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Yellow Fever Virus Antiviral Services

Yellow fever virus belongs to the genus Flavivirus of the Flaviviridae family. The virus particles are spherical, 37-50 nm in diameter, with a lipid envelope and spinous process on the surface. Its genome is a single-stranded positive-sense RNA with a total length of about 11 kb, encoding 3 structural proteins and 7 non-structural proteins. Yellow fever is endemic in tropical regions of Africa and South America and is mainly transmitted among non-human primates by mosquitoes. Although YFV infection is asymptomatic in most non-human primates (except for some New World monkeys), severe cases can also cause illness in humans with a mortality rate of 20% in Africa and as high as 60% in South America. The main feature of YF disease is a period of flu-like symptoms and then may become more severe. Since there is no cure for YF, a mass vaccination campaign using a vaccine known as YFV-17D, a highly effective live-attenuated YFV vaccine, is currently the only weapon available to fight the disease and prevent future outbreaks.

Biosafety level 3 practices and facilities are recommended for work involving wild-type yellow fever virus, while biosafety level 2 practices and facilities are recommended for work involving yellow fever 17D virus. Detection of YFV-specific IgM is considered conclusive confirmation of YF in the absence of recent YF vaccination and a negative diagnosis of other flaviviruses (including IgM antibodies). However, more robust corroboration of YFV infection is provided by immunohistochemical detection of YFV antigen, amplification of YFV genomic sequences from blood or solid tissue, or by viremia testing involving culture of YFV infectious particles. Plaque reduction neutralization test (PRNT) or virus neutralization test (VNT) is the most specific method for detecting YFV antibodies, and it is also the current gold standard for the differential diagnosis of flavivirus. Hemagglutination inhibition (HI) and complement fixation (CF) methods have been used in the serological diagnosis of YF in the past, but they have been used less frequently in recent years because they are non-discriminant of the IgM/IgG antibody class and perform poorly in comparison to alternative assays. Other assays currently used to detect YFV IgM and IgG antibodies include in-house indirect immunofluorescence methods (IIF), ELISA, MAC-ELISA, and ELISA inhibition tests.

Yellow-fever-virus-life-cycleFigure 1. Yellow fever virus life cycle.

The replication cycle of YFV consists of several distinct stages (Figure 1). These steps include binding of viral particles to target cells; interaction with surface receptors to internalize the virus; fusion of viral and endosomal membranes and release of the nucleocapsid into the cytoplasm; disassembly of the nucleocapsid; translation and replication of the viral genome; assembly and maturation of viral particles; release of nascent virions.

Vaccination is currently the only way to control and prevent the spread of YFV in endemic areas. In fact, despite a long history of human affliction with YFV and large populations in tropical Africa and Central and South America at risk of potentially catastrophic epidemics, today, treatment options for those infected are limited to relieving symptoms and treating severely ill patients with intensive care support. Currently, there are no specific licensed treatment regimens for YFV-related serious diseases. As YFV remains a significant public health threat, the development of antiviral therapies to treat infected individuals remains urgent. Creative Diagnostics has extensive knowledge to support clients in yellow fever virus antiviral research and development.

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References:

  1. Zandi, K., Amblard, F., Amichai, S., Bassit, L., Tao, S., Jiang, Y., ... & Schinazi, R. F. (2019). Nucleoside analogs with antiviral activity against yellow fever virus. Antimicrobial agents and chemotherapy, 63(9), e00889-19.
  2. Kleinert, R. D., Montoya-Diaz, E., Khera, T., Welsch, K., Tegtmeyer, B., Hoehl, S., ... & Brown, R. J. (2019). Yellow fever: Integrating current knowledge with technological innovations to identify strategies for controlling a re-emerging virus. Viruses, 11(10), 960.
  3. Domingo, C., Charrel, R. N., Schmidt-Chanasit, J., Zeller, H., & Reusken, C. (2018). Yellow fever in the diagnostics laboratory. Emerging Microbes & Infections, 7(1), 1-15.

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Antiviral Services - Creative Diagnostics

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