Yellow fever virus is an enveloped, positive-sense single-stranded RNA virus in the genus Flavivirus. It is transmitted by Aedes and Haemagogus mosquitoes and causes yellow fever, an acute hemorrhagic disease characterised by fever, jaundice and bleeding.
Genome and Virology
The yellow fever virus genome is about 11 kilobases long and encodes a single open reading frame. The translated polyprotein is cleaved into three structural proteins (capsid, premembrane/membrane and envelope) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). The envelope glycoprotein binds to host cell receptors on dendritic cells and hepatocytes; virions enter via receptor-mediated endocytosis, and acidification of endosomes triggers fusion. Replication occurs on endoplasmic reticulum membranes, where NS3 acts as a serine protease and helicase and NS5 functions as the RNA-dependent RNA polymerase and methyltransferase synthesising negative-strand intermediates and progeny genomes. Assembly of immature particles in the endoplasmic reticulum is followed by maturation in the Golgi apparatus and release by exocytosis. Yellow fever virus replicates efficiently in hepatocytes, dendritic cells and macrophages in primates, and in midgut and salivary glands of mosquitoes. Genetic diversity is divided into African and South American lineages, reflecting historical spread from Africa to the Americas.
Epidemiology and Vaccination
Yellow fever has caused devastating epidemics since the seventeenth century. The virus is maintained in a sylvatic cycle involving non-human primates and forest-dwelling mosquitoes such as Haemagogus and Aedes species, and in an urban cycle between humans and Aedes aegypti. The disease is endemic in tropical regions of sub-Saharan Africa and South America, where thousands of cases occur annually. Clinical infection has an incubation period of 3–6 days followed by fever, headache, myalgia and nausea; a toxic phase develops in a subset of patients with jaundice, coagulopathy, hemorrhage and shock. Case fatality among severe cases ranges from 20 % to 50 %. There is no specific antiviral therapy, but a safe and effective live attenuated vaccine (17D strain) provides long-lasting immunity and is the cornerstone of prevention. Vaccination campaigns and vector control have reduced urban outbreaks, but lapses in immunity and sylvatic spillover continue to cause periodic epidemics. Rare adverse events of vaccination include viscerotropic and neurologic disease, especially in individuals with thymic disorders or compromised immunity.
Yellow fever virus remains a threat in regions where vaccination coverage and vector control are inadequate. Continuous surveillance, maintenance of vaccine stockpiles and strengthening of immunisation programmes are critical to prevent future outbreaks.
Related Terms: West Nile Virus, Dengue Virus, Japanese Encephalitis Virus, Yellow Fever Vaccine, Aedes aegypti