Yellow Fever - Cause

Cause

Yellow fever is caused by the yellow fever virus, a 40 to 50 nm wide enveloped RNA virus belonging to the family Flaviviridae. The positive sense single-stranded RNA is approximately 11,000 nucleotides long and has a single open reading frame encoding a polyprotein. Host proteases cut this polyprotein into three structural (C, prM, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5); the enumeration corresponds to the arrangement of the protein coding genes in the genome. The viruses infect, amongst others, monocytes, macrophages and dendritic cells. They attach to the cell surface via specific receptors and are taken up by an endosomal vesicle. Inside the endosome, the decreased pH induces the fusion of the endosomal membrane with the virus envelope. Thus, the capsid reaches the cytosol, decays and releases the genome. Receptor binding as well as membrane fusion are catalyzed by the protein E, which changes its conformation at low pH, which causes a rearrangement of the 90 homodimers to 60 homotrimers.

After entering the host cells, the viral genome is replicated in the rough endoplasmic reticulum (ER) and in the so-called vesicle packets. At first, an immature form of the virus particle is produced inside the ER, whose M-protein is not yet cleaved to its mature form and is therefore denoted as prM (precursor M) and forms a complex with protein E. The immature particles are processed in the Golgi apparatus by the host protein furin, which cleaves prM to M. This releases E from the complex which can now take its place in the mature, infectious virion.