Analysis of pathways elicited by empty SV40 capsids (VLPs) in septic rats 24 hours post 2CLP operation

During the first hours after infection, before SV40 DNA enters the nucleus, empty capsids (VLPs) and the wild-type virus have the same effect on cellular signaling. VLPs were previously found to ameliorate toxic acute kidney injury (AKI) in a mouse model, counteracting apoptosis by inducing the Akt-1 survival pathway. Here we tested their effect on severe sepsis in rats. VLP pre-treatment increased survival and recovery from zero to 75%. RNAseq studies demonstrated that unlike AKI, here the VLPs did not induce survival pathways. Instead they affected thousands of genes and many cellular functions, eliminating deleterious pathways and inducing beneficial ones: immune response, resolution of inflammation, regeneration and cell and system homeostasis. In contrast, only four genes were affected following VLP administration to healthy rats. We propose that SV40 VLPs respond specifically to perturbation in cellular activities. The study suggests that diseases with complex pathophysiology may require treatments affecting wide-spectrum functions. Overall design: Sprague-Dawley rats were randomly divided into 4 groups, each containing 3 replicates: Control rats that received vehicle (saline) only (VO), a second control, rats that received VLPs only (VLPs), and two groups of 2CLP-insulted rats, one that received vehicle only (2CLP+VO) and the second received VLPs (2CLP+VLP). VLPs were injected through the tail-vein at a dose of 0.3 mg/kg, on 3 consecutive days (0.1 mg/kg daily) prior to the insult. Lungs were harvested 24 hours post the 2CLP insult.