AMPK restricts HHV-6A replication by inhibiting glycolysis and mTOR signaling

In this study, we investigated the role of AMPK in response to human herpesvirus 6A (HHV-6A) infection. We show that HHV-6A infection significantly downregulates the active phosphorylated state of AMPK in infected T cells. Pharmacological activation of AMPK highly attenuated HHV-6A propagation. Mechanistically, we found that the activation of AMPK by AICAR blocked HHV-6-induced glycolysis by inhibiting glucose metabolism and lactate secretion, as well as decreasing expressions of key glucose transporters and glycolytic enzymes. In addition, mTOR signaling has been inactivated in HHV-6A infected T cells by AICAR treatment. We also showed that HHV-6A infection of human umbilical cord blood mononuclear cells (CBMCs) reduced AMPK activity whereas the activation of AMPK by metformin drastically reduced HHV-6A DNA replication and virions production. Taken together, this study demonstrates that AMPK is a promising antiviral therapeutic target against HHV-6A infection.PMID:38631099 | DOI:10.1016/j.virol.2024.110080

Source: Virology - April 17, 2024 Category: Virology Authors: Xiaodi Yang Siyu Tian Zhujiang Min Emanuela Garbarino Jingjing Ma Junli Jia Huamin Tang Lingyun Li Source Type: research