PMID- 11352669
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20131121
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 284
IP  - 1
DP  - 2001 May 25
TI  - The hepatitis C virus nonstructural protein 4B is an integral endoplasmic 
      reticulum membrane protein.
PG  - 70-81
AB  - The hepatitis C virus (HCV) nonstructural protein 4B (NS4B) is a relatively 
      hydrophobic 27-kDa protein of unknown function. A tetracycline-regulated gene 
      expression system, a novel monoclonal antibody, and in vitro 
      transcription-translation were employed to investigate the subcellular 
      localization and to characterize the membrane association of this viral protein. 
      When expressed individually or in the context of the entire HCV polyprotein, NS4B 
      was localized in the endoplasmic reticulum (ER), as shown by subcellular 
      fractionation, immunofluorescence analyses, and double-label confocal laser 
      scanning microscopy. In this compartment NS4B colocalized with the other HCV 
      nonstructural proteins. Association of NS4B with the ER membrane occurred 
      cotranslationally, presumably via engagement of the signal recognition particle 
      by an internal signal sequence. In membrane extraction and proteinase protection 
      assays NS4B displayed properties of a cytoplasmically oriented integral membrane 
      protein. Taken together, our findings suggest that NS4B is a component of a 
      membrane-associated cytoplasmic HCV replication complex. An efficient replication 
      system will be essential to further define the role of NS4B in the viral life 
      cycle.
CI  - Copyright 2001 Academic Press.
FAU - Hugle, T
AU  - Hugle T
AD  - Department of Medicine II, University of Freiburg, Freiburg, D-79106, Germany.
FAU - Fehrmann, F
AU  - Fehrmann F
FAU - Bieck, E
AU  - Bieck E
FAU - Kohara, M
AU  - Kohara M
FAU - Krausslich, H G
AU  - Krausslich HG
FAU - Rice, C M
AU  - Rice CM
FAU - Blum, H E
AU  - Blum HE
FAU - Moradpour, D
AU  - Moradpour D
LA  - eng
GR  - AI40034/AI/NIAID NIH HHS/United States
GR  - CA57973/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Membrane Proteins)
RN  - 0 (NS4 protein, hepatitis C virus)
RN  - 0 (Viral Nonstructural Proteins)
RN  - 0 (Viral Proteins)
RN  - F8VB5M810T (Tetracycline)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Endoplasmic Reticulum/*metabolism/virology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fluorescent Antibody Technique, Indirect
MH  - Gene Expression Regulation, Viral
MH  - Hepacivirus/*pathogenicity
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microscopy, Confocal
MH  - Protein Biosynthesis
MH  - Tetracycline/pharmacology
MH  - Transcription, Genetic
MH  - Viral Nonstructural Proteins/*metabolism
MH  - Viral Proteins/*metabolism
EDAT- 2001/05/16 10:00
MHDA- 2001/06/22 10:01
CRDT- 2001/05/16 10:00
PHST- 2001/05/16 10:00 [pubmed]
PHST- 2001/06/22 10:01 [medline]
PHST- 2001/05/16 10:00 [entrez]
AID - S0042-6822(01)90873-6 [pii]
AID - 10.1006/viro.2001.0873 [doi]
PST - ppublish
SO  - Virology. 2001 May 25;284(1):70-81. doi: 10.1006/viro.2001.0873.