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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.

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 .

https://www.ncbi.nlm.nih.gov/nuccore/
IsolateID Species ICTV_ID Exemplar or Additional Virus name Acronym Isolate Genome coverage host GenBankAC UniProtAC
VMR1009042 Hepacivirus bovis ICTV20165295 E bovine hepacivirus BoHV GER/2014 Coding-complete genome vertebrates KP641127 A0A0F7JH93
VMR1009043 Hepacivirus colobi ICTV20165285 E guereza hepacivirus GHV 1/BWC08 Coding-complete genome vertebrates KC551800 S5E367
VMR1009044 Hepacivirus equi ICTV20165283 E non-primate hepacivirus NPHV NZP1 Complete genome vertebrates KP325401 A0A0B5HK21
VMR1009045 Hepacivirus glareoli ICTV20165291 E rodent hepacivirus RHV-J 3382/GER/2010 Coding-complete genome vertebrates KC411777 R9QTE4
VMR1009046 Hepacivirus hominis ICTV19910774 E hepatitis C virus genotype 1a HCV1a H77 Complete genome vertebrates AF009606 P27958
VMR1012771 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 1a HCV1a PT Complete genome vertebrates M62321 P26664
VMR1012772 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 1b HCV1b J Coding-complete genome vertebrates D90208 P26662
VMR1012773 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 2a HCV2a HC-J6 Coding-complete genome vertebrates D00944 P26660
VMR1012774 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 2b HCV2b HC-J8 Coding-complete genome vertebrates D10988 P26661
VMR1012775 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 3a HCV3a NZL1 Coding-complete genome vertebrates D17763 Q81258
VMR1012776 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 3k HCV3k JK049 Coding-complete genome vertebrates D63821 Q68801
VMR1012777 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 4a HCV4a ED43 Coding-complete genome vertebrates GU814265 D6P446
VMR1012778 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 5a HCV5a EUH1480 Coding-complete genome vertebrates Y13184 O39928
VMR1012779 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 6a HCV6a euhk2 Coding-complete genome vertebrates Y12083 O39927
VMR1012780 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 6g HCV6g JK046 Coding-complete genome vertebrates D63822 Q68798
VMR1012781 Hepacivirus hominis ICTV19910774 A hepatitis C virus genotype 7a HCV7a QC69 Coding-complete genome vertebrates EF108306 A8QPD9
VMR1009047 Hepacivirus macronycteridis ICTV20165292 E bat hepacivirus BHV-K PDB-829 Coding-complete genome vertebrates KC796074 M9ZZL8
VMR1009048 Hepacivirus myodae ICTV20165287 E rodent hepacivirus RHV-F 25842 Coding-complete genome vertebrates KC411784 R9QTQ6
VMR1009049 Hepacivirus norvegici ICTV20165289 E Norway rat hepacivirus 2 NRHV2 E43 Complete genome vertebrates KJ950939 A0A097NZB6
VMR1009050 Hepacivirus otomopis ICTV20165294 E bat hepacivirus BHV-M PDB-491.1 Coding-complete genome vertebrates KC796078 N0A109
VMR1009051 Hepacivirus peromysci ICTV20165286 E rodent hepacivirus RHV-E 339 Complete genome vertebrates KC815310 M9UVS3
VMR1009052 Hepacivirus platyrrhini ICTV20165284 E GB virus-B GBV-B B Complete genome vertebrates U22304 Q69422
VMR1009053 Hepacivirus ratti ICTV20165288 E Norway rat hepacivirus 1 NRHV1 C12 Coding-complete genome vertebrates KJ950938 A0A097NZA3
VMR1012782 Hepacivirus ratti ICTV20165288 A Norway rat hepacivirus 1 NRHV1 rn-1 Complete genome vertebrates KX905133 A0A247ZNN0
VMR1009054 Hepacivirus rhabdomysis ICTV20165290 E rodent hepacivirus RHV-I 3/RSA/2008 Coding-complete genome vertebrates KC411806 R9QT72
VMR1009055 Hepacivirus vittatae ICTV20165293 E bat hepacivirus BHV-L PDB-112 Coding-complete genome vertebrates KC796077 M9ZRW5

