Editing Flaviviridae

{{Short description|Family of viruses}}
{{Virusbox
| image = Viruses-10-00597-g001.png
| image_alt = 
| image_caption = [[Zika virus]] virion structure and genome
| taxon              = Flaviviridae
| subdivision_ranks  = Genera
| subdivision        =
* ''[[Flavivirus]]''
* ''[[Hepacivirus]]''
* ''[[Pegivirus]]''
* ''[[Pestivirus]]''
}}

'''''Flaviviridae''''' is a family of [[Viral envelope|enveloped]] [[positive-strand RNA virus]]es which mainly infect [[mammal]]s and [[bird]]s.<ref name=ICTVProfile>{{cite journal|last1=Simmonds|first1=P|last2=Becher|first2=P|last3=Bukh|first3=J|last4=Gould|first4=E|last5=Meyers|first5=G|last6=Monath|first6=T|last7=Muerhoff|first7=S|last8=Pletnev|first8=A|last9=Rico-Hesse|first9=R|last10=Smith|first10=D|last11=Stapleton|first11=J|last12=ICTV Report Consortium|title=ICTV Virus Taxonomy Profile: Flaviviridae|journal=Journal of General Virology|date=2017|volume=98|issue=1|pages=2–3|doi=10.1099/jgv.0.000672|pmid=28218572|pmc=5370391}}</ref> They are primarily spread through [[arthropod]] [[vector (epidemiology)|vectors]] (mainly [[tick]]s and [[mosquito]]es).<ref name="ICTVReport" /> The family gets its name from the [[yellow fever]] virus; ''flavus'' is Latin for "yellow", and yellow fever in turn was named because of its propensity to cause [[jaundice]] in victims.<ref>{{cite web|title=Flaviviridae|url=http://microbewiki.kenyon.edu/index.php/Flaviviridae|publisher=Microbe Wiki|access-date=July 22, 2008}}</ref> There are 89 species in the family divided among four genera.<ref name="ICTVReport">{{cite web|url=http://www.ictv.global/report/flaviviridae|title=Flaviviridae|website=ICTV Online Report|language=en|access-date=11 July 2024|last=Ricco-Hesse|first=Rebecca|editor-last1=Knowles|editor-first1=Nick J.|editor-last2=Siddell|editor-first2=Stuart G.|year=2023}}</ref> Diseases associated with the group include: [[hepatitis]] ([[hepacivirus]]es), [[Bleeding|hemorrhagic syndromes]], [[Bovine viral diarrhea|fatal mucosal disease]] ([[pestivirus]]es), [[Viral hemorrhagic fever|hemorrhagic fever]], [[encephalitis]], and the birth defect [[microcephaly]] ([[flavivirus]]es).<ref name="ViralZone">{{cite web|title=Viral Zone|url=http://viralzone.expasy.org/all_by_species/43.html|access-date=11 July 2024|publisher=ExPASy}}</ref>

== Structure ==
Virus particles are enveloped and spherical with icosahedral-like geometries that have pseudo T=3 symmetry. They are about 40–60 [[nanometer|nm]] in diameter.<ref name="ICTVReport" /><ref name="ViralZone" />

==Genome==
{{inline citations needed|section|date=July 2024}}
Members of the family ''Flaviviridae'' have monopartite, linear, single-stranded [[RNA]] [[genomes]] of positive polarity, and 9.6 to 12.3 kilobase in total length. The 5'-termini of flaviviruses carry a [[methylation|methylated]] [[nucleotide]] 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.

== Life cycle ==
[[File:Pathogens-07-00068-g002.webp|thumb|Life cycle of [[Japanese encephalitis virus]] (JEV)]]
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.<ref name="ICTVReport" /><ref name="ViralZone" /><ref>{{cite journal|vauthors=Simmonds P, Becher P, Bukh J, Gould EA, Meyers G, Monath T, Muerhoff S, Pletnet A, Rico-Hesse R, Smith DB, Stapleton JT, ((ICTV Report Consortium))|title=ICTV Virus Taxonomy Profile: ''Flaviviridae''|journal=Journal of General Virology|year=2017|volume=98|issue=1|pages=2–3|doi=10.1099/jgv.0.000672|pmid=28218572|pmc=5370391|doi-access=free}}</ref>

{| class="wikitable sortable collapsible collapsed" style="text-align:center"
|-
! Genus !! Host details !! Tissue tropism !! Entry details !! Release details !! Replication site !! Assembly site !! Transmission
|-
|''Flavivirus''||Humans; mammals; mosquitoes; ticks||Epithelium: skin; epithelium: kidney; epithelium: intestine; epithelium: testes||Clathrin-mediated endocytosis||Secretion||Cytoplasm||Cytoplasm||Zoonosis; arthropod bite
|-
|''Hepacivirus''||Humans||Epithelium: skin; epithelium: kidney; epithelium: intestine; epithelium: testes||Clathrin-mediated endocytosis||Secretion||Cytoplasm||Cytoplasm||Sex; blood
|-
|''Pegivirus''||Mammals||None||Clathrin-mediated endocytosis||Secretion||Cytoplasm||Cytoplasm||Unknown
|-
|''Pestivirus''||Mammals||None||Clathrin-mediated endocytosis||Secretion||Cytoplasm||Cytoplasm||Vertical: parental
|}

