Cell death and its relationship to viral infections: What are the ways to fight viruses? (original) (raw)
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20 Years of Cell Death - Chapter15.pdf
The ability of hosts to trigger cell death upon virus infection, especially apoptosis, is key in limiting the extent of viral propagation and damage to the organism. Many viruses through their own proteins have evolved around this hurdle by adapting their life cycles around the process of cell death where some viruses reproduce favorably when the infected cells are killed. It is generally accepted that most human viruses play with the cell death pathways, depending on the cells infected. Common targets of virus-induced cell death (apoptosis mostly) are cells of the immune system, and this can even determine the outcome and severity of viral infection. Viruses that reproduce less in cells that activate cell death pathways have viral proteins that turn on stress response signaling like autophagy to prolong the life of their host as viruses are produced. We also have our disposal knowledge about individual viral proteins (and in some cases, specific domains) inducing or inhibiting cell death pathways (apoptosis, autophagy) in different cells. Induction or repression of various cell survival pathways, therefore, plays an important role in viral pathogenicity apart from the canonical stress pathways. A better understanding of the signaling pathways that viruses affect to kill or protect the infected cells will allow for the development of new antiviral therapies. This review focuses on key cell death and survival pathways manipulated during influenza, dengue and chikungunya infection, with special emphasis on the role of viral proteins, thus exploring the chance of using them for therapeutics.
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.
Cell Death and Its Different Modes: History of Understanding and Current Trends
International Journal of Biochemistry Research & Review, 2019
Discussions about what is life continue to struggle; there are pros and cons for whether a virus is alive. However, an opposite thing – cell death – appears to be tantamount important and equally not-easygoing to define. Nevertheless, our current knowledge about eukaryotic cell death has made a long way and resulted in a fruitful outcome: starting from three types of cell death (type I, II and III which are mainly applicable to eukaryotic cells of organisms from the biological kingdom animalia) in 1970s, Nomenclature Committee on Cell Death has named already twelve cell death forms in 2018, including the above mentioned apoptosis, autophagy and necrosis among them. How the scientific attitude towards cellular demise evolved and various aspects of different cell death modes are reviewed in this article.
Cell death in health and disease
Journal of Cellular and Molecular Medicine, 2007
Cell death is clearly an important factor in development, homeostasis, pathology and in aging, but medical efforts based on controlling cell death have not become major aspects of medicine. There are several reasons why hopes have been slow to be fulfilled, and they present indications for new directions in research. Most effort has focused on the machinery of cell death, or the proximate effectors of apoptosis and their closely associated and interacting proteins. But cells have many options other than apoptosis. These include autophagy, necrosis, atrophy and stepwise or other alternate means of self-disassembly. The response of a cell to a noxious or otherwise intimidating signal will depend heavily on the history, lineage and current status of the cell. Many metabolic and other processes adjust the sensitivity of cells to signals, and viruses aggressively attempt to regulate the death of their host cells. Another complicating factor is that many deathassociated proteins may have functions totally unrelated to their role in cell death, generating the possibility of undesirable side effects if one interferes with them. In the future, the challenge will be more to understand the challenge to the cell from a more global standpoint, including many more aspects of metabolism, and work toward alleviating or provoking the challenge in a targeted fashion.
Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets
Molecules
COVID-19 is the name of the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in 2019. The virus–host-specific interactions, molecular targets on host cell deaths, and the involved signaling are crucial issues, which become potential targets for treatment. Spike protein, angiotensin-converting enzyme 2 (ACE2), cathepsin L-cysteine peptidase, transmembrane protease serine 2 (TMPRSS2), nonstructural protein 1 (Nsp1), open reading frame 7a (ORF7a), viral main protease (3C-like protease (3CLpro) or Mpro), RNA dependent RNA polymerase (RdRp) (Nsp12), non-structural protein 13 (Nsp13) helicase, and papain-like proteinase (PLpro) are molecules associated with SARS-CoV infection and propagation. SARS-CoV-2 can induce host cell death via five kinds of regulated cell death, i.e., apoptosis, necroptosis, pyroptosis, autophagy, and PANoptosis. The mechanisms of these cell deaths are well established and can be disrupted by synthetic small...
Regulation of cell survival and death during Flavivirus infections
World journal of biological chemistry, 2014
Flaviviruses, ss(+) RNA viruses, include many of mankind's most important pathogens. Their pathogenicity derives from their ability to infect many types of cells including neurons, to replicate, and eventually to kill the cells. Flaviviruses can activate tumor necrosis factor α and both intrinsic (Bax-mediated) and extrinsic pathways to apoptosis. Thus they can use many approaches for activating these pathways. Infection can lead to necrosis if viral load is extremely high or to other types of cell death if routes to apoptosis are blocked. Dengue and Japanese Encephalitis Virus can also activate autophagy. In this case the autophagy temporarily spares the infected cell, allowing a longer period of reproduction for the virus, and the autophagy further protects the cell against other stresses such as those caused by reactive oxygen species. Several of the viral proteins have been shown to induce apoptosis or autophagy on their own, independent of the presence of other viral protei...
Future Virology, 2020
Human gastroenteritis viruses are amid the major causes of disease worldwide, responsible for more than 2 million deaths per year. Human noroviruses play a leading role in the gastroenteritis outbreaks and the continuous emergence of new strains contributes to the significant morbidity and mortality. Many aspects of the viral entry and infection process remain unclear, including the major response of the host cell to the virus, which is the trigger of several programmed cell death related mechanisms. In this review, we assessed apoptosis and autophagy at various stages in the infection process to provide better understanding of the viral–host interaction. This brings us closer to fully understanding how noroviruses work, thus allowing the development of specific antiviral therapies.