Flaviviridae

The Flaviviridae or flaviviruses (from Latin flavus, "yellow" - based on the yellow fever virus) represent a family of viruses that all contain single-stranded RNA and are therefore taxonomically assigned to the RNA viruses. The type species of the entire family is the yellow fever virus. All representatives of this family possess a genomic RNA (gRNA) which is packaged in a capsid formed by the C protein. The capsid contains homodimers of the E protein, which are spike-like and serve for adsorption to the host cell. Furthermore, the viral envelope contains lipids from the original host cell and other viral proteins such as the M protein. The viruses multiply in the cytoplasm of the host cell. They are stable in the pH range of 7 to 9.

The genomic RNA (gRNA) is packaged in a capsid formed by the C protein. Homodimers of the E protein are found in the capsid, which serve to adsorb to the host cell. Also localized in the envelope is the matrix protein M. It is stored together with the E protein to form a heterodimer.

The genomic linear ss (+) RNA (9.5-107 Kb) has a size of 40-50nm and is packed in an icosahedral capsid formed by the C protein. In the capsule of the virion there are homodimers of the E-protein. These bud-like protrusions serve for absorption into the host protein. The capsule of the virion also contains the M-matrix proteins, which are combined with the E-proteins to form heterodimers. After adsorption on the cell surface, the virus replicates endocytotically. Subsequently, the virus envelope fuses with the endosomal membrane of the host cell. After release of the positive-stranded RNA, it is translated into a single polyprotein on ribosomes. This is cleaved in the endoplasmic reticulum. Starting from the invaded RNA genome, new viral RNA as well as envelope proteins are formed via various copying processes, so that a new virus can be created.

The Flaviviridae family includes the genera (International Committee on Taxonomy of Viruses (ICTV), as of November 2018):

• Flavivirus (formerly Arbovirus B)
• Hepacivirus
• Pegivirus and
• Pestivirus

Genus Flavivirus: The pathogens of the genus Flavivirus cause a large number of viral infections in both humans and animals. The following species are of pathogenic relevance:

• Yellow fever virus: Yellow fever virus (YFV) Disease - Yellow fever
• Dengue virus: (DENV) Disease - dengue fever
• Tick-borne encephalitis virus (TBEV) Disease - Tick-borne encephalitis
• Japanese encephalitis virus (JEV) Disease - Japanese B encephalitis
• Louping ill virus (Louping-ill virus, LIV) Disease - Encephalitis
• Species Usutu virus (USUV) Disease - often fatal in birds, few or no symptoms in humans
• West Nile virus (WNV) Disease - West Nile fever
• Zika virus (ZIKV) disease - Zika fever
• Kyasanur Forest Disease Virus (KFDV) - Kyasanur Forest Disease
• Alkhurma hemorrhagic fever virus (AHFV)

Genus Hepacivirus

• Hepacivirus A
• Hepacivirus B (GB virus B)
• Hepacivirus C (hepatitis C virus, HCV) - most important representative; disease: hepatitis C
• Hepacivirus D to N

Genus Pegivirus (in drug addicts; associated with an increased risk of lymphoma (Fama A et al. 2020)

• Pegivirus A-K (GB virus A-K), infects New World monkeys, occasionally also humans
• Pegivirus C (GBV-C, also human pegivirus, HPgV and hepatitis G virus) Disease - in humans, the virus was found in connection with a hepatitis C infection; mainly spread among drug addicts.
• Pegivirus H (obsolete: Human hepegivirus, HHPgV or HPgV-2) Disease - was discovered in drug addicts. Significance unclear (Kandathil AJ et al. 2017).
• Pegivirus I to Pegivirus K (unclear significance)

Genus Pestivirus (exclusively pathogenic for animals - Schweizer M et al. 2014)

• Pestivirus C (classical swine fever virus, SP virus) Disease: Trigger of classical swine fever

1. Fama A et al. (2020) Human Pegivirus Infection and Lymphoma Risk: A Systematic Review and Meta-analysis. Clin Infect Dis 71:1221-1228.
2. Hof H et al (2019) Medical Microbiology. Thieme Verlag Stuttgart pp 212-213
3. Kandathil AJ et al (2017) Presence of human hepegivirus-1 in a cohort of people who inject drugs. Ann Intern Med 167:1-7.
4. Schweizer M et al (2014) Pestiviruses. Annu Rev Anim Biosci2:141-163.