Flavivirus

Flavivirus
	A TEM micrograph of Yellow fever virus
	Zika virus viral envelope model, colored by chains, PDB entry 5ire
Virus classification
(unranked):	Virus
Realm:	Riboviria
Kingdom:	Orthornavirae
Phylum:	Kitrinoviricota
Class:	Flasuviricetes
Order:	Amarillovirales
Family:	Flaviviridae
Genus:	Flavivirus
Species
	See text

Flavivirus, renamed Orthoflavivirus in 2023,^[3] is a genus of positive-strand RNA viruses in the family Flaviviridae. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and several other viruses which may cause encephalitis,^[4] as well as insect-specific flaviviruses (ISFs) such as cell fusing agent virus (CFAV), Palm Creek virus (PCV), and Parramatta River virus (PaRV).^[5] While dual-host flaviviruses can infect vertebrates as well as arthropods, insect-specific flaviviruses are restricted to their competent arthropods.^[6] The means by which flaviviruses establish persistent infection in their competent vectors and cause disease in humans depends upon several virus-host interactions, including the intricate interplay between flavivirus-encoded immune antagonists and the host antiviral innate immune effector molecules.^[7]

Flaviviruses are named for the yellow fever virus; the word flavus means 'yellow' in Latin, and yellow fever in turn is named from its propensity to cause yellow jaundice in victims.^[8]

Flaviviruses share several common aspects: common size (40–65 nm), symmetry (enveloped, icosahedral nucleocapsid), nucleic acid (positive-sense, single-stranded RNA around 10,000–11,000 bases), and appearance under the electron microscope.^{[citation needed]}

Most of these viruses are primarily transmitted by the bite from an infected arthropod (mosquito or tick), and hence are classified as arboviruses. Human infections with most of these arboviruses are incidental, as humans are unable to replicate the virus to high enough titers to reinfect the arthropods needed to continue the virus life-cycle – humans are then a dead end host. The exceptions to this are the yellow fever virus, dengue virus and zika virus. These three viruses still require mosquito vectors but are well-enough adapted to humans as to not necessarily depend upon animal hosts (although they continue to have important animal transmission routes, as well).

Other virus transmission routes for arboviruses include handling infected animal carcasses, blood transfusion, sex, childbirth and consumption of unpasteurised milk products. Transmission from nonhuman vertebrates to humans without an intermediate vector arthropod however mostly occurs with low probability. For example, early tests with yellow fever showed that the disease is not contagious.

The known non-arboviruses of the flavivirus family reproduce in either arthropods or vertebrates, but not both, with one odd member of the genus affecting a nematode.^[9]

^ "Virus Taxonomy: 2018b Release". International Committee on Taxonomy of Viruses (ICTV). March 2019. Retrieved 16 March 2019.
^ Sirohi D, Chen Z, Sun L, Klose T, Pierson TC, Rossmann MG, Kuhn RJ (April 2016). "The 3.8 Å resolution cryo-EM structure of Zika virus". Science. 352 (6284): 467–470. Bibcode:2016Sci...352..467S. doi:10.1126/science.aaf5316. PMC 4845755. PMID 27033547.
^ Postler TS, Beer M, Blitvich BJ, Bukh J, de Lamballerie X, Drexler JF, Imrie A, Kapoor A, Karganova GG, Lemey P, Lohmann V, Simmonds P, Smith DB, Stapleton JT, Kuhn JH (10 August 2023). "Renaming of the genus Flavivirus to Orthoflavivirus and extension of binomial species names within the family Flaviviridae". Archives of Virology. 168 (9): 224. doi:10.1007/s00705-023-05835-1. ISSN 1432-8798. PMID 37561168.
^ Shi, P-Y, ed. (2012). Molecular Virology and Control of Flaviviruses. Caister Academic Press. ISBN 978-1-904455-92-9.
^ McLean BJ, Hobson-Peters J, Webb CE, Watterson D, Prow NA, Nguyen HD, Hall-Mendelin S, Warrilow D, Johansen CA, Jansen CC, van den Hurk AF, Beebe NW, Schnettler E, Barnard RT, Hall RA (2015). "A novel insect-specific flavivirus replicates only in Aedes-derived cells and persists at high prevalence in wild Aedes vigilax populations in Sydney, Australia". Virology. 486: 272–283. doi:10.1016/j.virol.2015.07.021. PMID 26519596.
^ Elrefaey AM, Abdelnabi R, Rosales Rosas AL, Wang L, Basu S, Delang L (September 2020). "Understanding the Mechanisms Underlying Host Restriction of Insect-Specific Viruses". Viruses. 12 (9): 964. doi:10.3390/v12090964. PMC 7552076. PMID 32878245.
^ Elrefaey AM, Hollinghurst P, Reitmayer CM, Alphey L, Maringer K (November 2021). "Innate Immune Antagonism of Mosquito-Borne Flaviviruses in Humans and Mosquitoes". Viruses. 13 (11): 2116. doi:10.3390/v13112116. PMC 8624719. PMID 34834923.
^
The earliest mention of "yellow fever" appears in a manuscript of 1744 by John Mitchell of Virginia; copies of the manuscript were sent to Mr. Cadwallader Colden, a physician in New York, and to Benjamin Rush of Philadelphia; the manuscript was eventually reprinted in 1814. See:
- Mitchell, John (written: 1744; reprinted: 1814) "Account of the Yellow fever which prevailed in Virginia in the years 1737, 1741, and 1742, in a letter to the late Cadwallader Colden, Esq. of New York, from the late John Mitchell, M.D.F.R.S. of Virginia", American Medical and Philosophical Register, 4: 181–215.
The term "yellow fever" appears on p. 186. On p. 188, Mitchell mentions "... the distemper was what is generally called the yellow fever in America." However, on pages 191–192, he states "... I shall consider the cause of the yellowness which is so remarkable in this distemper, as to have given it the name of the Yellow Fever." Mitchell misdiagnosed the disease that he observed and treated, and the disease was probably Weil's disease or hepatitis. See: Saul Jarcho (1957) "John Mitchell, Benjamin Rush, and Yellow fever". Bulletin of the History of Medicine, 31 (2): 132–6.
^ Bekal S, Domier LL, Gonfa B, McCoppin NK, Lambert KN, Bhalerao K (2014). "A novel flavivirus in the soybean cyst nematode". Journal of General Virology. 95 (Pt 6): 1272–1280. doi:10.1099/vir.0.060889-0. PMID 24643877.

