PMID- 33397935
OWN - NLM
STAT- MEDLINE
DCOM- 20210114
LR  - 20240226
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Jan 4
TI  - Hepatitis B virus rigs the cellular metabolome to avoid innate immune 
      recognition.
PG  - 98
LID - 10.1038/s41467-020-20316-8 [doi]
LID - 98
AB  - Glucose metabolism and innate immunity evolved side-by-side. It is unclear if and 
      how the two systems interact with each other during hepatitis B virus (HBV) 
      infections and, if so, which mechanisms are involved. Here, we report that HBV 
      activates glycolysis to impede retinoic acid-inducible gene I (RIG-I)-induced 
      interferon production. We demonstrate that HBV sequesters MAVS from RIG-I by 
      forming a ternary complex including hexokinase (HK). Using a series of 
      pharmacological and genetic approaches, we provide in vitro and in vivo evidence 
      indicating that HBV suppresses RLR signaling via lactate 
      dehydrogenase-A-dependent lactate production. Lactate directly binds MAVS 
      preventing its aggregation and mitochondrial localization during HBV infection. 
      Therefore, we show that HK2 and glycolysis-derived lactate have important 
      functions in the immune escape of HBV and that energy metabolism regulates innate 
      immunity during HBV infection.
FAU - Zhou, Li
AU  - Zhou L
AUID- ORCID: 0000-0002-6736-0057
AD  - State Key Laboratory of Virology, Modern Virology Research Center, College of 
      Life Sciences, Wuhan University, Wuhan, 430072, China.
FAU - He, Rui
AU  - He R
AD  - State Key Laboratory of Virology, Modern Virology Research Center, College of 
      Life Sciences, Wuhan University, Wuhan, 430072, China.
FAU - Fang, Peining
AU  - Fang P
AD  - State Key Laboratory of Virology, Modern Virology Research Center, College of 
      Life Sciences, Wuhan University, Wuhan, 430072, China.
FAU - Li, Mengqi
AU  - Li M
AD  - State Key Laboratory of Virology, Modern Virology Research Center, College of 
      Life Sciences, Wuhan University, Wuhan, 430072, China.
FAU - Yu, Haisheng
AU  - Yu H
AD  - State Key Laboratory of Virology, Modern Virology Research Center, College of 
      Life Sciences, Wuhan University, Wuhan, 430072, China.
FAU - Wang, Qiming
AU  - Wang Q
AUID- ORCID: 0000-0002-9386-5091
AD  - College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, 
      410128, China.
FAU - Yu, Yi
AU  - Yu Y
AD  - The Key Laboratory of Biosystems Homeostasis and Protection of the Ministry of 
      Education and Innovation Center for Cell Signaling Network, Life Sciences 
      Institute, Zhejiang University, Hangzhou, China.
FAU - Wang, Fubing
AU  - Wang F
AD  - Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 
      China.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, 
      College of Food and Pharmaceutical Engineering, Hubei University of Technology, 
      Wuhan, 430068, China.
FAU - Chen, Aidong
AU  - Chen A
AD  - Department of Physiology, Nanjing Medical University, Nanjing, 211166, China.
FAU - Peng, Nanfang
AU  - Peng N
AD  - State Key Laboratory of Virology, Modern Virology Research Center, College of 
      Life Sciences, Wuhan University, Wuhan, 430072, China.
FAU - Lin, Yong
AU  - Lin Y
AD  - The Key Laboratory of Molecular Biology of Infectious Diseases designated by the 
      Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
FAU - Zhang, Rui
AU  - Zhang R
AD  - Department of Hepato-Pancreato-Biliary Surgery, SunYat-sen Memorial Hospital, 
      SunYat-sen University, Guangzhou, 510120, China.
FAU - Trilling, Mirko
AU  - Trilling M
AUID- ORCID: 0000-0003-3659-3541
AD  - Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 
      Essen, 45122, Germany.
FAU - Broering, Ruth
AU  - Broering R
AUID- ORCID: 0000-0002-7125-3246
AD  - Department of Gastroenterology and Hepatology, University Hospital Essen, 
      University of Duisburg-Essen, Essen, 45122, Germany.
FAU - Lu, Mengji
AU  - Lu M
AD  - Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 
      Essen, 45122, Germany.
FAU - Zhu, Ying
AU  - Zhu Y
AD  - State Key Laboratory of Virology, Modern Virology Research Center, College of 
      Life Sciences, Wuhan University, Wuhan, 430072, China.
FAU - Liu, Shi
AU  - Liu S
AUID- ORCID: 0000-0002-9289-0631
AD  - State Key Laboratory of Virology, Modern Virology Research Center, College of 
      Life Sciences, Wuhan University, Wuhan, 430072, China. liushi_liushi@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210104
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (MAVS protein, human)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 9008-11-1 (Interferons)
RN  - EC 3.6.4.13 (DEAD Box Protein 58)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Anaerobiosis
MH  - Animals
MH  - Cells, Cultured
MH  - DEAD Box Protein 58/metabolism
MH  - Glucose/metabolism
MH  - Glycolysis
MH  - Hep G2 Cells
MH  - Hepatitis B virus/*physiology
MH  - Hepatocytes/metabolism/pathology/virology
MH  - Humans
MH  - Immune Evasion
MH  - *Immunity, Innate
MH  - Interferons/metabolism
MH  - Lactic Acid/metabolism
MH  - *Metabolome
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Signal Transduction
MH  - Virion/metabolism
MH  - Mice
PMC - PMC7782485
COIS- The authors declare no competing interests.
EDAT- 2021/01/06 06:00
MHDA- 2021/01/15 06:00
PMCR- 2021/01/04
CRDT- 2021/01/05 06:17
PHST- 2019/12/14 00:00 [received]
PHST- 2020/11/23 00:00 [accepted]
PHST- 2021/01/05 06:17 [entrez]
PHST- 2021/01/06 06:00 [pubmed]
PHST- 2021/01/15 06:00 [medline]
PHST- 2021/01/04 00:00 [pmc-release]
AID - 10.1038/s41467-020-20316-8 [pii]
AID - 20316 [pii]
AID - 10.1038/s41467-020-20316-8 [doi]
PST - epublish
SO  - Nat Commun. 2021 Jan 4;12(1):98. doi: 10.1038/s41467-020-20316-8.