Acta Scientific Microbiology (ISSN: 2581-3226)

Review ArticleVolume 4 Issue 6

Generate Intracellular Oxidative Stress is an Obligatory Mechanism of RNA Viruses During the Infectious Process

Carlos A Guerrero*

Department of Physiological Sciences, Faculty of Medicine, Universidad Nacional de Colombia, Bogota, Capital District, Colombia

*Corresponding Author: Carlos A Guerrero, Department of Physiological Sciences, Faculty of Medicine, Universidad Nacional de Colombia, Bogota, Capital District, Colombia.

Received: April 09, 2021; Published: May 17, 2021

Citation: Carlos A Guerrero. “Generate Intracellular Oxidative Stress is an Obligatory Mechanism of RNA Viruses During the Infectious Process”. Acta Scientific Microbiology 4.6 (2021): 70-81.

  Viruses, upon contact with the host cell, make conformational changes in their capsid proteins, leading to the emergence of molecular domains needed for binding to cell receptors in order to facilitate penetration of the virus into the cell. Generally, these conformational changes require the participation of molecules with redox capacity in the cell membrane. Once viruses enter, they need to induce conditions of cellular stress, usually oxidative stress, rapidly. This is a necessary condition for the cell to express molecular factors necessary for the viral RNA to be translated into the corresponding proteins that will allow a successful viral infection. In parallel, or as a consequence of the same oxidative process, the virus induces pro-inflammatory pathways such as NF-kB and concomitantly inhibits anti-inflammatory pathways as superoxide dismutase, Nrf2, and PPARγ. Likewise, the viral infection maintains the oxidative condition because it allows the assembly of virions by facilitating the native conformation of their proteins in which the formation of intermolecular disulfide bridges occurs. Under these conditions, the administration of drugs or antioxidant molecules interferes with the virus's oxidative conditions for its entry, replication, and assembly of new virions. In this way, the amount of virions generated per infected cell is drastically reduced, giving the immune system the opportunity to control the infection or reduce its aggressiveness.

