PMID- 36920600
OWN - NLM
STAT- MEDLINE
DCOM- 20230320
LR  - 20230418
IS  - 1432-8798 (Electronic)
IS  - 0304-8608 (Print)
IS  - 0304-8608 (Linking)
VI  - 168
IP  - 4
DP  - 2023 Mar 15
TI  - Hepatitis C virus nonstructural protein 4B induces lipogenesis via the Hippo 
      pathway.
PG  - 113
LID - 10.1007/s00705-023-05743-4 [doi]
LID - 113
AB  - Hepatitis C virus (HCV) infection causes abnormal lipid metabolism in 
      hepatocytes, which leads to hepatic steatosis and even hepatocellular carcinoma. 
      HCV nonstructural protein 4B (NS4B) has been reported to induce lipogenesis, but 
      the underlying mechanism is unclear. In this study, western blots were performed 
      to investigate the effect of NS4B protein levels on key effectors of the Hippo 
      and AKT signaling pathways. Yes-associated protein (YAP) and 
      moesin-ezrin-radixin-like protein (Merlin) are effectors of the Hippo pathway. 
      NS4B downregulated Merlin and phosphorylated YAP (p-YAP) protein expression while 
      increasing the expression of the key AKT pathway proteins p-AKT and NF-kappaB. By 
      observing the levels of AKT pathway proteins when Merlin was overexpressed or 
      silenced, it was determined that Merlin mediates the AKT pathway. We suggest that 
      HCV NS4B may mediate the AKT signaling pathway by inhibiting the Hippo pathway. 
      Lipid droplets were observed in Huh7.5 cells overexpressing NS4B, and they 
      increased significantly in number when Merlin was silenced. Overexpression of 
      NS4B and Merlin silencing enhanced the expression of sterol regulatory element 
      binding proteins (SREBPs), which have been demonstrated to be key regulatory 
      factors controlling fatty acid synthesis. NS4B and Merlin silencing also enhanced 
      the in vitro proliferative capacity of hepatocellular carcinoma cells. In 
      conclusion, NS4B induces lipogenesis via the effect of the Hippo-YAP pathway on 
      the AKT signaling pathway and thereby plays a significant role in the 
      pathogenesis of HCV-associated diseases.
CI  - (c) 2023. The Author(s).
FAU - Zou, Chen
AU  - Zou C
AUID- ORCID: 0000-0003-1700-8917
AD  - Department of Pathology, The First Affiliated Hospital, Jinan University, 
      Guangzhou, 510630, China. chris_zou@163.com.
AD  - Center for Medical Experiments, University of Chinese Academy of 
      Sciences-Shenzhen Hospital, Shenzhen, 518016, China. chris_zou@163.com.
FAU - Tan, Hongxi
AU  - Tan H
AD  - Center for Medical Experiments, University of Chinese Academy of 
      Sciences-Shenzhen Hospital, Shenzhen, 518016, China.
FAU - Zeng, Jun
AU  - Zeng J
AD  - Center for Medical Experiments, University of Chinese Academy of 
      Sciences-Shenzhen Hospital, Shenzhen, 518016, China.
FAU - Liu, Minqi
AU  - Liu M
AD  - Center for Medical Experiments, University of Chinese Academy of 
      Sciences-Shenzhen Hospital, Shenzhen, 518016, China.
FAU - Zhang, Guangping
AU  - Zhang G
AD  - Huadu District People's Hospital of Guangzhou, Guangzhou, 510600, China.
FAU - Zheng, Yi
AU  - Zheng Y
AD  - Center for Medical Experiments, University of Chinese Academy of 
      Sciences-Shenzhen Hospital, Shenzhen, 518016, China.
FAU - Zhang, Zhanfeng
AU  - Zhang Z
AD  - Department of Laboratory Science, First Affiliated Hospital of Guangzhou 
      University of Chinese Medicine, Guangzhou, 510600, China. 
      zhangzhanfeng90612@gzucm.edu.cn.
LA  - eng
GR  - JCYJ20170307093557440/Shenzhen Science and Technology Innovation Commission/
GR  - 201804010150/Science and Technology Program of Guangzhou/
GR  - 2020R01072/Science and Technology Innovation Bureau of Guangming/
PT  - Journal Article
DEP - 20230315
PL  - Austria
TA  - Arch Virol
JT  - Archives of virology
JID - 7506870
RN  - 0 (Neurofibromin 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Humans
MH  - Hepacivirus/genetics/metabolism
MH  - Hippo Signaling Pathway
MH  - Lipogenesis
MH  - Neurofibromin 2/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - *Carcinoma, Hepatocellular/genetics
MH  - Viral Nonstructural Proteins/genetics/metabolism
MH  - *Hepatitis C/genetics/metabolism
MH  - *Liver Neoplasms
PMC - PMC10017664
COIS- The authors declare no conflict of interest.
EDAT- 2023/03/16 06:00
MHDA- 2023/03/21 06:00
PMCR- 2023/03/15
CRDT- 2023/03/15 12:18
PHST- 2022/10/13 00:00 [received]
PHST- 2023/02/07 00:00 [accepted]
PHST- 2023/03/15 12:18 [entrez]
PHST- 2023/03/16 06:00 [pubmed]
PHST- 2023/03/21 06:00 [medline]
PHST- 2023/03/15 00:00 [pmc-release]
AID - 10.1007/s00705-023-05743-4 [pii]
AID - 5743 [pii]
AID - 10.1007/s00705-023-05743-4 [doi]
PST - epublish
SO  - Arch Virol. 2023 Mar 15;168(4):113. doi: 10.1007/s00705-023-05743-4.