Viral strategies for the evasion of immunogenic cell death (original) (raw)
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To kill or be killed: how viruses interact with the cell death machinery
Journal of Internal Medicine, 2010
A virus (from the Latin virus meaning toxin or poison) is a small infectious agent that can only replicate inside the cells of another organism. Viruses are found wherever there is life and have probably existed since living cells first evolved. Viruses do not have their own metabolism and require a host cell to make new products. The range of structural and biochemical (i.e., cytopathic) effects that viruses have on the host cell is extensive. Most viral infections eventually result in the death of the host cell. The causes of death include cell lysis, alterations to the cell's surface membrane and various modes of programmed cell death. Some viruses cause no apparent changes to the infected cell. Cells in which the virus is latent and inactive show few signs of infection and often function normally. This causes persistent infection and the virus is often dormant for many months or years. Some viruses can cause cells to proliferate without causing malignancy, whereas others are established causes of cancer. Human organisms use a genetically controlled cell death programme that prevents the spreading of viral infection and kills the virus. Between 19 and 21 November 2009, with sponsorship from the Journal of Internal Medicine, the Swedish Research Foundation and the Swedish Cancer Society hosted a conference in Stockholm entitled: 'To kill or to be killed. Viral evasion strategies and interference with cell death machinery'. Four comprehensive reviews from this conference are presented in this issue of the Journal of Internal Medicine. These reviews include descriptions of: the modulation of host innate and adaptive immune defenses by cytomegalovirus; the impact of gammachain family cytokines on T cell homoeostasis in HIV-1 infection and the therapeutic implications; approaches to killing tumours by depriving them of the mechanisms for detoxification; and viral strategies for the evasion of immunogenic cell death.
Viral strategies for evading antiviral cellular immune responses of the host
Journal of Leukocyte Biology, 2005
The host invariably responds to infecting viruses by activating its innate immune system and mounting virus-specific humoral and cellular immune responses. These responses are aimed at controlling viral replication and eliminating the infecting virus from the host. However, viruses have evolved numerous strategies to counter and evade host's antiviral responses. Providing specific examples from the published literature, we discuss in this review article various strategies that viruses have developed to evade antiviral cellular responses of the host. Unraveling these viral strategies allows a better understanding of the hostpathogen interactions and their coevolution. This knowledge is important for identifying novel molecular targets for developing antiviral reagents. Finally, it may also help devise new knowledgebased strategies for developing antiviral vaccines.
Cell death and its relationship to viral infections: What are the ways to fight viruses?
International Journal for Innovation Education and Research
Cell death is a crucial process for maintaining homeostasis and the development of the organism. They are mainly characterized by apoptosis, necrosis and autophagy, being complex processes and essences for the immune system and balance of the human organism, especially when there are infectious agents such as viruses. Therefore, a bibliographic review was carried out seeking to deepen the knowledge of cell death applied to viruses, and its possible action against COVID-19, demonstrating the action and importance of understanding and understanding cell death pathways and applying their results as therapeutic targets. The results obtained showed the individual action of cell deaths against the virus in the immune system and emphasized the understanding of cell death pathways as fundamental for the development of drugs and therapies for viral control for already known viruses and for new viruses, such as Covid -19.
Inducible viral receptor, A possible concept to induce viral protection in primitive immune animals
Virology Journal, 2011
A pseudolysogen (PL) is derived from the lysogenic Vibrio harveyi (VH) which is infected with the VHS1 (Vibrio harveyi Siphoviridae-like 1) bacteriophage. The lysogenic Vibrio harveyi undergoes an unequivalent division of the extra-chromosomal VHS1 phage genome and its VH host chromosome and produces a true lysogen (TL) and pseudolysogen (PL). The PL is tolerant to super-infection of VHS1, as is of the true lysogen (TL), but the PL does not contain the VHS1 phage genome while the TL does. However, the PL can become susceptible to VHS1 phage infection if the physiological state of the PL is changed. It is postulated that this is due to a phage receptor molecule which can be inducible to an on-and-off regulation influence by an alternating condition of the bacterial host cell. This characteristic of the PL leads to speculate that this phenomenon can also occur in high organisms with low immunity such as shrimp. This article proposes a hypothesis that the viral receptor molecule on the target cell can play a crucial role in which the invertebrate aquaculture animals can become tolerant to viral infection. A possible mechanism may be that the target cell disrupts the viral receptor molecule to prevent super infection. This concept can explain a mechanism for the prevention of viral infection in invertebrate animals which do not have acquired immunity in response to pathogens. It can guide us to develop a mechanism of immunity to viral infection in low-evolved-immune animals. Also, it can be an additional mechanism that exists in high immune organism, as in human for the prevention of viral infection
Viral subversion of the immune system
Annual Review of …, 2000
Given their short generation times, a proper host defense against viral pathogens is essential and is aimed at several levels. Mechanical protection afforded by skin and epithelia can keep out many intruders, but viruses often possess specialized mechanisms to breach ...
