scholarly journals Yellow Fever Virus: Diagnostics for a Persistent Arboviral Threat

2018 ◽  
Vol 56 (10) ◽  
Author(s):  
Jesse J. Waggoner ◽  
Alejandra Rojas ◽  
Benjamin A. Pinsky
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Current Knowledge ◽  
Hemorrhagic Fever ◽  
Clinical Diagnostics ◽  
Fever Virus ◽  
Diagnostic Methods ◽  
Effective Vaccine ◽  
Molecular Testing ◽  
Viral Culture

ABSTRACTYellow fever (YF) is the prototypical hemorrhagic fever and results from infection with yellow fever virus (YFV), which is endemic to regions of Africa and South America. Despite the availability of an effective vaccine, YFV continues to cause disease throughout regions where it is endemic, including intermittent large outbreaks among undervaccinated populations. A number of diagnostic methods and assays have been described for the detection of YFV infection, including viral culture, molecular testing, serology, and antigen detection. Commercial diagnostics are not widely available, and testing is generally performed at a small number of reference laboratories. The goal of this article, therefore, is to review available clinical diagnostics for YFV, which may not be familiar to many practitioners outside areas where it is endemic. Additionally, we identify gaps in our current knowledge about YF that pertain to diagnosis and describe interventions that may improve YFV detection.

scholarly journals Yellow Fever Outbreak in Eastern Senegal, 2020–2021

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1475
Author(s):  
Moussa Moïse Diagne ◽  
Marie Henriette Dior Ndione ◽  
Alioune Gaye ◽  
Mamadou Aliou Barry ◽  
Diawo Diallo ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Mosquito Species ◽  
Virus Transmission ◽  
Genomic Analysis ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
World Health ◽  
Effective Vaccine ◽  
Ministry Of Health

Yellow fever virus remains a major threat in low resource countries in South America and Africa despite the existence of an effective vaccine. In Senegal and particularly in the eastern part of the country, periodic sylvatic circulation has been demonstrated with varying degrees of impact on populations in perpetual renewal. We report an outbreak that occurred from October 2020 to February 2021 in eastern Senegal, notified and managed through the synergistic effort yellow fever national surveillance implemented by the Senegalese Ministry of Health in collaboration with the World Health Organization, the countrywide 4S network set up by the Ministry of Health, the Institut Pasteur de Dakar, and the surveillance of arboviruses and hemorrhagic fever viruses in human and vector populations implemented since mid 2020 in eastern Senegal. Virological analyses highlighted the implication of sylvatic mosquito species in virus transmission. Genomic analysis showed a close relationship between the circulating strain in eastern Senegal, 2020, and another one from the West African lineage previously detected and sequenced two years ago from an unvaccinated Dutch traveler who visited the Gambia and Senegal before developing signs after returning to Europe. Moreover, genome analysis identified a 6-nucleotide deletion in the variable domain of the 3′UTR with potential impact on the biology of the viral strain that merits further investigations. Integrated surveillance of yellow fever virus but also of other arboviruses of public health interest is crucial in an ecosystem such as eastern Senegal.

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

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 960 ◽  
Author(s):  
Robin D.V. Kleinert ◽  
Eduardo Montoya-Diaz ◽  
Tanvi Khera ◽  
Kathrin Welsch ◽  
Birthe Tegtmeyer ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Drug Targets ◽  
Yellow Fever Virus ◽  
Current Knowledge ◽  
Hemorrhagic Fever ◽  
Structural Data ◽  
Host Responses ◽  
Effective Vaccine ◽  
Tropical Regions ◽  
Technological Advances

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.

scholarly journals Yellow Fever Virus Down-Regulates mRNA Expression of SOCS1 in the Initial Phase of Infection in Human Cell Lines

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 802
Author(s):  
Michael B. Yakass ◽  
David Franco ◽  
Osbourne Quaye
Keyword(s):  
Mrna Expression ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Expression Patterns ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Interferon Β ◽  
Infected Cells ◽  
Insight Into

Flaviviruses are constantly evolving diverse immune evasion strategies, and the exploitation of the functions of suppressors of cytokine signalling (SOCS) and protein inhibitors of activated STATs (PIAS) to favour virus replication has been described for Dengue and Japanese encephalitis viruses but not for yellow fever virus (YFV), which is still of global importance despite the existence of an effective vaccine. Some mechanisms that YFV employs to evade host immune defence has been reported, but the expression patterns of SOCS and PIAS in infected cells is yet to be determined. Here, we show that SOCS1 is down-regulated early in YFV-infected HeLa and HEK 293T cells, while SOCS3 and SOCS5 are not significantly altered, and PIAS mRNA expression appears to follow a rise-dip pattern akin to circadian-controlled genes. We also demonstrate that YFV evades interferon-β application to produce comparable viral titres. This report provides initial insight into the in vitro expression dynamics of SOCS and PIAS upon YFV infection and a basis for further investigation into SOCS/PIAS expression and how these modulate the immune response in animal models.

