autophagy and virusesautophagy and viruses

There is growing evidence that host cells try to control Herpesvirus infections by activating the autophagic machinery. Autophagy is induced and supports virus replication in HHS Vulnerability Disclosure, Help However, because rapamycin also targets pathways other than autophagy, it is difficult to isolate the role of autophagy stimulation in its therapeutic action. Autophagy can rapidly provide fuel for energy and building blocks for renewal of cellular components, and is therefore essential for the cellular response to starvation and other types of stress. HSV-1 US11 protein inhibits autophagic signaling through inhibition of PKR. Bethesda, MD 20894, Web Policies Hakki M, Marshall EE, De Niro KL, Geballe AP. PSMB1 Inhibits the Replication of Porcine Reproductive and Respiratory 8600 Rockville Pike Mercer CA, Kaliappan A, Dennis PB. Frontiers | Autophagy Modulation by Viral Infections Influences Tumor Some autophagy proteins are targeted by Herpesvirus-encoded proteins. PKR is a key player in the antiviral action of interferon, and many viruses express proteins that antagonize the PKR signaling pathway [39]. As intracellular parasites, during the course of an infection, viruses encounter autophagy and interact with the proteins that execute this process. Autophagy regulates various cellular processes, and defective autophagy often translates into pathological situations [ 4]. Several results indicate that these proteins are essential for -Herpesvirus pathogenesis, but so far M11 is the only -herpesvirus Bcl-2 homolog that has definitely been shown to play a role during infection in vivo [93]. Analysis of the role of autophagy in replication of herpes simplex virus in cell culture. The Us11 protein is a double-stranded RNA binding protein, expressed with late kinetics, which can antagonize PKR either by a direct interaction or by interacting with PACT, an activator of PKR [64,66]. These findings show that the ICP34.5/Beclin 1 interaction, and consequently the inhibition of autophagy by ICP34.5 might be another factor that contributes to viral neurovirulence, independently of the role of ICP34.5 in antagonizing host cell shutoff. Yla-Anttila P, Vihinen H, Jokitalo E, Eskelinen EL. Talloczy et al. The definition of autophagy is "consumption of the body's own tissue as a metabolic process occurring in starvation and certain diseases." Researchers believe that autophagy is a survival mechanism, or a way that the body cleverly responds to stress in order to protect itself. Kyei GB, Dinkins C, Davis AS, Roberts E, Singh SB, Dong C, Wu L, Kominami E, Ueno T, Yamamoto A, Federico M, Panganiban A, Vergne I, Deretic V. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. As a consequence, many viruses have developed strategies to counteract virus-induced apoptosis. Many of the known virus-encoded activators of autophagic signaling, and in some cases active autophagy, are listed, although the mechanisms of activation are poorly understood. HHS Vulnerability Disclosure, Help As a library, NLM provides access to scientific literature. However, autophagy can also be induced in response to cellular stresses such as nutrient deprivation, the unfolded protein response (UPR), or oxidative stress [ 6 ]. Epub 2016 Mar 10. FLIP interacts with the E2-like enzyme Atg3 and represses autophagy by preventing the binding of Atg3 to LC3. Fasting is defined as abstinence from foods, drinks, or both for a period of time. Foot-and-mouth disease virus structural protein VP3 interacts with Single autophagy proteins or cassettes of the core autophagy machinery can also function as antiviral factors independently of the . Bookshelf Gangappa S, van Dyk LF, Jewett TJ, Speck SH, Virgin HWt. In HSV-1 infected macrophages, the glycoprotein gB is processed both through the classical MHC class I presentation pathway involving the proteasome (B) and through a vacuolar pathway involving autophagy and partially lysosomal digestion. Federal government websites often end in .gov or .mil. Furthermore, the neurovirulence of Beclin 1-binding-deficient ICP34.5 HSV-1 was fully restored in PKR/ mice, suggesting that PKR is connected to Beclin 1 in the regulation of autophagy. Epub 2022 Oct 27. