Flaviviridae

VIRION

Enveloped, spherical, about 50 nm in diameter. The surface proteins are arranged in an icosahedral-like symmetry.
Source: Zhang et al

GENOME

Monopartite, linear, ssRNA(+) genome of about 9.7-12 kb. The genome 3’ terminus is not polyadenylated but forms a loop structure. The 5’ end has a methylated nucleotide cap (to allow translation) or a genome-linked protein (VPg).

GENE EXPRESSION

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

REPLICATION

CYTOPLASMIC

  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(+).
  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

Adaptive immune response inhibition

Dengue NS1 protein inhibits host complement by binding C4 and reducing C4b deposition and C3 convertase activity. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. .

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 , whilst Dengue virus blocks STAT2
Hepatitis C virus inhibits the host IFN-mediated response by blocking host MAVS , TRAFs and TBK1-IKBKE-DDX3 complex , whilst pestiviruses N(pro) blocks host IRF-3 .

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

82 entries grouped by protein

All proteins are shown (view only 81 complete proteome entries)

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

Select_all Deselect_all  
F_HCVHHepatitis C virus genotype 1a (isolate H) (HCV) reference strain
F_HCV1Hepatitis C virus genotype 1a (isolate 1) (HCV)

Genome polyprotein

Select_all Deselect_all  
POLG_BVDVNBovine viral diarrhea virus (isolate NADL) (BVDV) (Mucosal disease virus) reference strain
POLG_DEN1WDengue virus type 1 (strain Nauru/West Pac/1974) (DENV-1) reference strain
POLG_HCVHHepatitis C virus genotype 1a (isolate H) (HCV) reference strain
POLG_YEFV1Yellow fever virus (strain 17D vaccine) (YFV) reference strain
POLG_BVDVCBovine viral diarrhea virus (strain CP7) (BVDV) (Mucosal disease virus)
POLG_BVDVSBovine viral diarrhea virus (strain SD-1) (BVDV) (Mucosal disease virus)
POLG_CSFVAClassical swine fever virus (strain Alfort) (CSFV) (Hog cholera virus)
POLG_CSFVBClassical swine fever virus (strain Brescia) (CSFV) (Hog cholera virus)
POLG_DEN1BDengue virus type 1 (strain Brazil/97-11/1997) (DENV-1)
POLG_DEN1SDengue virus type 1 (strain Singapore/S275/1990) (DENV-1)
POLG_DEN28Dengue virus type 2 (isolate Thailand/0168/1979) (DENV-2)
POLG_DEN27Dengue virus type 2 (strain 16681-PDK53) (DENV-2)
POLG_DEN2JDengue virus type 2 (strain Jamaica/1409/1983) (DENV-2)
POLG_DEN2QDengue virus type 2 (strain Peru/IQT2913/1996) (DENV-2)
POLG_DEN2PDengue virus type 2 (strain Puerto Rico/PR159-S1/1969) (DENV-2)
POLG_DEN26Dengue virus type 2 (strain Thailand/16681/1984) (DENV-2)
POLG_DEN2NDengue virus type 2 (strain Thailand/NGS-C/1944) (DENV-2)
POLG_DEN3CDengue virus type 3 (strain China/80-2/1980) (DENV-3)
POLG_DEN3MDengue virus type 3 (strain Martinique/1243/1999) (DENV-3)
POLG_DEN3PDengue virus type 3 (strain Philippines/H87/1956) (DENV-3)
POLG_DEN3IDengue virus type 3 (strain Singapore/8120/1995) (DENV-3)
POLG_DEN3SDengue virus type 3 (strain Sri Lanka/1266/2000) (DENV-3)
POLG_DEN4DDengue virus type 4 (strain Dominica/814669/1981) (DENV-4)
POLG_DEN4PDengue virus type 4 (strain Philippines/H241/1956) (DENV-4)
POLG_DEN4SDengue virus type 4 (strain Singapore/8976/1995) (DENV-4)
