Empty SV40 capsids increase survival of septic rats by eliciting numerous host signaling networks that participate in a number of systemic functions

Orly Ben-Nun-Shaul, Rohit Srivastava, Sharona Elgavish, Shashi Gandhi, Yuval Nevo, Hadar Benyamini, Arieh Eden*, Ariella Oppenheim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Sepsis is an excessive, dysregulated immune response to infection that activates inflammatory and coagulation cascades, which may lead to tissue injury, multiple organ dysfunction syndrome and death. Millions of individuals die annually of sepsis. To date, the only treatment available is antibiotics, drainage of the infection source when possible, and organ support in intensive care units. 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. Here we describe a novel treatment, based on empty capsids of SV40 (nanocapsids - NCs). Studies in a severe rat sepsis model showed that pre-treatment by NCs led to a dramatic increase in survival, from zero to 75%. Transcript analyses (RNAseq) demonstrated that the NC treatment is a paradigm shift. The NCs affect multiple facets of biological functions. The affected genes are modified with time, adjusting to the recovery processes. The NCs effect on normal control rats was negligible. The study shows that the NCs are capable of coping with diseases with intricate pathophysiology. Further studies are needed to determine whether when applied after sepsis onset, the NCs still improve outcome.

Original languageAmerican English
Pages (from-to)574-588
Number of pages15
JournalOncotarget
Volume11
Issue number6
StatePublished - 11 Feb 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 Impact Journals LLC. All rights reserved.

Keywords

  • Cellular functions
  • Empty SV40 capsids
  • RNAseq
  • Sepsis
  • Signaling

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