Acta Scientific Microbiology (ISSN: 2581-3226)

Review Article Volume 6 Issue 2

Towards SARS-COV-2 Effects on the Genetic Apparatus of Target Cells

Zinaida Klestova*

Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany

*Corresponding Author: Zinaida Klestova, Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany.

Received: December 13, 2022; Published: January 05, 2023

Abstract

Integrity of a cellular genome is under constant attack from DNA-damaging agents. These include endogenous cellular compounds, as well as exogenous agents such as RNA viruses. The latter can cause significant DNA damage, even if viral replication occurs exclusively in the cytoplasm. The DNA damage response (DDR) comprises sensors, transducers and effectors, which together form a signaling cascade involving complex protein-protein interactions and post-translational modifications. Initiation of this cascade leads to cell cycle arrest and activation of DNA repair pathways. For example, the kinases ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK) are primarily activated by double-strand breaks (DSBs), whereas ataxia telangiectasia and Rad3-related (ATR) kinase is stimulated at regions of single-stranded DNA (ssDNA) that arise at DSBs or stalled replication forks.

This review summarizes known effects of SARS-CoV-2 and other coronaviruses on the genome integrity of infected cells and the induction of DNA damage responses. Notably, SARS-CoV-2 has been suggested to affect DNA integrity of both somatic and germ cells. One focus of this article will be on the formation of so-called “virus factories” near microtubules and their effects on cell division and chromosome segregation. Furthermore, the effect of co- or superinfections with other viruses (e.g., influenza, rhino-, entero-, noroviruses, etc.) and a potential exacerbation of DNA damage will be presented.

Elucidating the interactions of RNA viruses with host DNA damage responses and the induction of genomic instability will not only provide important insights into viral pathogenesis, but may also help to advance current therapeutic approaches.