scholarly journals AT-752, a double prodrug of a guanosine nucleotide analog, inhibits yellow fever virus in a hamster model

2021 ◽  
Author(s):  
Kai Lin ◽  
Steven S Good ◽  
Justin G. Julander ◽  
Abbie Weight ◽  
Adel Moussa
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Limit Of Detection ◽  
Virus Titer ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Hamster Model ◽  
Nucleotide Analog

Yellow fever virus (YFV) is a zoonotic pathogen re-emerging in parts of the world, causing a viral hemorrhagic fever associated with high mortality rates. While an effective vaccine is available, having an effective antiviral against YFV is critical against unexpected outbreaks, or when vaccination is not recommended. We have previously identified AT-281, the free base of AT-752, an orally available double prodrug of a guanosine nucleotide analog, as a potent inhibitor of YFV in vitro , with a 50% effective concentration (EC 50 ) of 0.31 µM. In hamsters infected with YFV (Jimenez strain), viremia rose about 4 log 10 -fold and serum alanine aminotransferase (ALT) 2-fold compared to sham-infected animals. Treatment with 1000 mg/kg AT-752 for 7 days, initiated 4 h prior to viral challenge, reduced viremia to below the limit of detection by day 4 post infection (pi) and returned ALT to normal levels by day 6 pi. When treatment with AT-752 was initiated 2 days pi, the virus titer and ALT dropped >2 log 10 and 53% by day 4 and 6 pi, respectively. In addition, at 21 days pi, 70 – 100% of the infected animals in the treatment groups survived compared to 0% of the untreated group (p<0.001). Moreover, in vivo formation of the active triphosphate metabolite AT-9010 was measured in the animal tissues, with the highest concentrations in liver and kidney, organs that are vulnerable to the virus. The demonstrated in vivo activity of AT-752 suggests that it is a promising compound for clinical development in the treatment of YFV infection.

scholarly journals A community-level investigation following a yellow fever virus outbreak in South Omo Zone, South-West Ethiopia

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6466 ◽  
Author(s):  
Ranya Mulchandani ◽  
Fekadu Massebo ◽  
Fekadu Bocho ◽  
Claire L. Jeffries ◽  
Thomas Walker ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Case Fatality ◽  
Public Health Problem ◽  
Fever Virus ◽  
World Health ◽  
Effective Vaccine ◽  
Breeding Sites ◽  
Study Results ◽  
South Omo

Background Despite the availability of a highly effective vaccine, yellow fever virus (YFV) remains an important public health problem across Africa and South America due to its high case-fatality rate. This study investigated the historical epidemiology and contemporary entomological and social determinants of a YFV outbreak in South Omo Zone (SOZ), Ethiopia. Methods A YFV outbreak occurred in SOZ, Ethiopia in 2012–2014. Historical epidemiological data were retrieved from the SOZ Health Department and analyzed. Entomological sampling was undertaken in 2017, including mosquito species identification and molecular screening for arboviruses to understand mosquito habitat distribution, and finally current knowledge, attitudes and preventative practices within the affected communities were assessed. Results From October 2012 to March 2014, 165 suspected cases and 62 deaths were reported, principally in rural areas of South Ari region (83.6%). The majority of patients were 15–44 years old (75.8%) and most case deaths were males (76%). Between June and August 2017, 688 containers were sampled across 180 households to identify key breeding sites for Aedes mosquitoes. Ensete ventricosum (“false banana”) and clay pots outside the home were the most productive natural and artificial breeding sites, respectively. Entomological risk indices classified most sites as “high risk” for future outbreaks under current World Health Organization criteria. Adult mosquitoes in houses were identified as members of the Aedes simpsoni complex but no YFV or other arboviruses were detected by PCR. The majority of community members had heard of YFV, however few activities were undertaken to actively reduce mosquito breeding sites. Discussion Study results highlight the potential role vector control could play in mitigating local disease transmission and emphasize the urgent need to strengthen disease surveillance systems and in-country laboratory capacity to facilitate more rapid responses to future YFV outbreaks.

