Empty SV40 capsids increase survival of septic rats by eliciting numerous host signaling networks

February 12, 2020

The cover for issue 6 of Oncotarget features Figure 3, "The effect of NCs treatments on routine lab results during disease and recovery progress," by Ben-Nun-Shaul, et al.

Numerous previous attempts to develop therapeutic treatments, directed at discreet targets of the sepsis cascade, could not cope with the complex pathophysiology of sepsis and failed.

Studies in a severe rat sepsis model showed that pre-treatment by NCs led to a dramatic increase in survival, from zero to 75%.

Further studies are needed to determine whether when applied after sepsis onset, the NCs still improve outcomes.

Dr. Arieh Eden from the Department of Anesthesiology, Critical Care and Pain Medicine at the Lady Davis Carmel Medical Center in Haifa, Israel said in their Oncotarget Research Paper, "Sepsis affects millions of individuals annually worldwide, with a mortality of >25%" and according to the Cancer | Sepsis Alliance "Having cancer and undergoing certain treatments for cancer, such as chemotherapy, can result in a weakened immune system, putting you at higher risk for developing an infection that could lead to sepsis. Sometimes incorrectly called blood poisoning, sepsis is the body's often deadly response to infection." https://www.sepsis.org/sepsisand/cancer/

"Having cancer and undergoing certain treatments for cancer, such as chemotherapy, can result in a weakened immune system, putting you at higher risk for developing an infection that could lead to sepsis. Sometimes incorrectly called blood poisoning, sepsis is the body's often deadly response to infection."


It accounts for more than 50% of hospital deaths, with mortality rates of 10 20% for sepsis, 20 40% for severe sepsis, and 40 80% for septic shock.

In the present study the authors tested the hypothesis, based on their earlier unpublished research, that empty SV40 capsids would improve the outcome of sepsis.

Twenty years ago we established a procedure for the production of empty SV40 capsid, in order to develop a safe gene delivery vector, to be assembled in vitro from empty capsids and plasmid DNA of choice.

The underlying mechanism was up-regulation of Hsp/c70 and induction of the PI3K/Akt survival pathway, both seen exclusively in kidney tissue of NCs treated mice.

That study revealed that SV40 and/or its NCs elicit concurrently opposing pathways: cellular stress response, pro-apoptotic host defense, and Akt-1 survival pathway.

The Eden Research Team concluded in their Oncotarget paper, that these findings, and the dynamic adjustment of the therapeutic pathways to the recovery course, lead them to suggest that the effect of the NCs is tailored both to the type and to the temporal course of the injury, implying a general homeostatic activity.

The homeostatic nature of the NC activity is also manifested in their negligible effect on the normal control rats.
Full text - https://doi.org/10.18632/oncotarget.27448

Correspondence to - Ariella Oppenheim - ariellao@mail.huji.ac.il and Arieh Eden - ganyneden@gmail.com

Keywords - sepsis, empty SV40 capsids, RNAseq, signaling, cellular functions

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