PMID- 28768874
OWN - NLM
STAT- MEDLINE
DCOM- 20171024
LR  - 20220818
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 91
IP  - 20
DP  - 2017 Oct 15
TI  - PGC1alpha Transcriptional Adaptor Function Governs Hepatitis B Virus Replication by 
      Controlling HBcAg/p21 Protein-Mediated Capsid Formation.
LID - 10.1128/JVI.00790-17 [doi]
LID - e00790-17
AB  - In the human hepatoma cell line Huh7, the coexpression of the coactivators 
      peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha), cyclic 
      AMP-responsive element binding protein binding protein (CBP), steroid receptor 
      coactivator 1 (SRC1), and protein arginine methyltransferase 1 (PRMT1) only 
      modestly increase hepatitis B virus (HBV) biosynthesis. However, by utilizing the 
      human embryonic kidney cell line HEK293T, it was possible to demonstrate that 
      PGC1alpha alone can support viral biosynthesis independently of the expression of 
      additional coactivators or transcription factors. In contrast, additional 
      coactivators failed to support robust HBV replication in the absence of PGC1alpha. 
      These observations indicate that PGC1alpha represents a novel adaptor molecule 
      capable of recruiting the necessary transcriptional machinery to the HBV 
      nucleocapsid promoter to modestly enhance viral pregenomic 3.5-kb RNA synthesis. 
      Although this change in transcription is associated with a similar modest change 
      in hepatitis B virus core antigen polypeptide (HBcAg/p21) synthesis, it mediates 
      a dramatic increase in viral capsid production and robust viral replication. 
      Therefore, it is apparent that the synthesis of cytoplasmic HBcAg/p21 above a 
      critical threshold level is required for the efficient assembly of HBV 
      replication-competent viral capsids.IMPORTANCE Hepatitis B virus (HBV) is a major 
      human pathogen, and novel targets for the development of additional therapeutic 
      agents are urgently needed. Here we demonstrate that the coactivator peroxisome 
      proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha) serves as a unique 
      adaptor molecule for the recruitment of additional coactivator proteins, which 
      can finely regulate HBV transcription. The consequence of this precise regulation 
      of viral RNA levels by PGC1alpha is a subtle increase in cytoplasmic HBcAg/p21 
      polypeptide translation, which shifts the equilibrium from dimer formation 
      dramatically in favor of viral capsid assembly. These findings suggest that both 
      PGC1alpha and capsid assembly may represent attractive targets for the development of 
      antiviral agents against chronic HBV infection.
CI  - Copyright (c) 2017 American Society for Microbiology.
FAU - Shalaby, Rasha E
AU  - Shalaby RE
AD  - Department of Microbiology and Immunology, College of Medicine, University of 
      Illinois at Chicago, Chicago, Illinois, USA.
FAU - Iram, Saira
AU  - Iram S
AD  - Department of Microbiology and Immunology, College of Medicine, University of 
      Illinois at Chicago, Chicago, Illinois, USA.
FAU - Cakal, Bulent
AU  - Cakal B
AD  - Department of Microbiology, Istanbul Faculty of Medicine, Istanbul University, 
      Istanbul, Turkey.
FAU - Oropeza, Claudia E
AU  - Oropeza CE
AD  - Department of Microbiology and Immunology, College of Medicine, University of 
      Illinois at Chicago, Chicago, Illinois, USA.
FAU - McLachlan, Alan
AU  - McLachlan A
AD  - Department of Microbiology and Immunology, College of Medicine, University of 
      Illinois at Chicago, Chicago, Illinois, USA mclach@uic.edu.
LA  - eng
GR  - R01 AI125401/AI/NIAID NIH HHS/United States
GR  - R01 CA238328/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170927
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Capsid Proteins)
RN  - 0 (Hepatitis B Core Antigens)
RN  - 0 (PPARGC1A protein, human)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Capsid/*metabolism
MH  - Capsid Proteins/genetics
MH  - Cell Line, Tumor
MH  - DNA Replication
MH  - HEK293 Cells
MH  - Hepatitis B Core Antigens/*metabolism
MH  - Hepatitis B virus/genetics/*physiology
MH  - Hepatocytes/virology
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 
      1-alpha/genetics/*metabolism
MH  - RNA, Viral/genetics/metabolism
MH  - Transcription, Genetic
MH  - Virus Assembly
MH  - *Virus Replication
PMC - PMC5625508
OTO - NOTNLM
OT  - PGC1alpha
OT  - capsid assembly
OT  - hepatitis B virus
OT  - transcriptional coactivators
EDAT- 2017/08/05 06:00
MHDA- 2017/10/25 06:00
PMCR- 2018/03/27
CRDT- 2017/08/04 06:00
PHST- 2017/05/10 00:00 [received]
PHST- 2017/07/30 00:00 [accepted]
PHST- 2017/08/05 06:00 [pubmed]
PHST- 2017/10/25 06:00 [medline]
PHST- 2017/08/04 06:00 [entrez]
PHST- 2018/03/27 00:00 [pmc-release]
AID - JVI.00790-17 [pii]
AID - 00790-17 [pii]
AID - 10.1128/JVI.00790-17 [doi]
PST - epublish
SO  - J Virol. 2017 Sep 27;91(20):e00790-17. doi: 10.1128/JVI.00790-17. Print 2017 Oct 
      15.