Hepacivirus

VIRION

Enveloped, spherical, about 50 nm in diameter. Mature virions contain two virus-encoded membrane proteins (E1 and E2) in addition to the capsid protein.

GENOME

Monopartite, linear, ssRNA(+) genome of about 10 kb. The genome 3’ terminus is not polyadenylated but forms a loop structure. There is an internal ribosome entry site at the 5’ end that mediates translation initiation.

GENE EXPRESSION

The virion RNA is infectious and serves as both the genome and the viral messenger RNA. The whole genome is translated in a polyprotein, which is processed co- and post-translationally by host and viral proteases.

REPLICATION

  1. Attachement of the viral envelope protein E to host receptors mediates internalization into the host cell by clathrin-mediated endocytosis.
  2. Fusion of virus membrane with host endosomal membrane. RNA genome is released into the cytoplasm.
  3. The positive-sense genomic ssRNA is translated into a polyprotein, which is cleaved into all structural and non structural proteins (to yield the replication proteins).
  4. Replication takes place at the surface of endoplasmic reticulum in cytoplasmic viral factories. A dsRNA genome is synthesized from the genomic ssRNA(+). Host miRNA mir-122 plays a essential role in initiating replication.
  5. The dsRNA genome is transcribed/replicated thereby providing viral mRNAs/new ssRNA(+) genomes.
  6. Virus assembly occurs at the endoplasmic reticulum and seems to be facilitated by the viral ionic channel p7. The virion buds via the host ESCRT complexes at the endoplasmic reticulum, is transported to the Golgi apparatus, and then exits the cell via the secretory pathway.

Host-virus interaction

Apoptosis modulation

Flaviviruses NS3 induces apoptosis through host caspases activation

Autophagy modulation

Flaviviruses NS4A and NS4B induces autophagy signaling .

Cell-cycle modulation

Hepatitis C virus induces down-regulation of the retinoblastoma tumor suppressor and G1/S host cell cycle checkpoint dysregulation .

Innate immune response inhibition

Hepatitis C virus inhibits the interferon signaling pathway by blocking the IFN receptors , STAT1 and TYK2 .
Hepatitis C virus inhibits the host IFN-mediated response by blocking host MAVS , TRAFs and TBK1-IKBKE-DDX3 complex .

Host gene expression shutoff by virus

Hepatitis C virus activates PKR about 12h p.i. to shutoff host translation through the PKR-mediated phosphorylation of the eIF2alpha initiation factor .

Matching UniProtKB/Swiss-Prot entries

34 entries grouped by strain (browse by keywords)

2 entries

Hepatitis C virus genotype 1a (isolate H) (HCV) reference strain

Select_all Deselect_all  
F_HCVHF protein (Alternate reading frame protein/F-protein) (ARFP/F) (Frameshifted ...
POLG_HCVHGenome polyprotein

2 entries

Hepatitis C virus genotype 1a (isolate 1) (HCV)

Select_all Deselect_all  
F_HCV1F protein (Alternate reading frame protein/F-protein) (ARFP/F) (Frameshifted ...
POLG_HCV1Genome polyprotein

1 entry

Hepatitis C virus genotype 1b (isolate BK) (HCV)

1 entry

Hepatitis C virus genotype 1b (isolate Con1) (HCV)

1 entry

Hepatitis C virus genotype 1b (isolate HC-J1) (HCV)


POLG_HCVJ1Genome polyprotein

1 entry

Hepatitis C virus genotype 1b (isolate HC-JT) (HCV)


POLG_HCVJTGenome polyprotein

1 entry

Hepatitis C virus genotype 1b (isolate HCR6) (HCV)


POLG_HCVR6Genome polyprotein

1 entry

Hepatitis C virus genotype 1b (isolate Japanese) (HCV)

1 entry

Hepatitis C virus genotype 1b (isolate Taiwan) (HCV)


POLG_HCVTWGenome polyprotein

1 entry

Hepatitis C virus genotype 1b (strain HC-J4) (HCV)

1 entry

Hepatitis C virus genotype 1c (isolate HC-G9) (HCV)


POLG_HCVH9Genome polyprotein

1 entry

Hepatitis C virus genotype 1c (isolate India) (HCV)


POLG_HCVINGenome polyprotein

1 entry

Hepatitis C virus genotype 2a (isolate HC-J6) (HCV)


POLG_HCVJ6Genome polyprotein

1 entry

Hepatitis C virus genotype 2a (isolate JFH-1) (HCV)

1 entry

Hepatitis C virus genotype 2b (isolate HC-J8) (HCV)


POLG_HCVJ8Genome polyprotein

1 entry

Hepatitis C virus genotype 2b (isolate JPUT971017) (HCV)


POLG_HCVJPGenome polyprotein

1 entry

Hepatitis C virus genotype 2c (isolate BEBE1) (HCV)


POLG_HCVBBGenome polyprotein

1 entry

Hepatitis C virus genotype 2k (isolate VAT96) (HCV)


POLG_HCVVAGenome polyprotein

1 entry

Hepatitis C virus genotype 3a (isolate NZL1) (HCV)


POLG_HCVNZGenome polyprotein

1 entry

Hepatitis C virus genotype 3a (isolate k3a) (HCV)


POLG_HCVK3Genome polyprotein

1 entry

Hepatitis C virus genotype 3b (isolate Tr-Kj) (HCV)


POLG_HCVTRGenome polyprotein

1 entry

Hepatitis C virus genotype 3k (isolate JK049) (HCV)


POLG_HCVJKGenome polyprotein

1 entry

Hepatitis C virus genotype 4a (isolate ED43) (HCV)


POLG_HCVEDGenome polyprotein

1 entry

Hepatitis C virus genotype 5a (isolate EUH1480) (HCV)


POLG_HCVEVGenome polyprotein

1 entry

Hepatitis C virus genotype 5a (isolate SA13) (HCV)


POLG_HCVSAGenome polyprotein

1 entry

Hepatitis C virus genotype 6a (isolate 6a33) (HCV)


POLG_HCV6AGenome polyprotein

1 entry

Hepatitis C virus genotype 6a (isolate EUHK2) (HCV)


POLG_HCVEUGenome polyprotein

1 entry

Hepatitis C virus genotype 6b (isolate Th580) (HCV)


POLG_HCVT5Genome polyprotein

1 entry

Hepatitis C virus genotype 6d (isolate VN235) (HCV)


POLG_HCVVNGenome polyprotein

1 entry

Hepatitis C virus genotype 6g (isolate JK046) (HCV)


POLG_HCVJLGenome polyprotein

1 entry

Hepatitis C virus genotype 6h (isolate VN004) (HCV)


POLG_HCVVPGenome polyprotein

1 entry

Hepatitis C virus genotype 6k (isolate VN405) (HCV)


POLG_HCVVOGenome polyprotein