POLG_DEN4TDengue virus type 4 (strain Thailand/0348/1991) (DENV-4)
POLG_DEN4HDengue virus type 4 (strain Thailand/0476/1997) (DENV-4)
POLG_HCV1Hepatitis C virus genotype 1a (isolate 1) (HCV)
POLG_HCVBKHepatitis C virus genotype 1b (isolate BK) (HCV)
POLG_HCVCOHepatitis C virus genotype 1b (isolate Con1) (HCV)
POLG_HCVJ1Hepatitis C virus genotype 1b (isolate HC-J1) (HCV)
POLG_HCVJTHepatitis C virus genotype 1b (isolate HC-JT) (HCV)
POLG_HCVR6Hepatitis C virus genotype 1b (isolate HCR6) (HCV)
POLG_HCVJAHepatitis C virus genotype 1b (isolate Japanese) (HCV)
POLG_HCVTWHepatitis C virus genotype 1b (isolate Taiwan) (HCV)
POLG_HCVJ4Hepatitis C virus genotype 1b (strain HC-J4) (HCV)
POLG_HCVH9Hepatitis C virus genotype 1c (isolate HC-G9) (HCV)
POLG_HCVINHepatitis C virus genotype 1c (isolate India) (HCV)
POLG_HCVJ6Hepatitis C virus genotype 2a (isolate HC-J6) (HCV)
POLG_HCVJFHepatitis C virus genotype 2a (isolate JFH-1) (HCV)
POLG_HCVJ8Hepatitis C virus genotype 2b (isolate HC-J8) (HCV)
POLG_HCVJPHepatitis C virus genotype 2b (isolate JPUT971017) (HCV)
POLG_HCVBBHepatitis C virus genotype 2c (isolate BEBE1) (HCV)
POLG_HCVVAHepatitis C virus genotype 2k (isolate VAT96) (HCV)
POLG_HCVK3Hepatitis C virus genotype 3a (isolate k3a) (HCV)
POLG_HCVNZHepatitis C virus genotype 3a (isolate NZL1) (HCV)
POLG_HCVTRHepatitis C virus genotype 3b (isolate Tr-Kj) (HCV)
POLG_HCVJKHepatitis C virus genotype 3k (isolate JK049) (HCV)
POLG_HCVEDHepatitis C virus genotype 4a (isolate ED43) (HCV)
POLG_HCVEVHepatitis C virus genotype 5a (isolate EUH1480) (HCV)
POLG_HCVSAHepatitis C virus genotype 5a (isolate SA13) (HCV)
POLG_HCV6AHepatitis C virus genotype 6a (isolate 6a33) (HCV)
POLG_HCVEUHepatitis C virus genotype 6a (isolate EUHK2) (HCV)
POLG_HCVT5Hepatitis C virus genotype 6b (isolate Th580) (HCV)
POLG_HCVVNHepatitis C virus genotype 6d (isolate VN235) (HCV)
POLG_HCVJLHepatitis C virus genotype 6g (isolate JK046) (HCV)
POLG_HCVVPHepatitis C virus genotype 6h (isolate VN004) (HCV)
POLG_HCVVOHepatitis C virus genotype 6k (isolate VN405) (HCV)
POLG_GBVBHepatitis GB virus B (GBV-B) (GB virus B)
POLG_JAEVJJapanese encephalitis virus (strain Jaoars982)
POLG_JAEV5Japanese encephalitis virus (strain SA(v))
POLG_JAEV1Japanese encephalitis virus (strain SA-14)
POLG_KUNJMKunjin virus (strain MRM61C)
POLG_LANVTLangat virus (strain TP21)
POLG_LIVLouping ill virus (Li)
POLG_MCFAMosquito cell fusing agent (CFA flavivirus)
POLG_MVEV5Murray valley encephalitis virus (strain MVE-1-51) (MVEV)
POLG_TBEVHTick-borne encephalitis virus (strain Hypr) (TBEV)
POLG_TBEVWTick-borne encephalitis virus European subtype (strain Neudoerfl) (NEUV) ...
POLG_TBEVSTick-borne encephalitis virus Far Eastern subtype (strain Sofjin) (SOFV) ...
POLG_POWVLTick-borne powassan virus (strain LB) (POWV) (Powassan virus)
POLG_WNVWest Nile virus (WNV)
POLG_YEFVNYellow fever virus (isolate Angola/14FA/1971) (YFV)
POLG_YEFVEYellow fever virus (isolate Ethiopia/Couma/1961) (YFV)
POLG_YEFVCYellow fever virus (isolate Ivory Coast/1999) (YFV)
POLG_YEFVIYellow fever virus (isolate Ivory Coast/85-82H/1982) (YFV)
POLG_YEFVUYellow fever virus (isolate Uganda/A7094A4/1948) (YFV)
POLG_YEFVFYellow fever virus (strain French neurotropic vaccine FNV) (YFV)
POLG_YEFVAYellow fever virus (strain Ghana/Asibi/1927) (YFV)
POLG_YEFVTYellow fever virus (strain Trinidad/TRINID79A/1979) (YFV)