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). As with several other RNA viruses, coronaviruses have long been known to interact with the cellular macroautophagy/autophagy (hereafter autophagy) pathway to promote their replication [Citation 30, Citation 31].Autophagy is a conserved cellular process involving the formation of autophagosomes which enclose cytoplasmic cargo, including long-lived proteins, protein aggregates and . Cassady KA, Gross M, Roizman B. Now appreciated as a constitutive degradative mechanism that promotes cellular homeostasis, autophagy is also required for a variety of developmental processes, cellular stress responses, and immune pathways. Organization of the pre-autophagosomal structure responsible for autophagosome formation. vFLIP (HHV8, MH68) inhibits autophagy by interacting with Atg3. Interactions between Autophagy and DNA Viruses. - SciSpace by Typeset Autophagy happens as a result of cellular stressors, such as nutrient deprivation from fasting, exercise, or significant temperature change. HHV-6, which belongs to the Roseolovirus genus of the Herpesvirus subfamily, is related to HHV-7 and, to a lesser extent, to HCMV. In this review, we summarized the virus regulation of autophagy, the effect of autophagy on virus replication, and the mechanisms involved in virus-autophagy interaction. VZV is in fact known to remain highly cell-associated in cell cultures, and enveloped virions accumulate in acidic cytoplasmic vacuoles other than lysosomes, which means that autophagy might limit viral production by trapping viral particles in the autophagosomal pathway. Interestingly this stimulation of autophagy has also been corroborated by in vivo data, since LC3 was expressed abundantly in infected cells taken from biopsies of zoster vesicles. Chaumorcel M, Souquere S, Pierron G, Codogno P, Esclatine A. Similarly, several factors such as DAP kinase, TRIF or MyD88 (myeloid differentiation factor 88), and BNIP3, which are activated by death signals, pathogens and hypoxia, respectively, enhance autophagy by reducing/disrupting the Beclin 1/Bcl-2 interaction [28,33,34]. Ganley IG, Lam du H, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. Liu Y, Schiff M, Czymmek K, Talloczy Z, Levine B, Dinesh-Kumar SP. The precise mechanisms involved in the inhibition of autophagy by HCMV are still unclear. Subsequently, the Bcl-2 homolog of HV68 was also reported to inhibit autophagy by interaction with Beclin 1 [86,87]. Deretic V, Levine B. Autophagy, immunity; microbial adaptations. Shown are selected examples of, Proviral functions of autophagy-related genes, Proviral functions of autophagy-related genes in viral infection. Autophagy: Definition, Process, Fasting & Signs The autophagy-inhibitory-complex formed by cellular Bcl-2 and Beclin-1 can be modulated by nutrient conditions, whereas viral Bcl-2 forms a stable association with Beclin-1, which results in a constant repression of autophagy [31]. The goal of this review is to summarize, in brief, what we know so far about the relationship between autophagy and viruses, particularly for those who are not familiar with the field. The way autophagy contributes to the antiviral innate immune response in the context of HSV-1 infections is still puzzling. The Beclin 1:hVps34 complex is also modulated by the recruitment of positive and negative regulators, by post-translational modifications of Beclin 1 [28], and by microRNA as recently reported [29]. Clipboard, Search History, and several other advanced features are temporarily unavailable. Ozaki KS, Camara NO, Nogueira E, Pereira MG, Granato C, Melaragno C, Camargo LF, Pacheco-Silva A. Several viral proteins, such as ICP34.5 (HSV-1) or vBcl-2 (HHV-8), have been shown to interact with Beclin 1, leading to the inhibition of autophagy, and will be discussed later in this review [36]. Autophagy is a highly conserved intracellular degradation process that targets protein aggregates and damaged organelles. 2021 Jun 24;26(1):29. doi: 10.1186/s11658-021-00272-x. When autophagy meets viruses: a double-edged sword with functions in defense and offense. sharing sensitive information, make sure youre on a federal Endogenous MHC class II processing after autophagy has also been reported for other proteins, complement C5, Mucin 1 oncoprotein and a bacterial antigen neomycin phosphotransferase [83]. However, lower steady state levels of p62 indicate higher levels of active autophagic degradation. Talloczy Z, Jiang W, Virgin HWt, Leib DA, Scheuner D, Kaufman RJ, Eskelinen EL, Levine B. Pattingre et al. Abstract Autophagy is an evolutionarily conserved catabolic cellular process that exerts antiviral functions during a viral invasion. Autophagy regulates programmed cell death during the plant innate immune response. Macroautophagy (referred to as autophagy below) involves the formation of a double membrane-bound vacuole, known as an autophagosome, which ultimately fuses with the lysosomal compartment to degrade the sequestered material [1]. Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. Some viruses have been shown to have developed diverse tactics to antagonize the host cells autophagic defense. However to date, EBNA1 is the only viral antigen known to be presented on MHC class II via the autophagic pathway. Schmid D, Munz C. Innate and adaptive immunity through autophagy. Degradation of both structural and non structural viral proteins is enhanced in the context of unrestrained autophagy, but it is not necessarily correlated with the degradation of entire HSV-1 particles [44]. The ability of xenophagy to capture and eliminate new incoming HSV-1 virions therefore remains to be demonstrated. Autophagy. The most common include ( 1, 2, 3, 4 ): Absolute fasting: not eating or drinking. FIGURE 1: Possible protective mechanisms of autophagy against coronaviruses. Taken together these data suggest that the modulation of autophagy by HSV-1 could be either cell-type dependent and/or time dependent. Yu JW, Shi Y. FLIP and the death effector domain family. Cells. The .gov means its official. Autophagy and viruses: adversaries or allies? Single autophagy proteins or cassettes of the core autophagy machinery can also function as antiviral factors independently of the canonical autophagy pathway. Lee DY, Sugden B. Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, Herman B, Levine B. Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nothing is yet known about the interplay between autophagy and the lytic cycle of EBV, but at least two latent antigens, EBNA 1 and LMP1, are known to activate or to interfere with the autophagic machinery [48,80]. Under these conditions, the upregulation of autophagy enables the cell to survive by providing amino acids and energy, by clearing damaged proteins and organelles, and by eliminating intracellular pathogenic microbes via a process known as xenophagy. Before In this review, we focus on the importance of these pathways in the arbovirus replication and infection processes. However, during the late phase of macrophage infection, HSV-1 stimulates autophagosome formation. Dengue virus manipulates lipid metabolism for viral replication via lipophagy. The https:// ensures that you are connecting to the Bethesda, MD 20894, Web Policies Relationships between Herpesvirus and autophagy. Autophagy is also involved in the adaptative immune responses to microorganisms infection, for example by providing viral endogenous antigens for loading onto major histocompatibility complex (MHC) class I and class II in order to activate the adaptive immunity [4749]. The site is secure. Autophagy plays an important role when it comes to aging and longevity, too. However, co-evolution and co-adaptation between viruses and autophagy have armed viruses with multiple strategies to subvert the autophagic machinery and counteract cellular antiviral responses. Taken together, these data show that HSV-1 infection activates PKR and stimulates autophagy, but that the expression of ICP34.5 allows the virus to block PKR signaling and so to antagonize the induction of autophagy (Figure 1). official website and that any information you provide is encrypted TSC2 is a GTPase-activating protease acting on Rheb, which in its inactive GDP-form disassembles from mTORC1, resulting in its inactivation [25]. The autophagic machinery and its regulation pathways. Apoptosis, autophagy and the unfolded protein response (UPR) are three mechanisms that are involved in pathogenesis of many viruses. Delgado MA, Elmaoued RA, Davis AS, Kyei G, Deretic V. Toll-like receptors control autophagy. BHRF1 of Epstein-Barr virus, which is homologous to human proto-oncogene bcl2, is not essential for transformation of B cells or for virus replication. In response, viruses have evolved means to resist, escape, or subvert the autophagic process. Contribution of autophagy to adaptative immunity against Herpesviruses. Swine acute diarrhea syndrome coronavirus induces autophagy to promote its replication via the Akt/mTOR pathway. Several recent reviews address the interplay between viruses and autophagy [39,42,43]. Jackson WT, Giddings TH, Jr, Taylor MP, Mulinyawe S, Rabinovitch M, Kopito RR, Kirkegaard K. Subversion of cellular autophagosomal machinery by RNA viruses. HSV-1 is known to be able to antagonize the host autophagy response in fibroblasts [38], in primary murine neurons [44], and in macrophages [47]. However, a few cases have also been documented, in which Herpesviruses are not able to inhibit autophagy [47,57]. Front Cell Infect Microbiol. More remarkably, the same viral protein (HSV-1 ICP34.5) prevents the induction of autophagy by two different routes.