Abstract
Yellow fever virus (YFV) represents a re-emerging zoonotic pathogen, transmitted by mosquito vectors to humans from primate reservoirs. Sporadic outbreaks of YFV occur in endemic tropical regions, causing a viral hemorrhagic fever (VHF) associated with high mortality rates. Despite a highly effective vaccine, no antiviral treatments currently exist. Therefore, YFV represents a neglected tropical disease and is chronically understudied, with many aspects of YFV biology incompletely defined including host range, host–virus interactions and correlates of host immunity and pathogenicity. In this article, we review the current state of YFV research, focusing on the viral lifecycle, host responses to infection, species tropism and the success and associated limitations of the YFV-17D vaccine. In addition, we highlight the current lack of available treatments and use publicly available sequence and structural data to assess global patterns of YFV sequence diversity and identify potential drug targets. Finally, we discuss how technological advances, including real-time epidemiological monitoring of outbreaks using next-generation sequencing and CRISPR/Cas9 modification of vector species, could be utilized in future battles against this re-emerging pathogen which continues to cause devastating disease.
Highlights
General IntroductionYellow fever was historically the first described viral hemorrhagic fever (VHF) and its causative agent, the yellow fever virus (YFV), is the prototypic member of the family Flaviviridae
Division of Veterinary Medicine, Paul-Ehrlich-Institute, 63225 Langen, Germany; Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Essen, Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research;
Yellow fever virus (YFV) is a member of the Flavivirus genus, which is composed of arboviruses exhibiting broad host ranges which can be animal reservoirs via insect vectors
Summary
Yellow fever was historically the first described viral hemorrhagic fever (VHF) and its causative agent, the yellow fever virus (YFV), is the prototypic member of the family Flaviviridae. YFV is a member of the Flavivirus genus, which is composed of arboviruses exhibiting broad host ranges which can be animal reservoirs via insect vectors. Despite long-standing knowledge of YFVs genomic architecture, favorable growth kinetics in tissue culture and the availability of reverse genetic systems [19,20,21,22,23,24], YFV remains a neglected tropical disease attracting relatively little research attention [25] This is, in part, due to vaccine availability, which has led to research complacency [3], and recent commentaries have highlighted the need for intensification of YFV research, as many facets of the virus life cycle remain poorly defined [26,27]. These include determination of vertebrate and arthropod host-ranges, identification of co-opted host factors which are essential for YFV propagation in humans and insects, and identification of genetic markers and associated mechanisms underlying differential pathogenesis and observed clinical outcomes in infected humans
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