assessed and used for counting. Autophagy also contributes to the delivery and processing of extracellular antigens for cross-presentation by MHC class I molecules in a cell-specific manner59,60,61. During hepatitis C virus (HCV) infection, the host endoplasmic reticulum (ER) transmembrane protein SCOTIN associates with HCV non-structural protein 5A (NS5A) and leads to its degradation, restricting HCV replication. (UPR). 9, e110655 (2014). Biol. 38, 533537 (2011). 49, 383391 (2010). How To Get Rid Herpes Virus with Autophagy Fasting? HSV-1 virus was shown to establish virulence via preventing launch of an autophagic response to infection, as HSV-1 ICP34.5 binds to and inhibits the autophagy mediator beclin122,23,24,25. For possible reasons for the contribution of basal autophagy to infection, some scenarios may be proposed based on lessons learned from other viruses. J. Genet. ARF, ADB ribosylation factor 1; GBF1, Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1; IRS1, insulin receptor substrate 1; MHV68, murine -herpesvirus 68; PAS, pre-autophagosomal structure; PI3K, phosphoinositide 3-kinase; PtdIns3P, phosphatidylinositol-3-phosphate; Ub, ubiquitin; VPS34, vacuolar protein sorting 34; WIPI, WD-repeat domain phosphoinositide-interacting protein. EBioMedicine 1, 116125 (2014). Sci. The human cytomegalovirus protein TRS1 inhibits autophagy via its interaction with Beclin 1. PubMedGoogle Scholar. Cell Host Microbe 12, 334345 (2012). Herpes Simplex Virus and Interferon Signaling Induce Novel Autophagic Clusters in Sensory Neurons. Cell biology of lipid droplets. Lancet 357, 15131518 (2001). Science 339, 786791 (2013). Proc. Science 333, 228233 (2011). Ravikumar, B., Moreau, K., Jahreiss, L., Puri, C. & Rubinsztein, D. C. Plasma membrane contributes to the formation of pre-autophagosomal structures. Thus we monitored autophagy flux in cells during HSV-2 infection using sequestosome1 (or p62) immunoblotting. Pathog. PubMed USA 110, 1204812053 (2013). Acad. Furthermore, the viral protease NS3 cleaves reticulophagy regulator 1 (FAM134B) to block reticulophagy so that ZIKV can use the ER as a replication site. Korom, M., Davis, K. L. & Morrison, L. A. 22, 10471059 (2016). HSV-2 (strain 333) and HSV-2 (333)-GFP viruses were provided by J. Vieira (University of Washington). Acta. Autophagy is a powerful tool that host cells use to defend against viral infection. In autophagy-deficient cells, adding exogenous free fatty acids rescues DENV replication, but the drug etomoxir, which prevents the transport of fatty acids into the mitochondria, blocks this process115. Cell Death Differ. Sci. Viruses that are associated with cancer development, including EBV, hepatitis B virus (HBV), HCV and KSHV, have evolved multiple strategies to avoid autophagy-mediated elimination, which can facilitate tumour progression.
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