Keywords: IRES; NF-κB; ROS; Oxidative Stress; Antioxidants

Bibliography

  1. Zhang Z., et al. "Flaviviridae viruses and oxidative stress: implications for viral pathogenesis". Oxidative Medicine and Cellular Longevity (2019): 2019.
  2. Camini FC., et al. "Implications of oxidative stress on viral pathogenesis". Archives of Virology 162 (2017): 907-917.
  3. Delgado-Roche L., et al. “Oxidative stress as key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection”. Archives of Medical Research 5 (2020): 384-387.
  4. Suhail S., et al. "Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A Review". Protein Journal6 (2020): 644-656.
  5. Guerrero CA., et al. "Inflammatory and oxidative stress in rotavirus infection". World Journal of Virology 5 (2016): 38.
  6. Khomich OA., et al. "Redox biology of respiratory viral infections". Viruses 10 (2018): 392.
  7. Struzik J., et al. "Manipulation of non-canonical NF-κB signaling by non-oncogenic viruses". Archivum Immunologiae et Therapiae Experimentalis 67 (2019): 41-48.
  8. Gómez D., et al. "PPARγ agonists as an anti-inflammatory treatment inhibiting rotavirus infection of small intestinal villi". PPAR Research Open Access 2016 (2016).
  9. Guerrero CA., et al. "Inhibition of rotavirus infection in cultured cells by N-acetyl-cysteine, PPARγ agonists and NSAIDs". Antiviral Research 96 (2012): 1-12.
  10. Guerrero CA., et al. "Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine, peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2 inhibitors". Memórias do Instituto Oswaldo Cruz 108 (2013): 741-754.
  11. Guerrero CA., et al. "N‐Acetylcysteine Treatment of Rotavirus‐Associated Diarrhea in Children". Pharmacotherapy 34 (2014): e333-e340.
  12. Yang Y., et al. "IRES-mediated cap-independent translation, a path leading to hidden proteome". Journal of Molecular Cell Biology 11 (2019): 911-919.
  13. Godet AC., et al. "IRES trans-acting factors, key actors of the stress response". International Journal of Molecular Sciences 20 (2019): 924.
  14. Koch A., et al. "Quantifying the dynamics of IRES and cap translation with single-molecule resolution in live cells". Nature Structural and Molecular Biology 27 (2020): 1095-1104.
  15. Kwan T., et al. "Noncanonical translation initiation in eukaryotes". Cold Spring Harbor Perspectives in Biology 11 (2019): a032672.
  16. Yang D., et al. "The identification of an internal ribosomal entry site in the 5′-untranslated region of p53 mRNA provides a novel mechanism for the regulation of its translation following DNA damage". Oncogene 25 (2006): 4613-4619.
  17. Lee C., et al. "Therapeutic modulation of virus-induced oxidative stress via the Nrf2-dependent antioxidative pathway". Oxidative Medicine and Cellular Longevity 2018 (2018): 6208067
  18. Miao Z., et al. "Secondary structure of the SARS-CoV-2 5’-UTR". RNA Biology (2020): 1-10.
  19. Lapointe CP., et al. "Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome inhibits translation initiation". Proceedings of the National Academy of Sciences of the United States of America 6 (2021): e2017715118.
  20. Griffiths A., et al. "An unusual internal ribosome entry site in the herpes simplex virus thymidine kinase gene". Proceedings of the National Academy of Sciences of the United States of America 102 (2005): 9667-9672.
  21. Cecchini R. "SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression". Medical Hypotheses 143 (2020): 110102.
  22. Banerjee AK., et al. "SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses". Cell 183 (2020): 1325-1339.
  23. Mehta P., et al. "Collaboration, COVID-19: consider cytokine storm syndromes and immunosuppression". Lancet 395 (2020): 1033.
  24. Chen Y., et al. "Mitochondria, oxidative stress and innate immunity". Frontiers in Physiology 9 (2018): 1487.
  25. Poe FL. "N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2". Medical Hypotheses (2020): 109862.
  26. Geiler J., et al. "N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus". Biochemical Pharmacology 79 (2010): 413-420.
  27. Huang S., et al. "PPAR-γ in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection". Journal of Virology9 (2019): e00030-19.
  28. Gopal R., et al. "Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection". Viruses 11 (2019): 505.
  29. Ciavarella C., et al. "Pasquinelli, Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease". Molecules 25 (2020): 2076.
  30. Liu Y., et al. "Experience of N-acetylcysteine airway management in the successful treatment of one case of critical condition with COVID-19". Medicine (Baltimore)42 (2020): e22577.
  31. Sreekanth GP., et al. "Drug repurposing of N-acetyl cysteine as antiviral against dengue virus infection". Antiviral Research 166 (2019): 42-55.
  32. Singh J., et al. "SARS-CoV2 infectivity is potentially modulated by host redox status". Computational and Structural Biotechnology Journal 18 (2020): 3705-3711.
  33. Guthappa R. "Molecular Docking Studies of N-Acetyl Cysteine, Zinc Acetyl Cysteine and Niclosamide on SARS Cov 2 Protease and Its Comparison with Hydroxychloroquine". (2020).
  34. Nasi A., et al. "Reactive oxygen species as an initiator of toxic innate immune responses in retort to SARS-CoV-2 in an ageing population, consider N-acetylcysteine as early therapeutic intervention" Toxicology Reports 7 (2020): 768-771.
  35. Huang J., et al. "SARS-CoV-2 infection of pluripotent stem cell-derived human lung alveolar type 2 cells elicits a rapid epithelial-intrinsic inflammatory response". Cell Stem Cell 6 (2020): 962-973.e7.
  36. Kim JH., et al. "Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)‐κB and NF‐κB‐regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis". Molecular Nutrition and Food Research 56 (2012): 454-465.
  37. Bellavite P., et al. "Hesperidin and SARS-CoV-2: New Light on the Healthy Function of Citrus Fruits". Antioxidants (Basel)8 (2020): 742.
  38. Bai Z., et al. "EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells". Gut Pathogens 12 (2020): 1-12.
  39. Checconi P., et al. "Redox-Modulating Agents in the Treatment of Viral Infections". International Journal of Molecular Sciences 21 (2020): 4084.
  40. Patra U., et al. "Progressive Rotavirus Infection Downregulates Redox-Sensitive Transcription Factor Nrf2 and Nrf2-Driven Transcription Units". Oxidative Medicine and Cellular Longevity 2020 (2020).
  41. Horowitz RI., et al. "Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases". Respiratory Medicine Case Reports (2020): 101063.
  42. Wang Y., et al. "N-Acetyl cysteine effectively alleviates Coxsackievirus B-Induced myocarditis through suppressing viral replication and inflammatory response". Antiviral Research 179 (2020): 104699.
  43. Shi Z., et al. "N-Acetylcysteine to Combat COVID-19: An Evidence Review". Therapeutics and Clinical Risk Management 16 (2020): 1047.
  44. Jorge-Aarón RM., et al. "N-acetylcysteine as a potential treatment for COVID-19". Future Microbiology (2020): 959-962.
  45. Ibrahim H., et al. "Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine". Clinical Immunology 219 (2020): 108544.
  46. Codo AC., et al. "Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1α/glycolysis dependent axis". Cell Metabolism 32 (3) (2020): 437-446.e5.
  47. Calderon MN., et al. " Inhibiting rotavirus infection by membrane-impermeant thiol/disulfide exchange blockers and antibodies against protein disulfide isomerase". Intervirology 55 (2012): 451-464.
  48. Rivera M., et al. "Thiol/disulfide exchange occurs in rotavirus structural proteins during contact with intestinal villus cell surface". Acta Virology 64 (2020): 44-58.
  49. Bhattacharyay S., et al. "Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor". ACS Omega26 (2020): 16292-16298.
  50. De Flora S., et al. "Rationale for the use of N‐acetylcysteine in both prevention and adjuvant therapy of COVID‐19". FASEB Journal 34 (2020): 13185-13193.
  51. Reshi ML., et al. "RNA viruses: ROS-mediated cell death". International Journal of Cell Biology 2014 (2014): 467452.
  52. Hendrickson R.G. "What is the most appropriate dose of N-acetylcysteine after massive acetaminophen overdose?". Clinical Toxicology 57 (2019): 686-691.

Copyright: © 2021 Carlos A Guerrero. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



News and Events


  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for Upcoming Issue
    The last date for submission of articles for regular Issues is June 25, 2021.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of “Best Article of the Issue”.
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.
  • Contact US