Vesicular Stomatitis Virus Induces NF-κB-Dependent Senescence to Mediate Persistent Inflammation and Injury.

Abstract

Cell senescence, induced by various internal and external stresses, plays a significant role in the development of various diseases such as cancer, neurodegeneration, and infections. Viral infections can also induce cellular senescence, known as virus-induced senescence (VIS), which occurs in close correlation with the severity of the viral infections. However, due to the unclear mechanisms underlying VIS, the effective inhibition of VIS during viral infections is challenging, leading to rapid disease progression. This study utilized the widely used vesicular stomatitis virus (VSV) model virus to simulate RNA virus infections for exploring the mechanisms by which RNA viruses induce cellular senescence. The results indicated that VSV infection, both in vitro and in vivo, could significantly induce the upregulation of senescence-associated markers and the secretion of the senescence-associated secretory phenotype (SASP), promoting the senescence process. Further research found that the activation of the NF-κB pathway played a crucial role in VSV-induced cellular senescence. Targeted inhibition of the NF-κB pathway could reduce the level of organ senescence induced by viral infections, decrease the expression of SASP inflammatory factors, and ameliorate tissue damage in mice. Overall, our findings reveal the mechanisms underlying RNA virus-associated VIS and provide potential targets for inhibiting the occurrence of VIS and preventing disease progression.