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Hepatitis C virus–cell interactions and their role in pathogenesis

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1 Hepatitis C virus–cell interactions and their role in pathogenesis
Stephen J Polyak, PhD  Clinics in Liver Disease  Volume 7, Issue 1, Pages (February 2003) DOI: /S (02)

2 Fig. 1 The HCV life cycle. In the first step, HCV binds to and enters cells. This step may be mediated by interaction of HCV glycoproteins with CD81 and LDLR. HCV then is uncoated in acidic endosomes (H+) where replication occurs. Replication involves multiple virus–virus and virus–host interactions that regulate HCV polyprotein production and processing, and genome (+RNA) versus antigenome synthesis. HCV proteins accumulated in the endoplasmic reticulum (ER) and Golgi apparatus, where assembly and release of progeny viruses, occur. Abbreviations: RdRP, RNA dependent RNA polymerase; Rep, HCV replicase complex. Clinics in Liver Disease 2003 7, 67-88DOI: ( /S (02) )

3 Fig. 2 Localization of HCV proteins in human cells. NS5A (left panel) and core (right panel) proteins were expressed in human osteosarcoma and hepatocytes (Huh7) cells, respectively, and immunofluorescent detection of the proteins was performed. As can be seen, both proteins are located primarily in the cytoplasm, although small amounts of NS5A can be seen in the nucleus and core is associated with cytoplasmic lipid droplets. Clinics in Liver Disease 2003 7, 67-88DOI: ( /S (02) )

4 Fig. 3 NS5A (A) and core (B) structure function relationships. The top panel of each figure depicts the position of the gene in the context of the HCV polyprotein, along with major phosphorylation sites. Below each figure are the regions of each protein that are required for various activities including cytoplasmic retention (cyto) [72], interferon sensitivity determining region (ISDR) [90], PKR binding domain (PKR) [135], nuclear localization signal (NLS) [70], Grb2 binding domain (Grb2) [92], variable domains 3 [149] and 4 [85] (V3, V4). The domains required for binding cellular proteins and RNAs also are indicated. Clinics in Liver Disease 2003 7, 67-88DOI: ( /S (02) )

5 Fig. 3 NS5A (A) and core (B) structure function relationships. The top panel of each figure depicts the position of the gene in the context of the HCV polyprotein, along with major phosphorylation sites. Below each figure are the regions of each protein that are required for various activities including cytoplasmic retention (cyto) [72], interferon sensitivity determining region (ISDR) [90], PKR binding domain (PKR) [135], nuclear localization signal (NLS) [70], Grb2 binding domain (Grb2) [92], variable domains 3 [149] and 4 [85] (V3, V4). The domains required for binding cellular proteins and RNAs also are indicated. Clinics in Liver Disease 2003 7, 67-88DOI: ( /S (02) )


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