Members of the family Flaviviridae have monopartite, linear, single-stranded RNAgenomes of positive polarity, and 9.6 to 12.3 kilobase in total length. The 5'-termini of flaviviruses carry a methylatednucleotide cap, while other members of this family are uncapped and encode an internal ribosome entry site.
The genome encodes a single polyprotein with multiple transmembrane domains that is cleaved, by both host and viral proteases, into structural and non-structural proteins. Among the non-structural protein products (NS), the locations and sequences of NS3 and NS5, which contain motifs essential for polyprotein processing and RNA replication respectively, are relatively well conserved across the family and may be useful for phylogenetic analysis.
Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the viral envelope protein E to host receptors, which mediates clathrin-mediated endocytosis. Replication follows the positive-stranded RNA virus replication model. Positive-stranded RNA virus transcription is the method of transcription. Translation takes place by viral initiation. The virion assembles by budding through intracellular membranes and exits the host cell by exocytosis.[2][4][5]
A wide variety of natural hosts are used by different members of the Flaviviridae, including fish, mammals including humans and various invertebrates, such as those specific to mollusks and crustaceans.[6] The genomes of these flaviviruses show close synteny with that of the flavivirus type species, yellow fever virus.[7] One flavivirus, the Wenzhou shark flavivirus, infects both Pacific spadenose sharks (Scoliodon macrorhynchos) and Gazami crabs (Portunus trituberculatus) with overlapping ranges, raising the possibility of a two-host marine lifecycle.[6] However, another clade of flavivirus, the insect-specific flaviviruses, have genomes that do not demonstrate strong synteny with any of these groups, suggesting a complex evolutionary history.[2][8]
Flavivirus endogenous viral elements, traces of flavivirus genomes integrated into the host's DNA, are found in many species, including a tadpole shrimp Lepidurus articus, the water flea Daphnia magna and a freshwater jellyfish Craspedacusta sowerbii,[7] suggesting ancient coevolution between animal and flavivirus lineages.[6][7] Many of the well-known members of the family causing disease in vertebrates are transmitted via arthropod vectors (ticks and mosquitoes).[2][4][7]
Taxonomy
Phylogenetic tree of Flaviviridae using the NS3 protein sequences
The Flaviviridae are part of RNA virus supergroup II, which includes certain plant viruses and bacterial viruses.[2]
Other Orthoflaviviruses are known that have yet to be classified. These include Wenling shark virus.
Jingmenvirus is a group of unclassified viruses in the family which includes Alongshan virus, Guaico Culex virus, Jingmen tick virus and Mogiana tick virus. These viruses have a segmented genome of four or five pieces. Two of these segments are derived from flaviviruses.[citation needed]
A number of viruses may be related to the flaviviruses, but have features that are atypical of the flaviviruses. These include citrus Jingmen-like virus, soybean cyst nematode virus 5, Toxocara canis larva agent, Wuhan cricket virus, and possibly Gentian Kobu-sho-associated virus.[citation needed]
Clinical importance
Major diseases caused by members of the family Flaviviridae include:
