{Reference Type}: Journal Article
{Title}: AMPK restricts HHV-6A replication by inhibiting glycolysis and mTOR signaling.
{Author}: Yang X;Tian S;Min Z;Garbarino E;Ma J;Jia J;Tang H;Li L;
{Journal}: Virology
{Volume}: 595
{Issue}: 0
{Year}: 2024 Jul 9
{Factor}: 3.513
{DOI}: 10.1016/j.virol.2024.110080
{Abstract}: AMP-activated protein kinase (AMPK) is a cellular energy sensor regulating metabolic homeostasis. 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.