Pterostilbene, an active constituent of blueberries, enhances innate immune activation and restricts enterovirus D68 infection

Qingran Yang; Huili Li; Zhaoxue Li; Jiaxin Yang; Zhe Zhang; Lili Zhang; Haoran Guo; Wei Wei

doi:10.3389/fimmu.2023.1118933

Pterostilbene, an active constituent of blueberries, enhances innate immune activation and restricts enterovirus D68 infection

Front Immunol. 2023 Feb 9:14:1118933. doi: 10.3389/fimmu.2023.1118933. eCollection 2023.

Authors

Qingran Yang¹, Huili Li¹, Zhaoxue Li¹, Jiaxin Yang¹, Zhe Zhang¹, Lili Zhang¹, Haoran Guo¹, Wei Wei^{1

2}

Affiliations

¹ Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Translational Medicine, First Hospital, Jilin University, Changchun, Jilin, China.
² Institute of Virology and Acquired Immune Deficiency Syndrome (AIDS) Research, First Hospital, Jilin University, Changchun, Jilin, China.

Abstract

Enterovirus D68 (EV-D68) is a globally re-emerging respiratory pathogen implicated in outbreaks of severe respiratory illnesses and associated with acute flaccid myelitis. However, effective vaccines or treatments for EV-D68 infections remain scarce. We demonstrated that the active constituent of blueberries, pterostilbene (Pte), and its major metabolite, pinostilbene (Pin), facilitated innate immune responses in EV-D68-infected human respiratory cells. Pte and Pin treatment clearly relieved EV-D68-triggered cytopathic effects. Importantly, both Pte and Pin disrupted viral RNA replication (EC₅₀ rank from 1.336 to 4.997 µM) and infectious virion production in a dose-dependent manner, without cytotoxicity at virucidal concentrations. Pte- or Pin-treated respiratory cells did not show any influences on EV-D68 entry but showed substantially decreased viral RNA replication and protein synthesis. Finally, we showed that Pte and Pin broadly suppressed the replication capacity of circulating EV-D68 strains isolated from recent pandemics. In summary, our results suggest that Pte and its derivative, Pin, enhance host immune recognition of EV-D68 and suppress EV-D68 replication, which represents a promising strategy for antiviral drug development.

Keywords: EV-D68; antivirals; innate immunity; interferon; pinostilbene; pterostilbene.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blueberry Plants*
Enterovirus D, Human*
Enterovirus Infections* / drug therapy
Humans
Immunity, Innate

Substances

pterostilbene

Grants and funding

This work was supported in part by funding from the National Natural Science Foundation of China (32222005, 82172246), the Department of Science and Technology of Jilin Province (No. 20190304033YY), the open project of Key Laboratory of Organ Regeneration and Transplantation, Ministry of Education, the Program for JLU Science and Technology Innovative Research Team (2017TD-08) and Fundamental Research Funds for the Central Universities.