Sirtuin Family의 일원인 Sirtuin 5 (SIRT5)는 주로 미토콘드리아에 존재하여, desuccinylase와 demalonylase 활동을 통해 세포 내에서 발생하는 다양한 대사 반응을 조절합니다. 즉, SIRT5는 세포의 에너지 생산 및 대사 조절에 중요한 영향을 미친다고 알려져 있습니다. B형 간염 바이러스 (hepatitis B virus, HBV) 증식에 대한 SIRT5의 효소 작용 효과는 아직 밝혀지지 않았습니다. 본 연구에서 저는 HBV가 증식하는 세포에서는 endogenous SIRT5가 감소한다는 것을 발견했습니다. SIRT5 Isoform 1 (SIRT5.1)를 과발현하면 HBV mRNA 전사 및 replicative intermediate (RI) DNA 합성이 감소됨과 동시에 AMPK (AMP-activated protein kinase)가 활성화되고 AKT (protein kinase B) 신호 전달 경로가 억제됩니다. 또한, AMPK를 과발현하면 SIRT5 활성화를 통해 AKT 신호 전달 경로를 억제하고 HBV mRNA 및 RI DNA를 감소시켰습니다. 이러한 결과는 HBV 증식이 SIRT5 활성을 억제하고, SIRT5.1 과발현이 AMPK 및 AKT신호 전달 경로를 통해 HBV 증식을 억제한다는 것을 보여줍니다. 따라서 SIRT5.1의 과발현은 HBV 감염에 대한 새로운 치료 표적이 될 수 있습니다._x000D_
<br>핵심어 : B형 간염 바이러스, B형 간염 바이러스 증식, SIRT5, SIRT5 Isoform 1, AMPK, AKT|Sirtuin 5 (SIRT5), a member of the Sirtuin family, is primarily localized in the mitochondria and regulates various cellular metabolic reactions through its desuccinylase and demalonylase activities. It is known that SIRT5 significantly influences cellular energy production and metabolic control. However, the effect of SIRT5's enzymatic activity on hepatitis B virus (HBV) replication has never been explored. In this study, I discovered that endogenous SIRT5 level is decreased by HBV replication. Overexpression of SIRT5 Isoform 1 (SIRT5.1) results in a reduction of HBV mRNA transcription and replicative intermediate (RI) DNA synthesis, along with the activation of AMP-activated protein kinase (AMPK) and inhibition of the AKT (protein kinase B) signaling pathway. Additionally, AMPK overexpression was found to activate SIRT5, leading to suppression of AKT signaling pathway and a decrease in HBV mRNA and RI DNA levels. These findings suggest that HBV replication suppresses SIRT5 activity, while SIRT5.1 overexpression inhibits HBV replication through the AMPK and AKT signaling pathways. Therefore, SIRT5.1 overexpression could be a potential therapeutic target for HBV infection._x000D_
<br>Keywords : HBV, HBV replication, SIRT5, SIRT5 Isoform 1, AMPK, AKT
Alternative Abstract
Sirtuin 5 (SIRT5), a member of the Sirtuin family, is primarily localized in the mitochondria and regulates various cellular metabolic reactions through its desuccinylase and demalonylase activities. It is known that SIRT5 significantly influences cellular energy production and metabolic control. However, the effect of SIRT5's enzymatic activity on hepatitis B virus (HBV) replication has never been explored. In this study, I discovered that endogenous SIRT5 level is decreased by HBV replication. Overexpression of SIRT5 Isoform 1 (SIRT5.1) results in a reduction of HBV mRNA transcription and replicative intermediate (RI) DNA synthesis, along with the activation of AMP-activated protein kinase (AMPK) and inhibition of the AKT (protein kinase B) signaling pathway. Additionally, AMPK overexpression was found to activate SIRT5, leading to suppression of AKT signaling pathway and a decrease in HBV mRNA and RI DNA levels. These findings suggest that HBV replication suppresses SIRT5 activity, while SIRT5.1 overexpression inhibits HBV replication through the AMPK and AKT signaling pathways. Therefore, SIRT5.1 overexpression could be a potential therapeutic target for HBV infection._x000D_
<br>Keywords : HBV, HBV replication, SIRT5, SIRT5 Isoform 1, AMPK, AKT