The evolution of virus-induced apoptosis
Proceedings of the Royal Society B: Biological Sciences, 1997
Viruses from several di¡erent families are able to exploit their host's cell death programmes so as to maximize viral ¢tness. Consideration of the evolution of such strategies has lead to the suggestion that the virus should inhibit apoptosis, in order to prolong the life of the cell and thereby maximize the number of progeny virions. The host, on the other hand, should stimulate apoptosis thereby inhibiting viral growth and blocking viral spread. For example, the function of the latent membrane protein 1 (LMP1) of the Epstein^Barr virus and the bcl-2 homologue gene A179L of African swine fever virus is to inhibit apoptosis. However, in other cases it is the virus that stimulates cell death or the host that bene¢ts from inhibiting apoptosis, such as in fatal alphavirus encephalitis. This has been explained by assuming that virusinduced apoptosis in non-regenerating cells would be detrimental to the host. We present a mathematical framework for understanding virus-induced apoptosis which accounts for these two opposite solutions to virus infection with respect to the mode of virus replication and the life cycle of the target cell.
Viral modulation of cell death by inhibition of caspases
Archivum immunologiae et therapiae experimentalis, 2003
Caspases are key effectors of the apoptotic process. Some of them play important roles in the immune system, being involved in the proteolytic maturation of the key cytokines, including interleukin 1beta (IL-1beta) and IL-18. The latter directs the production of interferon gamma (IFN-gamma). Among pathogens, particularly viruses express various modulators of caspases that inhibit their activity by direct binding. By evading the apoptotic process, viruses can better control their production in the infected cell and avoid the attack of the immune system. Targeting the maturation of the key cytokines involved in the initiation of (antiviral) immune response helps to avoid recognition and eradication by the immune system. The three main classes of caspase inhibitors frequently found among viruses include serine proteinase inhibitors (serpins: CrmA/SPI-2), viral IAPs (vIAPs) and p35. Their molecular mechanisms of action, structures and overall influence on cellular physiology are discuss...
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Contribution of rip3 and mlkl to immunogenic cell death signaling in cancer chemotherapy
OncoImmunology, 2016
Chemotherapy can reinstate anticancer immunosurveillance through inducing tumor immunogenic cell death (ICD). Here, we show that anthracyclines and oxaliplatin can trigger necroptosis in murine cancer cell lines expressing receptor-interacting serine-threonine kinase 3 (RIP3) and mixed lineage kinase domain-like (MLKL). Necroptotic cells featured biochemical hallmarks of ICD and stimulated anticancer immune responses in vivo. Chemotherapy normally killed Rip3 ¡/¡ and Mlkl ¡/¡ tumor cells and normally induced caspase-3 activation in such cells, yet was unable to reduce their growth in vivo. RIP3 or MLKL deficiency abolished the capacity of dying cancer cells to elicit an immune response. This could be attributed to reduced release of ATP and high mobility group box 1 (HMGB1) by RIP3 and MLKL-deficient cells. Measures designed to compensate for deficient ATP and HMGB1 signaling restored the chemotherapeutic response of Rip3 ¡/¡ and Mlkl ¡/¡ cancers. Altogether, these results suggest that RIP3 and MLKL can contribute to ICD signaling and tumor immunogenicity.
Subverting Host Cell P21-Activated Kinase: A Case of Convergent Evolution across Pathogens
Pathogens (Basel, Switzerland), 2017
Intracellular pathogens have evolved a wide range of strategies to not only escape from the immune systems of their hosts, but also to directly exploit a variety of host factors to facilitate the infection process. One such strategy is to subvert host cell signalling pathways to the advantage of the pathogen. Recent research has highlighted that the human serine/threonine kinase PAK, or p21-activated kinase, is a central component of host-pathogen interactions in many infection systems involving viruses, bacteria, and eukaryotic pathogens. PAK paralogues are found in most mammalian tissues, where they play vital roles in a wide range of functions. The role of PAKs in cell proliferation and survival, and their involvement in a number of cancers, is of great interest in the context of drug discovery. In this review we discuss the latest insights into the surprisingly central role human PAK1 plays for the infection by such different infectious disease agents as viruses, bacteria, and p...
Current Approaches for Combination Therapy of Cancer: The Role of Immunogenic Cell Death
Cancers
Cell death resistance is a key feature of tumor cells. One of the main anticancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD). It has been suggested that ICD inducers are two different types according to their various activities. Here, we review the well-characterized DAMPs and focus on the different types of ICD inducers and recent combination therapies that can augment the immunogenicity of cancer cells.
