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Hepacivirus (taxid:11102)

Hepacivirus is a genus of ssRNA+ viruses in the Flaviviridae family that infect the livers of mammals. In humans, HCV can cause hepatitis and, in rare cases, hepatocellular carcinoma.

VIRION

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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

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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 (IRES) 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.

ENZYMES

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 at the endoplasmic reticulum and is transported to the Golgi apparatus.
  7. Release of new virions by exocytosis.
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TAXONOMY Group IV; ssRNA positive-strand viruses
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Kitrinoviricota
Class: Flasuviricetes
Order:Amarillovirales
Family:Flaviviridae
Genus: Hepacivirus
VIRUS
REFERENCE STRAIN Hepatitis C virus
Sequence | Genome assembly | Proteome

Host

NATURAL HOSTS Human.
TROPISM Hepatocytes.
INTERACTIONS Cell receptors:
HCV: Heparan sulfate, LDL-R, CD81, CLDN1.
Host-virus interaction

Ecology and disease

GEOGRAPHY Worlwide.
ASSOCIATED DISEASES Hepatitis.
hepatocellular carcinoma
TRANSMISSION Sexual contact, blood.
VACCINE None
ANTIVIRAL DRUGS Ribavirin (Guanosine analog)
Interferon type I (Cytokine)
Peginterferon alfa2a (Cytokine)
Peginterferon alfa2b (Cytokine)
Alisporivir (Experimental, cyclophilin inhibitor)
Glecaprevir (NS3/4A protease inhibitor)
Grazoprevir (NS3/4A protease inhibitor)
Peritaprevir (NS3/4A protease inhibitor)
Simeprevir (NS3/4A protease inhibitor)
Daclatasvir (NS5A inhibitor)
Elbasvir (NS5A inhibitor)
Ombitasvir (NS5A inhibitor)
Pibrentasvir (NS5A inhibitor)
Elbasvir (NS5A inhibitor)
Velpatasvir (NS5A inhibitor)
Radalbuvir (Experimental, NS5B inhibitor)
Sofosbuvir (NS5B inhibitor)

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 .

GENERAL Back to hepacivirus page

Host

NATURAL HOSTS Human.
TROPISM Hepatocytes.
INTERACTIONS Cell receptors:
HCV: Heparan sulfate, LDL-R, CD81, CLDN1.
ASSOCIATED DISEASES Hepatitis.
hepatocellular carcinoma
TRANSMISSION Sexual contact, blood.

Matching UniProtKB/Swiss-Prot entries

(all links/actions below point to uniprot.org website)

35 entries grouped by strain

2 entries

Hepatitis C virus genotype 1a (isolate H77) (HCV) reference strain

Select_allDeselect_all
F_HCV77 F protein (Alternate reading frame protein/F-protein) (ARFP/F) (Frameshifted protein) (p16) (p17)
POLG_HCV77 Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 1A1R; 1A1V; 1CWX; 1HEI; 1JR6; 1N1L; 1ONB; 1R7C; 1R7D; 1R7E; 1R7F; 1R7G; 1RGQ; 2A4R; 2F9V; 2HD0; 2JXF; 2KDR; 2N1P; 2O8M; 2OBO; 2OBQ; 2OC0; 2OC1; 2OC7; 2OC8; 2OIN; 2P59; 2QV1; 2XI2; 2XI3; 2XNI; 3RC4; 3RC5; 4CL1; 4JZN; 4JZO; 4MWF; 4N0Y; 4Q0X; 4XVJ; 4Z0X; 5EOC; 5ERW; 5FGB; 5FGC; 5JZI; 5YXN; 5YXU; 6BQJ; 6BQK; 6BZU; 6BZV; 6BZW; 6BZY; 6UYD; 6WO5; 6WOQ; 7DUU

2 entries

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

Select_allDeselect_all
POLG_HCV1 Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 1RTL; 2A4G; 2GVF; 3EYD; 3HKW; 3KN2; 3QGH; 3QGI; 3RC4; 3RC5; 3SU4; 6MVO; 6N4N; 6VDO; 7MM3; 7MM4; 7MM9; 7MMA; 7MMB; 7MMC; 7MMD; 7MME; 7MMK; 7MML

F_HCV1 F protein (Alternate reading frame protein/F-protein) (ARFP/F) (Frameshifted protein) (p16) (p17)

