Towards SARS-COV-2 Effects on the Genetic Apparatus of Target Cells
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.
December 13, 2022; Published: January 05, 2023
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
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