Frontiers in Cellular and Infection Microbiology
The biology of the viral life cycle essentially includes two structural and functional entities—the viral genome and protein machinery constituting the viral arsenal and an array of host cellular components which the virus closely associates with—to ensure successful perpetuation. The obligatory requirements of the virus to selectively evade specific host cellular factors while exploiting certain others have been immensely important to provide the platform for designing host-directed antiviral therapeutics. Although the spectrum of host-virus interaction is multifaceted, host factors that particularly influence viral replication have immense therapeutic importance. During lytic proliferation, viruses usually form replication factories which are specialized subcellular structures made up of viral proteins and replicating nucleic acids. These viral niches remain distinct from the rest of the cellular milieu, but they effectively allow spatial proximity to selective host determinants. ...
Chronic intestinal inflammation in mice expressing viral Flip in epithelial cells
Mucosal immunology, 2018
Viruses are present in the intestinal microflora and are currently discussed as a potential causative mechanism for the development of inflammatory bowel disease. A number of viruses, such as Human Herpesvirus-8, express homologs to cellular FLIPs, which are major contributors for the regulation of epithelial cell death. In this study we analyzed the consequences of constitutive expression of HHV8-viral FLIP in intestinal epithelial cells (IECs) in mice. Surprisingly, expression of vFlip disrupts tissue homeostasis and induces severe intestinal inflammation. Moreover vFlip mice showed reduced Paneth cell numbers, associated with excessive necrotic cell death. On a molecular level vFlip expression altered classical and alternative NFκB activation. Blocking of alternative NFκB signaling by deletion of Ikka in vivo largely protected mice from inflammation and Paneth cell loss induced by vFLIP. Collectively, our data provide functional evidence that expression of a single viral protein ...
Cell Death & Disease, 2020
Oncolytic viruses have the potential to induce immunogenic cell death (ICD) that may provoke potent and long-lasting anti-cancer immunity. Here we aimed to characterize the ICD-inducing ability of wild-type Adenovirus (Ad), Semliki Forest virus (SFV) and Vaccinia virus (VV). We did so by investigating the cell death and immune-activating properties of virus-killed tumor cells. Ad-infection of tumor cells primarily activates autophagy, but also activate events of necroptotic and pyroptotic cell death. SFV infection on the other hand primarily activates immunogenic apoptosis while VV activates necroptosis. All viruses mediated lysis of tumor cells leading to the release of danger-associated molecular patterns, triggering of phagocytosis and maturation of dendritic cells (DCs). However, only SFV-infected tumor cells triggered significant T helper type 1 (Th1)-cytokine release by DCs and induced antigen-specific T-cell activation. Our results elucidate cell death processes activated upo...
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To kill or be killed: viral evasion of apoptosis
Nature Immunology, 2002
In the struggle between virus and host, control over the cell's death machinery is crucial for survival. Viruses are obligatory intracellular parasites and, as such, must modulate apoptotic pathways to control the lifespan of their host in order to complete their replication cycle. Many of the counter-assaults mounted by the immune system incorporate activation of the apoptotic pathway-particularly by members of the tumor necrosis factor cytokine family-as a mechanism to restrict viral replication.Thus, apoptosis serves as a powerful selective pressure for the virus to evade. However, for the host, success is harsh and potentially costly, as apoptosis often contributes to pathogenesis. Here we examine some of the molecular mechanisms by which viruses manipulate the apoptotic machinery to their advantage and how we (as vertebrates) have evolved and learned to cope with viral evasion.
Viral immune evasion: a masterpiece of evolution
Immunogenetics, 2002
Coexistence of viruses and their hosts imposes an evolutionary pressure on both the virus and the host immune system. On the one hand, the host has developed an immune system able to attack viruses and virally infected cells, whereas on the other hand, viruses have developed an array of immune evasion mechanisms to escape killing by the host's immune system. Generally, the larger the viral genome, the more diverse mechanisms are utilized to extend the time-window for viral replication and spreading of virus particles. In addition, herpesviruses have the capacity to hide from the immune system by their ability to establish latency. The strategies of immune evasion are directed towards three divisions of the immune system, i.e., the humoral immune response, the cellular immune response and immune effector functions. Members of the herpesvirus family are capable of interfering with the host's immune system at almost every level of immune clearance. Antibody recognition of viral epitopes, presentation of viral peptides by major histocompatibility complex (MHC) class I and class II molecules, the recruitment of immune effector cells, complement activation, and apoptosis can all be impaired by herpesviruses. This review aims at summarizing the current knowledge of viral evasion mechanisms.
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