Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma

Kim, KyeongJin; Kim, Kook Hwan; Ha, Eunsin; Park, Jin Young; Sakamoto, Naoya; Cheong, JaeHun

doi:10.1016/j.febslet.2009.07.034

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Volume 583, Issue 17 , Pages 2720-2726, 3 September 2009

Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma

Edited by Hans-Dieter Klenk

KyeongJin Kim
- Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea
Kook Hwan Kim
- Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea
Eunsin Ha
- Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea
Jin Young Park
- Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea
Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
JaeHun Cheong
- Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea
- Corresponding author. Fax: +82 51 513 9258.

Received 11 July 2009; accepted 17 July 2009. published online 23 July 2009.

Abstract

Steatosis is an established risk factor for disease progression in cases of chronic hepatitis C. Recently it was demonstrated that Hepatitis C virus (HCV) core and non-structural (NS) 2 proteins (NS2) induce lipid accumulation in hepatic cells. However, it has yet to be determined whether other HCV proteins are associated with lipid metabolism. The NS5A augmented the transcriptional activity and gene expression of PPARγ. Furthermore, NS5A increased the ability to recruit the transcriptional coactivator PGC-1s to the PPRE with PPARγ, as well as the interaction with PPARγ2 and PGC-1α. Our results indicate that NS5A may exploit multiple strategies that enhance PPARγ-induced lipid accumulation.

Structured summary

MINT-7229685: PPAR gamma 2 (uniprotkb:P37231-2) physically interacts (MI:0914) with PGC1 alpha (uniprotkb:Q9UBK2) by pull down (MI:0096)

MINT-7229712: PPAR gamma 2 (uniprotkb:P37231-2) physically interacts (MI:0914) with NS5A (uniprotkb:P26662) by pull down (MI:0096)

MINT-7229698: PPAR gamma 2 (uniprotkb:P37231-2) physically interacts (MI:0914) with PGC1 alpha (uniprotkb:Q9UBK2) by anti tag coimmunoprecipitation (MI:0007)

MINT-7229731: PPAR gamma 2 (uniprotkb:P37231-2) physically interacts (MI:0914) with NS5A (uniprotkb:P26662) by anti tag coimmunoprecipitation (MI:0007)

Keywords: Hepatitis C virus, NS5A, Lipid accumulation, PGC-1, PPARγ