==Host range and evolutionary history==
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.<ref name=lensink2022>{{cite journal|title=Aquatic Flaviviruses|vauthors=Lensink MJ, Li Y, Lequime S|journal=Journal of Virology|volume=96|issue=17|year=2022|pages=e0043922 |doi=10.1128/jvi.00439-22|pmid=35975997|pmc=9472621|id=Art. No. e00439-22}}</ref>  The genomes of these flaviviruses show close [[synteny]] with that of the flavivirus type species, yellow fever virus.<ref name=parryasgari2019>{{cite journal|vauthors=Parry R, Asgari S|title=Discovery of Novel Crustacean and Cephalopod Flaviviruses: Insights into the Evolution and Circulation of Flaviviruses between Marine Invertebrate and Vertebrate Hosts|journal=Journal of Virology|volume=93|issue=14|id=Art. No. e00432-19|year=2019|doi=10.1128/JVI.00432-19|pmid=31068424|pmc=6600200}}</ref>  One flavivirus, the [[Wenzhou shark flavivirus]], infects both [[Pacific spadenose shark]]s (''Scoliodon macrorhynchos'') and [[Gazami crab]]s (''Portunus trituberculatus'') with overlapping ranges, raising the possibility of a two-host marine lifecycle.<ref name=lensink2022/>  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.<ref name="ICTVReport"/><ref>{{cite journal|vauthors=Shi M, Lin XD, Vasilakis N, Tian JH, Li CX, Chen LJ, Eastwood G, Diao XN, Chen MH, Chen X, Qin XC, Widen SG, Wood TG, Tesh RB, Xu J, Holmes EC, Zhang YZ|display-authors=6|title=Divergent Viruses Discovered in Arthropods and Vertebrates Revise the Evolutionary History of the Flaviviridae and Related Viruses|journal=Journal of Virology|year=2015|volume=90|issue=2|pages=659–669|doi=10.1128/JVI.02036-15|pmid=26491167|pmc=4702705}}</ref>

Flavivirus [[endogenous viral element]]s, 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]]'',<ref name=parryasgari2019/> suggesting ancient coevolution between animal and flavivirus lineages.<ref name=lensink2022/><ref name=parryasgari2019/>   Many of the well-known members of the family causing disease in vertebrates are transmitted via arthropod vectors (ticks and mosquitoes).<ref name="ICTVReport" /><ref name="ViralZone" /><ref name=parryasgari2019/>

== Taxonomy ==
[[File:Doi.org-10.7717-peerj.74-Fig-1-full.png|thumb|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.<ref name="ICTVReport" />

The family has four genera:<ref name="ICTVProfile" /><ref name="ICTVReport" />
*Genus ''[[Flavivirus]],'' renamed ''Orthoflavivirus'' in 2023, (includes [[Dengue virus]], [[Japanese encephalitis virus]], [[Kyasanur Forest disease virus]], [[Powassan virus]], [[West Nile virus]], [[Yellow fever virus]], and [[Zika virus]])
*Genus ''[[Hepacivirus]]'' (includes [[hepatitis C virus]] and GB virus B)
*Genus ''[[Pegivirus]]'' (includes GB virus A, GB virus C, and GB virus D))
*Genus ''[[Pestivirus]]'' (includes [[bovine viral diarrhea virus|bovine viral diarrhea virus 1]]) and [[classical swine fever virus]], previously hog cholera virus)). Viruses in this genus infect nonhuman mammals.

;Unclassified

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|date=July 2024}}

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|date=July 2024}}

==Clinical importance==
Major diseases caused by members of the family ''Flaviviridae'' include:
{{Columns-list|colwidth=15em|
* [[Dengue fever]]
* [[Hepatitis C]] 
* [[Japanese encephalitis]]
* [[Kyasanur Forest disease]]
* [[Murray Valley encephalitis]]
* [[St. Louis encephalitis]]
* [[Tick-borne encephalitis]]
* [[West Nile encephalitis]]
* [[Yellow fever]]
* [[Zika fever]]
}}

==References==
{{Reflist}}

==External links==
* [http://www.ictv.global/report/flaviviridae '''ICTV Report''': ''Flaviviridae'']
* [https://web.archive.org/web/20151208033835/http://www.vbrc.org/query.asp?web_taxonomy=Flaviviridae Flaviviridae Genomes] database search results from the [http://www.vbrc.org Viral Bioinformatics Resource Center]
* [http://viralzone.expasy.org/all_by_species/43.html '''Viralzone''': Flaviviridae]
* [http://www.viprbrc.org/brc/home.do?decorator=flavi Virus Pathogen Database and Analysis Resource (ViPR): Flaviviridae]
* {{cite web |title=''Flaviviridae'' |work=NCBI Taxonomy Browser |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11050 |id=11050}}

{{Baltimore classification}}
{{Zoonotic viral diseases}}
{{Taxonbar|from=Q1331256}}
{{Authority control}}

[[Category:Flaviviridae| ]]
[[Category:Virus families]]
[[Category:Riboviria]]