Orthoflavivirus (taxid:3044782)
VIRION
Enveloped, spherical, about 50 nm in diameter. The surface proteins are arranged in an icosahedral-like symmetry. Mature virions contain two virus-encoded membrane proteins (M and E), while immature virions contain a membrane protein precursor.
Source: Zhang et al("Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/14528291)
GENOME
Monopartite, linear, ssRNA(+) genome of of 10-11 kb. The genome 5' end has a methylated nucleotide cap for canonical cellular translation. The 3' terminus is not polyadenylated but forms a loop structure. This secondary structure leads to the formation of a subgenomic flavivirus RNA (sfRNA) through genomic RNA degradation by host XRN1. sfRNA is essential for pathogenicity
, and may play a role in inhibiting host RIG-I antiviral activity as shown for Dengue virus
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
- RNA-dependent RNA polymerase [NS5]
- Cell-type capping
- Polyprotein major protease (Peptidase S7) [NS3]
REPLICATION
- Attachement of the viral envelope protein E to host receptors mediates internalization into the host cell by clathrin-mediated endocytosis, or by apoptotic mimicry
- Fusion of virus membrane with host endosomal membrane. RNA genome is released into the cytoplasm.
- 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).
- Replication takes place at the surface of endoplasmic reticulum in cytoplasmic viral factories. A dsRNA genome is synthesized from the genomic ssRNA(+).
- The dsRNA genome is transcribed/replicated thereby providing viral mRNAs/new ssRNA(+) genomes.
- Virus assembly occurs at the endoplasmic reticulum. The virion buds at the endoplasmic reticulum and is transported to the Golgi apparatus.
- The prM protein is cleaved in the Golgi, thereby maturing the virion which is fusion competent.
- Release of new virions by exocytosis.
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
.
Innate immune response inhibition
Dengue virus blocks STAT2 .
Matching UniProtKB/Swiss-Prot entries
(all links/actions below point to uniprot.org website)68 entries grouped by protein
2 entries
uORF1 protein
2 entries
uORF2 protein
59 entries
Genome polyprotein
4 entries
Structural polyprotein
1 entry