Yellow Fever Virus: Knowledge Gaps Impeding the Fight Against an Old Foe. Issue 11 (November 2018)

• Record Type: Journal Article
• Authors: Douam, Florian; Ploss, Alexander
• Is Part Of: Trends in microbiology. Volume 26:Issue 11(2018)
• Page Start: 913
• Page End: 928
• Publication Date: 2018-11
• Subjects: yellow fever -- yellow fever virus -- yellow fever vaccine -- flaviviruses -- viral pathogenesis; Microbiology -- Periodicals; Infection -- Periodicals; Virulence (Microbiology) -- Periodicals; Infection -- Periodicals; Microbiology -- Periodicals; Virulence -- Periodicals; Microbiologie -- Périodiques; Infection -- Périodiques; Virulence (Microbiologie) -- Périodiques; Infection; Microbiology; Virulence (Microbiology); 579
• DOI: 10.1016/j.tim.2018.05.012
• Languages: English
• ISSNs: 0966-842X

Abstract

Abstract : Yellow fever (YF) was one of the most dangerous infectious diseases of the 18th and 19th centuries, resulting in mass casualties in Africa and the Americas. The etiologic agent is yellow fever virus (YFV), and its live-attenuated form, YFV-17D, remains one of the most potent vaccines ever developed. During the first half of the 20th century, vaccination combined with mosquito control eradicated YFV transmission in urban areas. However, the recent 2016–2018 outbreaks in areas with historically low or no YFV activity have raised serious concerns for an estimated 400–500 million unvaccinated people who now live in at-risk areas. Once a forgotten disease, we highlight here that YF still represents a very real threat to human health and economies. As many gaps remain in our understanding of how YFV interacts with the human host and causes disease, there is an urgent need to address these knowledge gaps and propel YFV research forward. Highlights: Intense yellow fever virus (YFV) re-emergence events have been recently reported in Africa and South America, and vaccine shortage triggered significant concerns in our ability to prevent future outbreaks. The host-dependency of yellow fever (YF) are poorly understood and limit the development of antiviral therapies. Liver disease and immune dysregulations are thought to be major drivers of YF pathogenesis. Recent insights into the human immune response to YFV-17D have helped to profile the cellular responses that define a potent vaccine. Key differences between YFV-17D and wild-type YFV infection have been uncovered, but the molecular mechanisms governing YFV immunogenicity and pathogenicity in vivo are unknown. Recent advances in genomics and humanized animal models open a new and unprecedented path for YF research.