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Yellow Fever: Integrating Current Knowledge with Technological Innovations to Identify Strategies for Controlling a Re-Emerging Virus

1
Division of Veterinary Medicine, Paul-Ehrlich-Institute, 63225 Langen, Germany
2
Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
3
University of Veterinary Medicine Hannover, 30559 Hannover, Germany
4
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
5
Institute of Medical Virology, University Hospital Frankfurt, 60596 Frankfurt am Main, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Viruses 2019, 11(10), 960; https://doi.org/10.3390/v11100960
Received: 30 August 2019 / Revised: 30 September 2019 / Accepted: 11 October 2019 / Published: 17 October 2019
(This article belongs to the Special Issue Flavivirus Replication and Pathogenesis)
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. View Full-Text
Keywords: yellow fever virus; flavivirus entry factor; global diversity; yellow fever virus tropism; animal models; transmission and vector control; vaccine; host immune response; E protein structure; re-emerging virus yellow fever virus; flavivirus entry factor; global diversity; yellow fever virus tropism; animal models; transmission and vector control; vaccine; host immune response; E protein structure; re-emerging virus
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Kleinert, R.D.; Montoya-Diaz, E.; Khera, T.; Welsch, K.; Tegtmeyer, B.; Hoehl, S.; Ciesek, S.; Brown, R.J. Yellow Fever: Integrating Current Knowledge with Technological Innovations to Identify Strategies for Controlling a Re-Emerging Virus. Viruses 2019, 11, 960.

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