Matching UniProtKB/Swiss-Prot entries

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

35 entries grouped by protein

2 entries

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

Select_allDeselect_all
F_HCV77
Hepatitis C virus genotype 1a (isolate H77) (HCV) reference strain
F_HCV1
Hepatitis C virus genotype 1a (isolate 1) (HCV)

33 entries

Genome polyprotein

Select_allDeselect_all
POLG_HCV77
Hepatitis C virus genotype 1a (isolate H77) (HCV) reference strain
POLG_GBVB
Hepatitis GB virus B (GBV-B) (GB virus B)
POLG_HCV1
Hepatitis C virus genotype 1a (isolate 1) (HCV)
POLG_HCV6A
Hepatitis C virus genotype 6a (isolate 6a33) (HCV)
POLG_HCVBB
Hepatitis C virus genotype 2c (isolate BEBE1) (HCV)
POLG_HCVCO
Hepatitis C virus genotype 1b (isolate Con1) (HCV)
POLG_HCVED
Hepatitis C virus genotype 4a (isolate ED43) (HCV)
POLG_HCVEU
Hepatitis C virus genotype 6a (isolate EUHK2) (HCV)
POLG_HCVEV
Hepatitis C virus genotype 5a (isolate EUH1480) (HCV)
POLG_HCVH9
Hepatitis C virus genotype 1c (isolate HC-G9) (HCV)
POLG_HCVIN
Hepatitis C virus genotype 1c (isolate India) (HCV)
POLG_HCVJ1
Hepatitis C virus genotype 1b (isolate HC-J1) (HCV)
POLG_HCVJ4
Hepatitis C virus genotype 1b (strain HC-J4) (HCV)
POLG_HCVJ6
Hepatitis C virus genotype 2a (isolate HC-J6) (HCV)
POLG_HCVJ8
Hepatitis C virus genotype 2b (isolate HC-J8) (HCV)
POLG_HCVJA
Hepatitis C virus genotype 1b (isolate Japanese) (HCV)
POLG_HCVJF
Hepatitis C virus genotype 2a (isolate JFH-1) (HCV)
POLG_HCVJK
Hepatitis C virus genotype 3k (isolate JK049) (HCV)
POLG_HCVJL
Hepatitis C virus genotype 6g (isolate JK046) (HCV)
POLG_HCVJP
Hepatitis C virus genotype 2b (isolate JPUT971017) (HCV)
POLG_HCVJT
Hepatitis C virus genotype 1b (isolate HC-JT) (HCV)
POLG_HCVK3
Hepatitis C virus genotype 3a (isolate k3a) (HCV)
POLG_HCVNZ
Hepatitis C virus genotype 3a (isolate NZL1) (HCV)
POLG_HCVR6
Hepatitis C virus genotype 1b (isolate HCR6) (HCV)
POLG_HCVSA
Hepatitis C virus genotype 5a (isolate SA13) (HCV)
POLG_HCVT5
Hepatitis C virus genotype 6b (isolate Th580) (HCV)
POLG_HCVTR
Hepatitis C virus genotype 3b (isolate Tr-Kj) (HCV)
POLG_HCVTW
Hepatitis C virus genotype 1b (isolate Taiwan) (HCV)
POLG_HCVVA
Hepatitis C virus genotype 2k (isolate VAT96) (HCV)
POLG_HCVVN
Hepatitis C virus genotype 6d (isolate VN235) (HCV)
POLG_HCVVO
Hepatitis C virus genotype 6k (isolate VN405) (HCV)
POLG_HCVVP
Hepatitis C virus genotype 6h (isolate VN004) (HCV)