[ictv-1] "Virus Taxonomy: 2018b Release". International Committee on Taxonomy of Viruses (ICTV). March 2019. Retrieved 16 March 2019.

[SirohiChen2016-2] Sirohi D, Chen Z, Sun L, Klose T, Pierson TC, Rossmann MG, Kuhn RJ (April 2016). "The 3.8 Å resolution cryo-EM structure of Zika virus". Science. 352 (6284): 467–470. Bibcode:2016Sci...352..467S. doi:10.1126/science.aaf5316. PMC 4845755. PMID 27033547.

[3] Postler TS, Beer M, Blitvich BJ, Bukh J, de Lamballerie X, Drexler JF, Imrie A, Kapoor A, Karganova GG, Lemey P, Lohmann V, Simmonds P, Smith DB, Stapleton JT, Kuhn JH (10 August 2023). "Renaming of the genus Flavivirus to Orthoflavivirus and extension of binomial species names within the family Flaviviridae". Archives of Virology. 168 (9): 224. doi:10.1007/s00705-023-05835-1. ISSN 1432-8798. PMID 37561168.

[ShiP-Y-4] Shi, P-Y, ed. (2012). Molecular Virology and Control of Flaviviruses. Caister Academic Press. ISBN 978-1-904455-92-9.

[mclean-5] McLean BJ, Hobson-Peters J, Webb CE, Watterson D, Prow NA, Nguyen HD, Hall-Mendelin S, Warrilow D, Johansen CA, Jansen CC, van den Hurk AF, Beebe NW, Schnettler E, Barnard RT, Hall RA (2015). "A novel insect-specific flavivirus replicates only in Aedes-derived cells and persists at high prevalence in wild Aedes vigilax populations in Sydney, Australia". Virology. 486: 272–283. doi:10.1016/j.virol.2015.07.021. PMID 26519596.

[6] Elrefaey AM, Abdelnabi R, Rosales Rosas AL, Wang L, Basu S, Delang L (September 2020). "Understanding the Mechanisms Underlying Host Restriction of Insect-Specific Viruses". Viruses. 12 (9): 964. doi:10.3390/v12090964. PMC 7552076. PMID 32878245.

[7] Elrefaey AM, Hollinghurst P, Reitmayer CM, Alphey L, Maringer K (November 2021). "Innate Immune Antagonism of Mosquito-Borne Flaviviruses in Humans and Mosquitoes". Viruses. 13 (11): 2116. doi:10.3390/v13112116. PMC 8624719. PMID 34834923.

[8] The earliest mention of "yellow fever" appears in a manuscript of 1744 by John Mitchell of Virginia; copies of the manuscript were sent to Mr. Cadwallader Colden, a physician in New York, and to Benjamin Rush of Philadelphia; the manuscript was eventually reprinted in 1814. See:
Mitchell, John (written: 1744; reprinted: 1814) "Account of the Yellow fever which prevailed in Virginia in the years 1737, 1741, and 1742, in a letter to the late Cadwallader Colden, Esq. of New York, from the late John Mitchell, M.D.F.R.S. of Virginia", American Medical and Philosophical Register, 4: 181–215.
The term "yellow fever" appears on p. 186. On p. 188, Mitchell mentions "... the distemper was what is generally called the yellow fever in America." However, on pages 191–192, he states "... I shall consider the cause of the yellowness which is so remarkable in this distemper, as to have given it the name of the Yellow Fever." Mitchell misdiagnosed the disease that he observed and treated, and the disease was probably Weil's disease or hepatitis. See: Saul Jarcho (1957) "John Mitchell, Benjamin Rush, and Yellow fever". Bulletin of the History of Medicine, 31 (2): 132–6.

[9] Mitchell, John (written: 1744; reprinted: 1814) "Account of the Yellow fever which prevailed in Virginia in the years 1737, 1741, and 1742, in a letter to the late Cadwallader Colden, Esq. of New York, from the late John Mitchell, M.D.F.R.S. of Virginia", American Medical and Philosophical Register, 4: 181–215.

[ReferenceA-9] Bekal S, Domier LL, Gonfa B, McCoppin NK, Lambert KN, Bhalerao K (2014). "A novel flavivirus in the soybean cyst nematode". Journal of General Virology. 95 (Pt 6): 1272–1280. doi:10.1099/vir.0.060889-0. PMID 24643877.

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Flavivirus

A TEM micrograph of Yellow fever virus

Zika virus viral envelope model, colored by chains, PDB entry 5ire^[2]
Virus classification
(unranked):	Virus
Realm:	Riboviria
Kingdom:	Orthornavirae
Phylum:	Kitrinoviricota
Class:	Flasuviricetes
Order:	Amarillovirales
Family:	Flaviviridae
Genus:	*Flavivirus*
Species^[1]
See text