Cellular senescence as a source of SARS-CoV-2 quasispecies

Karakasiliotis, Ioannis; Lagopati, Nefeli; Evangelou, Konstantinos; Gorgoulis, Vassilis G

In depth analysis of SARS-CoV-2 biology and pathogenesis is rapidly unravelling the mechanisms through which the virus induces all aspects of COVID-19 pathology. Emergence of hundreds of variants and several important variants of concern has focused research on the mechanistic elucidation of virus mutagenesis. RNA viruses evolve quickly either through the error prone polymerase or the RNA-editing machinery of the cell. In this review we are discussing the links between cellular senescence, a natural aging process that has been recently linked to SARS-CoV-2 infection, and virus mutagenesis through the RNA-editing enzymes APOBEC. The action of APOBEC, enhanced by cellular senescence, is hypothesized to assist the emergence of novel variants, called quasispecies, within a cell or organism. These variants when introduced to the community may lead to the generation of a variant of concern, depending on fitness and transmissibility of the new genome. Such a mechanism of virus evolution may highlight the importance of inhibitors of cellular senescence during SARS-CoV-2 clinical treatment.