PMID- 11358713
OWN - NLM
STAT- MEDLINE
DCOM- 20010628
LR  - 20191104
IS  - 1286-4579 (Print)
IS  - 1286-4579 (Linking)
VI  - 3
IP  - 3
DP  - 2001 Mar
TI  - Ultrastructural observations in hepatitis C virus-infected lymphoid cells.
PG  - 193-202
AB  - It is currently unclear whether the hepatocellular damage in chronic hepatitis C 
      virus (HCV) infection is produced through the intrahepatic action of the anti-HCV 
      immune response or through a direct cytopathic effect. In order to investigate 
      the features of HCV replication (morphogenesis and cytopathic effect), we studied 
      the infection of a permissive lymphocytic B cell line, Daudi cells, which were 
      infected with sera of HCV-positive patients, and were examined after various time 
      points under electron microscope. Viral genomic RNA was detected by in situ 
      hybridization, and apoptosis with the terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) method. The amount of viral 
      genomic RNA was observed to increase during infection. HCV replicated rapidly, 
      since characteristics of viral morphogenesis resembling those of yellow fever 
      virus in a hepatoma cell line could be found 2 days after infection. These 
      included the following: a) several viral particles identical in size (about 42 
      nm) and structure (a spherical 30-nm-sized electron-dense nucleocapsid surrounded 
      by a membrane) to yellow fever virus were present in the cytoplasm of cells 
      displaying already typical signs of the early stage of apoptosis; b) numerous 
      membrane-bound organelles and in particular the endoplasmic reticulum and 
      vacuoles were observed; c) proliferation of membranes was apparent; and d) 
      intracytoplasmic electron-dense inclusion bodies which have been demonstrated to 
      correspond to nucleocapsids for other flaviviruses were detected. Several cells 
      presented electron-dense areas in the endoplasmic reticulum displaying 30-nm 
      circular structures lying among an amorphous material. Striking cytopathic 
      features with ballooning, extremely enlarged vacuoles and signs of apoptosis were 
      found in cells often containing sequestered aggregates of virus-like particles. 
      By in situ hybridization we found that such enlarged cells contained HCV RNA. Our 
      results thus indicate that the ultrastructural features of HCV viral particles 
      and their morphogenesis resemble that of yellow fever virus and dengue virus. In 
      Daudi cells, HCV infection seems to rapidly trigger apoptotic cell death, and 
      efficient release of viral particles does not seem to take place.
FAU - Steffan, A
AU  - Steffan A
AD  - Laboratoire de virologie de la faculte de medecine de Strasbourg, Inserm U74, 3, 
      rue Koeberle, 67000, Strasbourg, France. Anne-Marie.Steffan@viro-ulp.u-strasbg.fr
FAU - Marianneau, P
AU  - Marianneau P
FAU - Caussin-Schwemling, C
AU  - Caussin-Schwemling C
FAU - Royer, C
AU  - Royer C
FAU - Schmitt, C
AU  - Schmitt C
FAU - Jaeck, D
AU  - Jaeck D
FAU - Wolf, P
AU  - Wolf P
FAU - Gendrault, J
AU  - Gendrault J
FAU - Stoll-Keller, F
AU  - Stoll-Keller F
LA  - eng
PT  - Journal Article
PL  - France
TA  - Microbes Infect
JT  - Microbes and infection
JID - 100883508
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Apoptosis
MH  - Cytopathogenic Effect, Viral
MH  - Hepacivirus/genetics/isolation & purification/*ultrastructure
MH  - Humans
MH  - In Situ Hybridization
MH  - Microscopy, Electron
MH  - RNA, Viral/analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Cells, Cultured/pathology/*ultrastructure/*virology
EDAT- 2001/05/19 10:00
MHDA- 2001/06/29 10:01
CRDT- 2001/05/19 10:00
PHST- 2001/05/19 10:00 [pubmed]
PHST- 2001/06/29 10:01 [medline]
PHST- 2001/05/19 10:00 [entrez]
AID - S1286457901013697 [pii]
AID - 10.1016/s1286-4579(01)01369-7 [doi]
PST - ppublish
SO  - Microbes Infect. 2001 Mar;3(3):193-202. doi: 10.1016/s1286-4579(01)01369-7.