1 entry

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

POLG_HCVBK Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 1A1Q; 1BT7; 1C2P; 1CSJ; 1CU1; 1GX5; 1GX6; 1JXP; 1NHU; 1NHV; 1NS3; 1OS5; 1QUV; 2AWZ; 2AX0; 2AX1; 2BRK; 2BRL; 2DXS; 2GIQ; 2GIR; 2HAI; 2HWH; 2HWI; 2I1R; 2JC0; 2JC1; 2O5D; 2WCX; 2WHO; 2WRM; 2XWY; 2ZKU; 3BR9; 3BSA; 3BSC; 3CDE; 3CIZ; 3CJ0; 3CJ2; 3CJ3; 3CJ4; 3CJ5; 3CO9; 3CVK; 3CWJ; 3D28; 3D5M; 3E51; 3FQK; 3FRZ; 3G86; 3GYN; 3H2L; 3H59; 3H5S; 3H5U; 3H98; 3IGV; 3MF5; 3RVB; 3UA7; 3UDL; 3VQS; 4A92; 4B6E; 4B6F; 4B71; 4B73; 4B74; 4B75; 4B76; 4DGV; 4DGY; 4EO6; 4EO8; 4IH5; 4IH6; 4IH7; 4K8B; 4KAI; 4KB7; 4KBI; 4KE5; 4MIA; 4MIB; 4MK7; 4MK8; 4MK9; 4MKA; 4MKB; 4TN2; 4WXP; 5FPS; 5FPT; 5FPY; 5KZP; 5W2E; 6MVP; 6W4G; 8OHM

1 entry

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

POLG_HCVCO Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 1ZH1; 2JY0; 2KWT; 2KWZ; 3FQL; 3FQM; 3FQQ; 3KN2; 3KQH; 3KQK; 3KQL; 3KQN; 3KQU; 3Q0Z; 3QGD; 3QGE; 3QGF; 3QGG; 4NLD; 4U01; 5E4F; 5PZK; 5PZL; 5PZM; 5PZN; 5PZO; 5PZP; 5TRH; 5TRI; 5TRJ; 5TRK; 5TWN

1 entry

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

POLG_HCVJ1 Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 2KNU; 3MRG; 3MRH; 3MRI; 3MRJ; 3MRL

1 entry

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

POLG_HCVJT Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVR6 Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVJA Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 1DXP; 1DY8; 1DY9; 1W3C; 2K8J; 3OYP; 3P8N; 3P8O; 4A1T; 4A1V; 4A1X; 4I31; 4I32; 4I33; 4JMY; 4KTC

1 entry

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

POLG_HCVTW Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 1N64; 2ZJO

1 entry

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

POLG_HCVJ4 Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 1NB4; 1NB6; 1NB7; 2F55; 2MTS; 2XHU; 2XHV; 2XHW; 2YOJ; 3CSO; 3GNV; 3GNW; 3GOL; 3HKY; 3LKH; 3MWV; 3MWW; 3SKA; 3SKE; 3SKH; 3TYQ; 3TYV; 3U4O; 3U4R; 3UPH; 3UPI; 4DRU; 4EAW; 4GMC; 4IZ0; 4J02; 4J04; 4J06; 4J08; 4J0A; 4JJS; 4JJU; 4JTW; 4JTY; 4JTZ; 4JU1; 4JU2; 4JU3; 4JU4; 4JU6; 4JU7; 4JVQ; 4JY0; 4JY1; 4MZ4; 4OOW; 4RY4; 4RY5; 4RY6; 4RY7; 5CZB; 5NPH; 5NPI

1 entry

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

POLG_HCVH9 Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVIN Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVJ6 Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 1YUY; 1YV2; 1YVX; 1YVZ; 2XWH; 4ADP

1 entry

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

POLG_HCVJF Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 2KZQ; 2LIF; 2LVG; 2XXD; 2XYM; 3I5K; 4AEP; 4AEX; 4E76; 4E78; 4E7A; 4J1V; 4OBC; 4WT9; 4WTA; 4WTC; 4WTD; 4WTE; 4WTF; 4WTG; 4WTI; 4WTJ; 4WTK; 4WTL; 4WTM; 5NPJ; 5QJ0; 5QJ1; 5TWM; 5UJ2; 6HT4

1 entry

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

POLG_HCVJ8 Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 1XCQ; 1XCT; 1XF5; 3GSZ; 3HVO

1 entry

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

POLG_HCVJP Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVBB Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVVA Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVNZ Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 6P6S

1 entry

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

POLG_HCVK3 Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVTR Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVJK Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVED Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 6P6Z

1 entry

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

POLG_HCVEV Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

pdb 2M6X

1 entry

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

POLG_HCVSA Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCV6A Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVEU Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVT5 Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVVN Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVJL Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVVP Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

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

POLG_HCVVO Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core ...

1 entry

Hepatitis GB virus B (GBV-B) (GB virus B)

POLG_GBVB Genome polyprotein [Cleaved into: Core protein; Envelope glycoprotein E1; Envelope glycoprotein E2 ...

pdb 2LZP; 2LZQ; 2MKB