scholarly journals Proteomic profiling of human liver biopsies: Hepatitis C virus-induced fibrosis and mitochondrial dysfunction

Hepatology ◽  
2007 ◽  
Vol 46 (3) ◽  
pp. 649-657 ◽  
Author(s):  
Deborah L. Diamond ◽  
Jon M. Jacobs ◽  
Bryan Paeper ◽  
Sean C. Proll ◽  
Marina A. Gritsenko ◽  
...  
2004 ◽  
Vol 85 (11) ◽  
pp. 3173-3188 ◽  
Author(s):  
Peter Simmonds

In the 15 years since the discovery of hepatitis C virus (HCV), much has been learned about its role as a major causative agent of human liver disease and its ability to persist in the face of host-cell defences and the immune system. This review describes what is known about the diversity of HCV, the current classification of HCV genotypes within the family Flaviviridae and how this genetic diversity contributes to its pathogenesis. On one hand, diversification of HCV has been constrained by its intimate adaptation to its host. Despite the >30 % nucleotide sequence divergence between genotypes, HCV variants nevertheless remain remarkably similar in their transmission dynamics, persistence and disease development. Nowhere is this more evident than in the evolutionary conservation of numerous evasion methods to counteract the cell's innate antiviral defence pathways; this series of highly complex virus–host interactions may represent key components in establishing its ‘ecological niche’ in the human liver. On the other hand, the mutability and large population size of HCV enables it to respond very rapidly to new selection pressures, manifested by immune-driven changes in T- and B-cell epitopes that are encountered on transmission between individuals with different antigen-recognition repertoires. If human immunodeficiency virus type 1 is a precedent, future therapies that target virus protease or polymerase enzymes may also select very rapidly for antiviral-resistant mutants. These contrasting aspects of conservatism and adaptability provide a fascinating paradigm in which to explore the complex selection pressures that underlie the evolution of HCV and other persistent viruses.


Gut ◽  
1974 ◽  
Vol 15 (4) ◽  
pp. 260-267 ◽  
Author(s):  
J. OD. McGee ◽  
R. S. Patrick ◽  
M. C. Rodger ◽  
C. M. Luty

Virology ◽  
2003 ◽  
Vol 314 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Hideki Aizaki ◽  
Seishi Nagamori ◽  
Mami Matsuda ◽  
Hayato Kawakami ◽  
Osamu Hashimoto ◽  
...  

PROTEOMICS ◽  
2004 ◽  
Vol 4 (7) ◽  
pp. 2111-2116 ◽  
Author(s):  
Yuichiro Yokoyama ◽  
Yasuhiro Kuramitsu ◽  
Motonari Takashima ◽  
Norio Iizuka ◽  
Toshifusa Toda ◽  
...  

1998 ◽  
Vol 46 (5) ◽  
pp. 653-660 ◽  
Author(s):  
Francine M. Walker ◽  
Marie-Christine Dazza ◽  
Marie-Christine Dauge ◽  
Olivier Boucher ◽  
Christophe Bedel ◽  
...  

Hepatitis C virus (HCV) detection in the livers of chronically infected patients remains a debatable issue. We used immunohistochemistry, in situ hybridization (ISH) alone or after microwave heating with FITC-labeled probes, RT-PCR with unlabeled primers followed by ISH (RT-PCR-ISH), and in situ RT-PCR with FITC-labeled primers (in situ RT-PCRd) to localize the virus in 38 liver biopsy specimens from 21 chronically infected HCV patients treated with interferon-α (IFN-α). Biopsies were taken at the beginning and end of IFN-α treatment and 1 year later. Results were compared with that of HCV-PCR in serum. RT-PCR-ISH and in situ RT-PCRd showed HCV signal in all liver biopsies even in responders with seronegative HCV PCR. This signal was intranuclear, diffuse, or peripheral, in hepatocytes, bile ductule cells, and lymphocytes. Cytoplasmic signals were occasionally observed. Whereas the percentage of labeled hepatocytes remained constant, the number of labeled lymphoid follicles decreased after INF-α therapy. Immunohistochemistry resulted in the same pattern of positivity but it was weaker and inconstant. This study indicates the persistency of HCV latency in IFN-α responders 1 year after IFN-α treatment cessation, a finding that certainly deserves confirmation.


2009 ◽  
Vol 17 (11) ◽  
pp. 784-793 ◽  
Author(s):  
T. Wang ◽  
R. V. Campbell ◽  
M. K. Yi ◽  
S. M. Lemon ◽  
S. A. Weinman

2004 ◽  
Vol 78 (3) ◽  
pp. 1448-1455 ◽  
Author(s):  
Jie Zhang ◽  
Glenn Randall ◽  
Adrian Higginbottom ◽  
Peter Monk ◽  
Charles M. Rice ◽  
...  

ABSTRACT CD81 has been described as a putative receptor for hepatitis C virus (HCV); however, its role in HCV cell entry has not been characterized due to the lack of an efficient cell culture system. We have examined the role of CD81 in HCV glycoprotein-dependent entry by using a recently developed retroviral pseudotyping system. Human immunodeficiency virus (HIV) pseudotypes bearing HCV E1E2 glycoproteins show a restricted tropism for human liver cell lines. Although all of the permissive cell lines express CD81, CD81 expression alone is not sufficient to allow viral entry. CD81 is required for HIV-HCV pseudotype infection since (i) a monoclonal antibody specific for CD81 inhibited infection of susceptible target cells and (ii) silencing of CD81 expression in Huh-7.5 hepatoma cells by small interfering RNAs inhibited HIV-HCV pseudotype infection. Furthermore, expression of CD81 in human liver cells that were previously resistant to infection, HepG2 and HH29, conferred permissivity of HCV pseudotype infection. The characterization of chimeric CD9/CD81 molecules confirmed that the large extracellular loop of CD81 is a determinant for viral entry. These data suggest a functional role for CD81 as a coreceptor for HCV glycoprotein-dependent viral cell entry.


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