Yellow fever virus
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The yellow fever virus (also yellow fever virus ; English Yellow Fever Virus , short YFV) is a virus that in humans and other primates , a hemorrhagic fever , known as the yellow fever can trigger. The virus is transmitted by mosquitoes of various genera (including Aedes , Haemagoggus and Sabethes ). When an infected primate bites, the mosquito ingests the virus, which then multiplies in the mosquito and infects the salivary glands. It is passed on through the saliva with the next bite.
The yellow fever virus belongs to the Flaviviridae family , whose members typically have a single-stranded RNA with positive polarity as a genome , which is surrounded by a spherical capsid . The capsid is from one of the host cell derived membrane wrapped, in which the structural proteins M and E are stored. Protein E in particular is prominent on the surface of the virion (virus particle) and therefore acts as an antigen .
Both the name of the genus Flavivirus and the name of the entire Flaviviridae family are derived from the yellow fever virus (from Latin flavus , "yellow").
Systematics
The yellow fever virus is the type species of the Flaviviridae family , which is divided into the genera Flavivirus , Pestivirus and Hepacivirus . Over 50 viruses are classified in the genus Flavivirus , with the yellow fever virus falling into the mosquito-borne virus category. Together with the Banzi virus , the Bouboui virus , the Edge Hill virus , the Jugra virus , the Saboya virus , the Sepik virus , the Uganda S virus and the Wesselsbron virus, it forms the “yellow fever virus ” -Group". All of these viruses originate from the ancient world, use mosquitoes of the genus Aedes as vectors and infect mammals .
structure
The virions (virus particles) of the YFV are spherical and have a diameter of approximately 40-50 nm. The genome is complexed with the dimerized capsid protein C as a nucleocapsid . The capsid is enveloped by a membrane derived from the host cell, in which the structural proteins M and E are embedded. Protein E in particular is prominent on the surface of the virion and therefore acts as an antigen , with 12 epitopes being identified on protein E alone. The protein consists of three domains, whereby antibodies are mainly formed against the DIII lying on the surface as well as against the functionally important fusion loop on DII.
Other viruses of the genus Flavivirus have an icosahedral symmetry, which is why a corresponding structure is also assumed for the yellow fever virus. In the infectious virion, the 90 E dimers would form a pseudo-icosahedral structure with a triangulation number T = 3.
Genome
The RNA genome is complexed with the dimerized capsid protein C as a nucleocapsid . The positive-stranded RNA is about 11,000 nucleotides long and includes only one open reading frame that codes for a polyprotein . Proteases cut this polyprotein into three structural (C, prM, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5); the list corresponds to the arrangement of the genes coding for the proteins on the genome. The RNA has a 5 'cap structure .
In the 17D vaccine virus, the genome contains exactly 10,862 nucleotides, which code for a 3411 amino acid long polyprotein. Only 32 of these almost 3500 amino acids are changed compared to the wild-type virus.
Replication
The viruses infect monocytes , macrophages and dendritic cells , among others . They attach to the cell surface via as yet unidentified receptors and are absorbed by a forming endosome vesicle via clathrin and Rab5- mediated endocytosis . Inside the endosome, the acidic pH induces the fusion of the endosome membrane and the virus envelope . This causes the capsid to enter the cytosol , disintegrate, and release the genome. Both the receptor binding and membrane fusion, by the protein E catalyzes that changes its conformation at an acidic pH, which leads to that the 90 homo dimeric irreversibly 60 Homo trimeric reorganize. The highly conserved hydrophilic fusion loop (domain 2, DII) of the E protein is brought to the surface of the virion. This domain inserts into the host membrane and protein E folds back on itself, bringing the two membranes into direct contact.
After penetration into the host cell , the viral genome in the rough ER and in so-called vesicle packets replicated . Within the ER, an immature form of the virus particles is first produced, in which the M protein has not yet been cleaved by a maturation step and is present as prM ( precursor M ) in a complex with E. The immature particles are processed in the Golgi apparatus by the host protein furin , which cuts prM into M. As a result, E is released from the complex with M, dimerizes and can take its place in the mature (mature), infectious virion.
Non-structural proteins
The yellow fever virus has seven non-structural proteins whose function is only partially understood.
The viral protease is a serine protease with His - Asp - Ser as a catalytic triad and consists of the subunits NS2B and NS3. In addition, NS3 also has a helicase / NTPase activity, which is very likely needed to break up secondary structures in the RNA so that the RNA replication can take place. NS3 is also necessary to create the 5'-cap structure at the beginning of the viral RNA.
The viral RNA-dependent RNA polymerase (RdRP) is the protein NS5. This protein is suitable as a target for antiviral drugs because human cells do not have any equivalent proteins (replication of RNA does not normally take place in eukaryotic cells). Furthermore NS5 also has a methyltransferase - domain containing the 5'-cap structure methylated at N7 and the first nucleotide at the O2.
Reporting requirement
In Germany, direct or indirect evidence of the yellow fever virus must be reported by name in accordance with Section 7 of the Infection Protection Act if the evidence indicates an acute infection.
In Switzerland, the positive and negative laboratory analysis findings to be yellow fever virus notifiable and that after the Epidemics Act (EpG) in connection with the epidemic Regulation and Annex 3 of the Regulation of EDI on the reporting of observations of communicable diseases of man .
Individual evidence
- ↑ ICTV Master Species List 2018b.v2 . MSL # 34, March 2019
- ↑ a b c d ICTV: ICTV Taxonomy history: Yellow fever virus , EC 51, Berlin, Germany, July 2019; Email ratification March 2020 (MSL # 35)
- ^ Gould EA, Solomon T: Pathogenic flaviviruses . In: The Lancet . 371, No. 9611, February 2008, pp. 500-9. doi : 10.1016 / S0140-6736 (08) 60238-X . PMID 18262042 .
- ↑ a b c Pierson TC, Diamond MS: Molecular mechanisms of antibody-mediated neutralization of flavivirus infection . In: Expert Rev Mol Med. . 10, No. 12, May 2008. doi : 10.1017 / S1462399408000665 . PMID 18471342 .
- ↑ a b c d e Sampath A, Padmanabhan R: Molecular targets for flavivirus drug discovery . In: Antiviral Research . 81, No. 1, January 2009, pp. 6-15. doi : 10.1016 / j.antiviral.2008.08.004 . PMID 18796313 .
- ↑ Susanne Modrow, Dietrich Falke, Uwe Truyen: Molecular Virology - An Introduction for Biologists and Physicians , 2nd Edition, Spektrum Akademischer Verlag, 2002, ISBN 382741086X , p. 182.