''Flaviviridae'' is a family of enveloped

positive-strand RNA virus Positive-strand RNA viruses (+ssRNA viruses) are a group of related viruses that have positive-sense, single-stranded genomes made of ribonucleic acid. The positive-sense genome can act as messenger RNA (mRNA) and can be directly translated int ...

es which mainly infect

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

s and

bird Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweigh ...

s. They are primarily spread through

arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a Segmentation (biology), segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and Arth ...

vectors (mainly

tick Ticks (order Ixodida) are parasitic arachnids that are part of the mite superorder Parasitiformes. Adult ticks are approximately 3 to 5 mm in length depending on age, sex, species, and "fullness". Ticks are external parasites, living by ...

s and

mosquito Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meaning " gnat"). The word "mosquito" (formed by ''mosca'' and diminutive ''-ito'') is Spanish for "li ...

es). The family gets its name from the

yellow fever Yellow fever is a viral disease of typically short duration. In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains – particularly in the back – and headaches. Symptoms typically improve within five days. In ...

virus; ''flavus'' is Latin for "yellow", and yellow fever in turn was named because of its propensity to cause

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

in victims. There are 89 species in the family divided among four genera. Diseases associated with the group include:

hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

(

hepacivirus ''Hepacivirus'' is a genus of positive-strand RNA viruses in the family ''Flaviviridae''. The hepatitis C virus (HCV), in species '' Hepacivirus C'', infects humans and is associated with hepatitis and hepatocellular carcinoma. There are fourt ...

es), hemorrhagic syndromes, fatal mucosal disease (

pestivirus ''Pestivirus'' is a genus of viruses, in the family ''Flaviviridae''. Viruses in the genus ''Pestivirus'' infect mammals, including members of the family Bovidae (which includes cattle, sheep, and goats) and the family Suidae (which includes v ...

es),

hemorrhagic fever Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses in which fever and hemorrhage are caused by a viral infection. VHFs may be caused by five distinct families of RNA viruses: the families ''Filoviridae'', ''Flav ...

encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, ...

, and the birth defect

microcephaly Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...

(

flavivirus ''Flavivirus'' 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 cau ...

es).

Structure

Virus particles are enveloped and spherical with icosahedral-like geometries that have pseudo T=3 symmetry. They are about 40–60 nm in diameter.

Genome

Members of the family ''Flaviviridae'' have monopartite, linear, single-stranded

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

genomes In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding gen ...

of positive polarity, and 9.6 to 12.3 kilobase in total length. The 5'-termini of flaviviruses carry a

methylated In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These ...

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...

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

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 Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. Whe ...

-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 virus exits the host cell by budding. Humans and mammals serve as the natural hosts. The virus is transmitted via vectors (ticks and mosquitoes).

Taxonomy

The family has four genera: *Genus ''

Flavivirus ''Flavivirus'' 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 cau ...

'' (includes ''

Dengue virus ''Dengue virus'' (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family ''Flaviviridae''; genus ''Flavivirus''. Four serotypes of the virus have been found, a reported fifth has yet to be co ...

'', ''

Japanese encephalitis Japanese encephalitis (JE) is an infection of the brain caused by the Japanese encephalitis virus (JEV). While most infections result in little or no symptoms, occasional inflammation of the brain occurs. In these cases, symptoms may include he ...

'', '' Kyasanur Forest disease'', '' Powassan virus'', ''

West Nile virus West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family ''Flaviviridae'', from the genus ''Flavivirus'', which also contains the Zika virus, dengue virus, and yellow fever virus. The virus ...

'', ''

Yellow fever virus Yellow fever is a viral disease of typically short duration. In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains – particularly in the back – and headaches. Symptoms typically improve within five days. In ...

'', and ''

Zika virus ''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active ''Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, whe ...

'') *Genus ''

Hepacivirus ''Hepacivirus'' is a genus of positive-strand RNA viruses in the family ''Flaviviridae''. The hepatitis C virus (HCV), in species '' Hepacivirus C'', infects humans and is associated with hepatitis and hepatocellular carcinoma. There are fourt ...

'' (includes ''Hepacivirus C'' (

hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepato ...

) and ''Hepacivirus B'' (GB virus B)) *Genus ''

Pegivirus ''Pegivirus'' is the approved name for a genus of single positive-stranded RNA viruses in the family ''Flaviviridae''. The name is a derived one: "Pe" stands for "persistent" and "g" is a reference to Hepatitis G, a former name of the ''C'' s ...

'' (includes ''Pegivirus A'' (GB virus A), ''Pegivirus C'' (GB virus C), and ''Pegivirus B'' (GB virus D)) *Genus ''

Pestivirus ''Pestivirus'' is a genus of viruses, in the family ''Flaviviridae''. Viruses in the genus ''Pestivirus'' infect mammals, including members of the family Bovidae (which includes cattle, sheep, and goats) and the family Suidae (which includes v ...

'' (includes ''Pestivirus A'' ( bovine viral diarrhea virus 1) and ''Pestivirus C'' (

classical swine fever virus Classical may refer to: European antiquity *Classical antiquity, a period of history from roughly the 7th or 8th century B.C.E. to the 5th century C.E. centered on the Mediterranean Sea *Classical architecture, architecture derived from Greek and ...

, previously hog cholera virus)). Viruses in this genus infect nonhuman mammals. ;Unclassified Other flaviviruses are known that have yet to be classified. These include Wenling shark virus.

Jingmenvirus Jingmenvirus is a group of positive-sense single-stranded RNA viruses with segmented genomes. They are primarily associated with arthropods and are one of only two known segmented RNA viruses that infect animal hosts. The first member of the gro ...

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 4 or 5 pieces. Two of these segments are derived from flaviviruses. 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.

Clinical importance

Major diseases caused by members of the family ''Flaviviridae'' include:

References

External links

ICTV Report: ''Flaviviridae''

Flaviviridae Genomes
database search results from th
Viral Bioinformatics Resource Center

Virus Pathogen Database and Analysis Resource (ViPR): Flaviviridae
* {{Authority control Virus families Riboviria