Keywords: SARS-CoV-2; Target Cells; Genetic Instability; Chromosome Damage

References

  1. Aiello SE MMA. “MSD Veterinary Manual”. 11 edn. Merck and Co., Inc., Rahway, NJ, USA (2016).
  2. Antonin W and Neumann H. “Chromosome condensation and decondensation during mitosis”. Current Opinion in Cell Biology 40 (2016): 15-22.
  3. Bell JC and Straight AF. “Condensing chromosome condensation”. Nature Cell Biology 17 (2015): 964-965.
  4. Beyerstedt S., et al. “COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection”. European Journal of Clinical Microbiology and Infectious Diseases 40 (2021): 905-919.
  5. Bian L., et al. “MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment”. Molecular Cancer 18 (2019): 169.
  6. Boyer J., et al. “Adenovirus E4 34k and E4 11k inhibit double strand break repair and are physically associated with the cellular DNA-dependent protein kinase”. Virology 263 (1999): 307-312.
  7. Bridges JP., et al. “Respiratory epithelial cell responses to SARS-CoV-2 in COVID-19”. Thorax 77 (2022): 203-209.
  8. Cannan WJ and Pederson DS. “Mechanisms and Consequences of Double-Strand DNA Break Formation in Chromatin”. Journal of Cellular Physiology 231 (2016): 3-14.
  9. Cantell K., et al. “Virological studies on chromosome damage of HeLa cells induced by myxoviruses”. Annales Medicinae Experimentalis et Biologiae Fenniae 44 (1966): 255-259.
  10. Halaji M., et al. “Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19”. InfezMed 28 (2020): 6-17.
  11. Herceg Z and Hainaut P. “Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis”. Molecular Oncology 1 (2007): 26-41.
  12. Higgs MR., et al. “Liver let die': oxidative DNA damage and hepatotropic viruses”. Journal of General Virology 95 (2014): 991-1004.
  13. Huang C., et al. “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China”. Lancet 395 (2020): 497-506.
  14. Kirsch-Volders M and Fenech M. “Inflammatory cytokine storms severity may be fueled by interactions of micronuclei and RNA viruses such as COVID-19 virus SARS-CoV-2. A hypothesis”. M Mutation Research/Reviews in Mutation Research 788 (2021): 108395.
  15. Knyazev E., et al. “Endocytosis and Transcytosis of SARS-CoV-2 Across the Intestinal Epithelium and Other Tissue Barriers”. Frontiers in Immunology 12 (2021): 636966.
  16. Li FQ., et al. “Cell cycle arrest and apoptosis induced by the coronavirus infectious bronchitis virus in the absence of p53”. Virology 365 (2007): 435-445.
  17. Logue JK., et al. “Sequelae in Adults at 6 Months After COVID-19 Infection”. JAMA Network Open 4 (2021): e210830.
  18. Lukassen S., et al. “SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells”. EMBO Journal 39 (2020): e105114.
  19. Majumder K and Morales AJ. “Utilization of Host Cell Chromosome Conformation by Viral Pathogens: Knowing When to Hold and When to Fold”. Frontiers on Immunology 12 (2021): 633762.
  20. Malone B., et al. “Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design”. Nature Reviews Molecular Cell Biology 23 (2022): 21-39.
  21. Manna S., et al. “Molecular pathogenesis of secondary bacterial infection associated to viral infections including SARS-CoV-2”. Journal of Infection and Public Health 13 (2020): 1397-1404.
  22. Mehta A and Haber JE. “Sources of DNA double-strand breaks and models of recombinational DNA repair”. Cold Spring Harbor Perspectives in Biology 6 (2014): a016428.
  23. Memish ZA., et al. “Middle East respiratory syndrome”. Lancet 395 (2020): 1063-1077.
  24. Ming X., et al. “Porcine Enteric Coronavirus PEDV Induces the ROS-ATM and Caspase7-CAD-gammaH2AX Signaling Pathways to Foster Its Replication”. Viruses 14 (2022).
  25. Netherton CL and Wileman T. “Virus factories, double membrane vesicles and viroplasm generated in animal cells”. Current Opinion in Virology 1 (2011): 381-387.
  26. Ntouros PA., et al. “Effective DNA damage response after acute but not chronic immune challenge: SARS-CoV-2 vaccine versus Systemic Lupus Erythematosus”. Clinical Immunology 229 (2021): 108765.
  27. O'Connor PM., et al. “Role of the cdc25C phosphatase in G2 arrest induced by nitrogen mustard”. Proceedings of the National Academy of Sciences of the United States of America 91 (1994): 9480-9484.
  28. Pizzato M., et al. “SARS-CoV-2 and the Host Cell: A Tale of Interactions”. Frontiers in Virology 1 (2022).
  29. Pizzorno ND MN., et al. “Chapter 14 - Cancer: Integrated naturopathic support”. 3d edn (2016).
  30. Reshi ML., et al. “RNA Viruses: ROS-Mediated Cell Death”. International Journal of Cell Biology (2014): 467452.
  31. Roos WP and Kaina B. “DNA damage-induced cell death by apoptosis”. Trends in Molecular Medicine 12 (2006): 440-450.
  32. Rosendahl Huber A., et al. “The Mutagenic Impact of Environmental Exposures in Human Cells and Cancer: Imprints Through Time”. Frontiers in Genetics 12 (2021): 760039.
  33. Ryan EL., et al. “Activation of the DNA Damage Response by RNA Viruses”. Biomolecules 6 (2016): 2.
  34. Santillan Martinez ., et al. “CRISPR/Cas9-targeted mutagenesis of the tomato susceptibility gene PMR4 for resistance against powdery mildew”. BMC Plant Biology 20 (2020): 284.
  35. Scialo F, ., et al. “ACE2: The Major Cell Entry Receptor for SARS-CoV-2”. Lung 198 (2020): 867-877.
  36. Sepe S., et al. “DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging”. EMBO Report 23 (2022): e53658.
  37. Spudich S and Nath A. “Nervous system consequences of COVID-19”. Science 375 (2022): 267-269.
  38. Stracker TH., et al. “The ATM signaling network in development and disease”. Frontiers in Genetics 4 (2013): 37.
  39. Sun Q., et al. “Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province”. Annals of Intensive Care 10 (2020): 33.
  40. Victor J., et al. “SARS-CoV-2 triggers DNA damage response in Vero E6 cells”. Biochemical and Biophysical Research Communications 579 (2021): 141-145.
  41. Vijaya Lakshmi AN., et al. “Detection of influenza virus induced DNA damage by comet assay”. Mutation Research 442 (1999): 53-58.
  42. Vilenchik MM and Knudson AG. “Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer”. Proceedings of the National Academy of Sciences of the United States of America 100 (2003): 12871-12876.
  43. Xu L., et al. “The cellular RNA helicase DDX1 interacts with coronavirus nonstructural protein 14 and enhances viral replication”. Journal of Virology 84 (2010): 8571-8583.
  44. Xu LH., et al. “Coronavirus infection induces DNA replication stress partly through interaction of its nonstructural protein 13 with the p125 subunit of DNA polymerase delta”. Journal of Biological Chemistry 286 (2011): 39546-39559.
  45. Yazdi PT., et al. “SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint”. Genes Development 16 (2002): 571-582.
  46. You LR., et al. “Hepatitis C virus core protein enhances NF-kappaB signal pathway triggering by lymphotoxin-beta receptor ligand and tumor necrosis factor alpha”. Journal of Virology 73 (1999): 1672-1681.
  47. Zhang J., et al. “A systemic and molecular study of subcellular localization of SARS-CoV-2 proteins”. Signal Transduction and Targeted Therapy 5 (2020): 269.
  48. Zhang N., et al. “Generation and Molecular Characterization of CRISPR/Cas9-Induced Mutations in 63 Immunity-Associated Genes in Tomato Reveals Specificity and a Range of Gene Modifications”. Frontiers in Plant Science 11 (2020): 10.
  49. Вашкова ВВ ЛДК. “Влияние некоторых арбовирусов на митотическую активность и хромосомы клеток культуры ткани Цитология и генетика” 4 (1970): 300-303.
  50. Гордеева. “О механизме мутагенного действия вируса клещевого энцефалита”. ВОПРОСЫ ВИРУСОЛОГИИ 2 (1979): 76-79.

Citation

Citation: Zinaida Klestova. “Towards SARS-COV-2 Effects on the Genetic Apparatus of Target Cells". Acta Scientific Microbiology 6.2 (2023): 09-21.

Copyright

Copyright: © 2022 Zinaida Klestova. 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.




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