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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.

UVA irradiation stimulates the production of reactive oxygen species (ROS), which results in oxidative stress, cellular damage, and ultimately, cell death by interacting with other intracellular molecules. In the present study, we explored the protective role of Dihydromyricetin (DHM,1.25-10μM) against UVA-induced inflammation response and apoptosis in the human keratinocyte cell line (HaCaT cells) and the underlying mechanisms. DHM pre-treatment significantly increased HaCaT cell viability and suppressed UVA-induced production of inflammatory cytokines, as well as apoptosis of HaCaT cells. Moreover, DHM pre-treatment prohibited UVA-induced ROS generation, mitochondrial membrane potential decrease, and the phosphorylation of histone H2AX(γ-H2AX), a sensitive biomarker for DNA damage. Meanwhile, DHM could enhance GSH-Px activity and decrease the content of MDA in UVA ray treated HaCaT cells. Notably, the anti-apoptotic potential of DHM was correlated with an increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-xl) and decreased expression of pro-apoptotic proteins (Bax), as well as the inhibition of caspase proteins activation. Additionally, DHM treatment also prevented the nuclear translocation of NF-κB/p65 and the phosphorylation of c-Jun. N-terminal kinase (JNK), which is an upstream modulator of NF-κB/p65. Therefore, DHM may be potentially useful in the prevention of UVA-induced skin damage.

Herpes simplex virus type 1 (HSV-1), a member of the herpesviridae, causes a variety of human viral diseases globally. Although a series of antiviral drugs are available for the treatment of infection and suppression of dissemination, HSV-1 remains highly prevalent worldwide. Therefore, the development of novel antiviral agents with different mechanisms of action is a matter of extreme urgency. During the proliferation of HSV-1, capsid assembly is essential for viral growth, and it is highly conserved in all HSV-1 strains. In this study, small interfering RNAs (siRNAs) against the HSV-1 capsid protein were screened to explore the influence of silencing capsid expression on the replication of HSV-1. We designed and chemically synthesized siRNAs for the capsid gene and assessed their inhibitory effects on the expression of target mRNA and the total intracellular viral genome loads by quantitative real-time PCR, as well as on the replication of HSV-1 via plaque reduction assays and electron microscopy. Our results showed that siRNA was an effective approach to inhibit the expression of capsid protein encoding genes including UL18, UL19, UL26, UL26.5, UL35 and UL38 in vitro. Interference of capsid proteins VP23 (UL18) and VP5 (UL19) individually or jointly greatly affected the replication of clinically isolated acyclovir-resistant HSV-1 as well as HSV-1/F and HSV-2/333. Plaque numbers and intracellular virions were significantly reduced by simultaneous knockdown of UL18 and UL19. The total intracellular viral genome loads were also significantly decreased in the UL18 and UL19 knockdown groups compared with the viral control. In conclusion, interfering with UL18 and UL19 gene expression could inhibit HSV-1 replication efficiently in vitro. Our research offers new targets for an RNA interference-based therapeutic strategy against HSV-1.