Impact of SARS-CoV-2 variants on genome integrity and their involvement in inflammation

SARS-CoV-2 is an enveloped RNA virus with a genome of approximately 30,000 nucleotides.
From the ancestral form of the virus to the Omicron (Pango Lineage BA.1) variant, SARS-CoV-2
has accumulated a multitude of mutations and amino acid changes. Some of these have resulted in
changes in pathogenicity and in transmissibility. Since its appearance in late 2021, all circulating
genotypes have been sublineages of the Omicron variant, with the results of conserving, and even enriching, the
mutation profile of the virus.
Ancestral variants of SARS-Cov-2 have been observed to compromise genome integrity by causing
virus-induced DNA damage (VIDD) and by impeding DNA repair mechanisms. The effects
culminate in the activation of proinflammatory pathways and virus-induced senescence (VIS).
Three viral proteins (Orf6, NSP13, and N) play a significant role in these mechanisms. Specifically,
Orf6 and NSP13 promote the degradation of the DNA damage-response kinase, while the SARSCoV-2 N protein, by competing with 53BP1, leads to reduced DNA repair.
The objective of this study is investigate the impact of the Omicron mutations on VIDD, and to
better elucidate the role of the viral proteins in generating an inflammatory state by interfering with
the DNA damage repair mechanism.