HSV-1 Enhances the Energy Metabolism of Human Umbilical Cord Mesenchymal Stem Cells to Promote Virus Infection

Abstract

Aim: To explore the underlying influence of HSV type-1 (HSV-1) infection on the energy metabolism of human umbilical cord-derived mesenchymal stem cells (UCMSCs). Methods: UCMSCs (derived from different donors) were isolated from umbilical cord tissue, cultured and infected with HSV-1. Various virology and biochemical assays were used to assess cell viability and function, such as plaque formation assay and mitochondrial mass assay. Results: HSV-1 infection sharply activated mitochondrial biogenesis, increased glucose consumption, oxidative phosphorylation and glycolysis of UCMSCs. Treatment with rotenone (a metabolism antagonist) and iodoacetic acid significantly blocked the proliferation of HSV-1 in UCMSCs. Conclusion: This study demonstrates, for the first time, that HSV-1 infection affects the energy metabolism process of UCMSCs. Treatment with the appropriate metabolism antagonists might improve the safety and efficacy of clinical stem cell therapies.

Carnosic Acid Inhibits Herpes Simplex Virus Replication by Suppressing Cellular ATP Synthesis

“…The HSV-1 protein UL-16 also targets mitochondria and increases oxidative phosphorylation and ATP generation [34]. Moreover, inhibition of terminal oxidation was shown to inhibit HSV-1 replication in human umbilical cord-derived mesenchymal stem cells [35].…”

Interplay between cellular metabolism and DNA viruses

“…Studies showed that HSV increases OXPHOS, glucose consumption, and lactate production. These enhancements occur through elevating glucose uptake, and upregulation of PFKM (PFK‐1) activity, as well as PGC‐1α, NDUFB‐3, and CYC‐1 genes 111,112 . The activation of the glycolysis pathway can produce more pyruvate into mitochondria and increase OXPHOS, generating ATP 113 .…”

“…These enhancements occur through elevating glucose uptake, and upregulation of PFKM (PFK-1) activity, as well as PGC-1α, NDUFB-3, and CYC-1 genes. 111,112 The activation of the glycolysis pathway can produce more pyruvate into mitochondria and increase OXPHOS, generating ATP. 113 HSV-1 infection leads to elevated levels of PEP.…”