Yellow fever virus

The yellow fever virus is a virus that can hemorrhagic fever, the so-called yellow fever trigger, in humans and other primates. The virus is transmitted by mosquitoes of various species (including Aedes, Haemagoggus and Sabethes ). When piercing a primates infected the mosquito picks up the virus, which then propagated further in the mosquito and infects the salivary glands. About the saliva, it is passed in the next stitch.

Yellow fever virus belongs to the Flaviviridae family, whose members typically have a single stranded RNA genome of positive polarity than that is surrounded by a spherical capsid. The RNA genome is dimerized with the capsid protein C complexed before nucleocapsid. The capsid is surrounded by a membrane derived from the host cell in which the structural proteins M and E are stored. In particular, the protein E is prominent on the surface of the virion and therefore acts as an antigen.

Positivsträngige the RNA about 11,000 nucleotides in length and comprises only one open reading frame encoding a polyprotein. Proteases cut, this polyprotein into three structural (C, prM, E) and the seven non-structural proteins ( NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5 ); the list corresponds to the arrangement of the coding for the proteins of genes on the genome.

System

The yellow fever virus is the type species of the Flaviviridae family, which is divided into the genera Flavivirus, Pestivirus and hepacivirus. In the genus Flavivirus 50 viruses are classified, wherein the yellow fever virus falls under the category of viruses transmitted by mosquitoes. It, together with the Banzi virus, Bouboui virus, the Edge Hill virus, Yugra virus, Saboya virus, the Sepik virus, the Uganda S virus and the Wesselsbron virus the " yellow fever virus group ". All of these viruses originate from the old world, mosquitoes of the genus Aedes use as vectors and infect mammals.

Both the name of the genus Flavivirus and the name of the family Flaviviridae is derived from the yellow fever virus from (from Latin flavus, "yellow" ).

Structure

The virion is a spherical and has a diameter of about 40-50 nm, the genome is complexed with the dimerized capsid protein C before and nucleocapsid. The capsid is surrounded by a membrane derived from the host cell in which the structural proteins M and E are stored. In particular, the protein E is prominent on the surface of the virion and therefore acts as an antigen, said 12 epitopes have been identified on the protein E alone. The protein consists of three domains, antibodies primarily against the lying on the surface of DIII and against the functionally important fusion loop are formed on DII.

Other viruses of the genus flavivirus have icosahedral symmetry, and therefore a suitable structure is assumed for the yellow fever virus. In the infectious virion, the E- 90 dimers would form a pseudo- icosahedral structure with Triangulationszahl T = 3.

Genome

Positivsträngige the RNA about 11,000 nucleotides in length and comprises only one open reading frame encoding a polyprotein. Proteases cut, this polyprotein into three structural (C, prM, E) and the seven non-structural proteins ( NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5 ); the list corresponds to the arrangement of the coding for the proteins of genes on the genome. RNA has a 5 'cap structure.

When 17D vaccine virus genome comprises just 10,862 nucleotides that encode long polyprotein for a 3411 amino acids. Only 32 of these nearly 3500 amino acids are altered compared to the wild -type virus.

Replication

Viruses infect inter alia monocytes, macrophages and dendritic cells. They attach to via as yet unidentified receptors on the cell surface and are carried to a ausbildendes Endosomvesikel via clathrin and Rab5 -mediated endocytosis. Inside the endosome, the acidic pH induces the fusion of endosome membrane and the viral envelope. Thus, the capsid reaches the cytosol, decays and releases the genome freely. Both the receptor binding and membrane fusion are catalyzed by the protein E, which at acidic pH alters its conformation, which leads to regroup the 90 homodimers to 60 homotrimers irreversible. The highly conserved hydrophilic fusion loop ( domain 2, DII ) of the E protein is brought to the surface of the virion. This domain inserted into the host membrane and the protein E folds back on itself, which brings the two membranes into direct contact.

After penetration into the host cell, the viral genome is replicated in the rough ER and in so-called vesicle packets. Within the ER an immature form of the virus particle is first produced, in which the M protein was not cleaved by a maturation step and 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 cleaves prM to M. Thus E is released from the complex with M, dimerizes and can take his place at the ripe ( 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 a His- Asp-Ser as a catalytic triad, consisting of the subunits NS2B and NS3. In addition, NS3 is a helicase / NTPase activity, which is very likely to be required to dissolve the secondary structure in the RNA so that the RNA replication can vonstattengehen. NS3 is further necessary to create the 5 'cap - structure at the beginning of the viral RNA.

The viral RNA -dependent RNA polymerase ( RdRp ) is, to the NS5 protein. This protein is suitable as a target for antiviral drugs because human cells have no equivalent proteins ( replication of RNA normally found in eukaryotic cells instead ). NS5 further has a methyltransferase domain comprising the 5 ' methylated cap structure at the N7 and the first nucleotide at O2.