The viruses used in this article from BrainVTA are in the table below

Senescent cells, which arise due to damage-associated signals, are apoptosis-resistant and can express a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP). We recently reported that a component of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface protein, S1, can amplify the SASP of senescent cultured human cells and that a related mouse β-coronavirus, mouse hepatitis virus (MHV), increases SASP factors and senescent cell burden in infected mice. Here, we show that SARS-CoV-2 induces senescence in human non-senescent cells and exacerbates the SASP in human senescent cells through Toll-like receptor-3 (TLR-3). TLR-3, which senses viral RNA, was increased in human senescent compared to non-senescent cells.  Notably, genetically or pharmacologically inhibiting TLR-3 prevented senescence induction and SASP amplification by SARS-CoV-2 or Spike pseudotyped virus. While an artificial TLR-3 agonist alone was not sufficient to induce senescence, it amplified the SASP in senescent human cells. Consistent with these findings, lung p16INK4a+ senescent cell burden was higher in patients who died from acute SARS-CoV-2 infection than other causes. Our results suggest that induction of cellular senescence and SASP amplification through TLR-3 contribute to SARS-CoV-2 morbidity, indicating that clinical trials of senolytics and/or SASP/TLR-3 inhibitors for alleviating acute and long-term SARS-CoV-2 sequelae are warranted.

Figure 1. Toll-like receptor-3 (TLR-3) is increased in senescent vs. non-senescent human kidney endothelial cells and preadipocytes.

In this study, the authors examined innate immune responses to SAR-CoV-2 and links to cellular senescence. They found that both a Spike pseudotyped virus (pseudovirus) and the genuine SARS-CoV-2 virus can induce senescence in human cells. Furthermore, the senescent cell SASP was amplified by TLR-3-dependent signaling. Clinical trials appear be warranted to ascertain if senolytics, agents that selectively eliminate senescent cells, senomorphics, which inhibit the SASP, and/or TLR-3 inhibitors can alleviate acute or long-term sequelae of SARS-CoV-2 infection.
 

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