Outbreak of jaundice and hemorrhagic fever in the Southeast of Brazil in 2001: Detection and molecular characterization of yellow fever virus

2002 ◽  
Vol 68 (4) ◽  
pp. 620-627 ◽  
Author(s):  
A.M.B. de Filippis ◽  
R.M.R. Nogueira ◽  
H.G. Schatzmayr ◽  
D.S. Tavares ◽  
A.V. Jabor ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Hemorrhagic Fever ◽  
Fever Virus

scholarly journals Consumptive coagulopathy of severe yellow fever occurs independently of hepatocellular tropism and massive hepatic injury

2020 ◽  
Vol 117 (51) ◽  
pp. 32648-32656
Author(s):  
Adam L. Bailey ◽  
Liang-I Kang ◽  
Luiz Gonzaga Francisco de Assis Barros D’Elia Zanella ◽  
Cássia G. T. Silveira ◽  
Yeh-Li Ho ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Rhesus Macaques ◽  
Hemorrhagic Fever ◽  
Cell Types ◽  
Viral Disease ◽  
Clotting Factor ◽  
Effective Vaccine ◽  
Hemorrhagic Disease ◽  
Consumptive Coagulopathy

Yellow fever (YF) is a mosquito-transmitted viral disease that causes tens of thousands of deaths each year despite the long-standing deployment of an effective vaccine. In its most severe form, YF manifests as a hemorrhagic fever that causes severe damage to visceral organs. Although coagulopathy is a defining feature of severe YF in humans, the mechanism by which it develops remains uncertain. Hepatocytes are a major target of yellow fever virus (YFV) infection, and the coagulopathy in severe YF has long been attributed to massive hepatocyte infection and destruction that results in a defect in clotting factor synthesis. However, when we analyzed blood from Brazilian patients with severe YF, we found high concentrations of plasma D-dimer, a fibrin split product, suggestive of a concurrent consumptive process. To define the relationship between coagulopathy and hepatocellular tropism, we compared infection and disease inFah−/−,Rag2−/−, andIl2rɣ−/−mice engrafted with human hepatocytes (hFRG mice) and rhesus macaques using a highly pathogenic African YFV strain. YFV infection of macaques and hFRG mice caused substantial hepatocyte infection, liver damage, and coagulopathy as defined by virological, clinical, and pathological criteria. However, only macaques developed a consumptive coagulopathy whereas YFV-infected hFRG mice did not. Thus, infection of cell types other than hepatocytes likely contributes to the consumptive coagulopathy associated with severe YF in primates and humans. These findings expand our understanding of viral hemorrhagic disease and associated coagulopathy and suggest directions for clinical management of severe YF cases.

scholarly journals Ecuador Paraiso Escondido Virus, a New Flavivirus Isolated from New World Sand Flies in Ecuador, Is the First Representative of a Novel Clade in the Genus Flavivirus

2015 ◽  
Vol 89 (23) ◽  
pp. 11773-11785 ◽  
Author(s):  
Cigdem Alkan ◽  
Sonia Zapata ◽  
Laurence Bichaud ◽  
Grégory Moureau ◽  
Philippe Lemey ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Yellow Fever ◽  
New World ◽  
Yellow Fever Virus ◽  
Current Knowledge ◽  
Fever Virus ◽  
Sand Fly ◽  
Surprising Result ◽  
Sand Flies ◽  
Content Type

ABSTRACTA new flavivirus, Ecuador Paraiso Escondido virus (EPEV), named after the village where it was discovered, was isolated from sand flies (Psathyromyia abonnenci, formerlyLutzomyia abonnenci) that are unique to the New World. This represents the first sand fly-borne flavivirus identified in the New World. EPEV exhibited a typical flavivirus genome organization. Nevertheless, the maximum pairwise amino acid sequence identity with currently recognized flaviviruses was 52.8%. Phylogenetic analysis of the complete coding sequence showed that EPEV represents a distinct clade which diverged from a lineage that was ancestral to the nonvectored flaviviruses Entebbe bat virus, Yokose virus, and Sokoluk virus and also theAedes-associated mosquito-borne flaviviruses, which include yellow fever virus, Sepik virus, Saboya virus, and others. EPEV replicated in C6/36 mosquito cells, yielding high infectious titers, but failed to reproduce either in vertebrate cell lines (Vero, BHK, SW13, and XTC cells) or in suckling mouse brains. This surprising result, which appears to eliminate an association with vertebrate hosts in the life cycle of EPEV, is discussed in the context of the evolutionary origins of EPEV in the New World.IMPORTANCEThe flaviviruses are rarely (if ever) vectored by sand fly species, at least in the Old World. We have identified the first representative of a sand fly-associated flavivirus, Ecuador Paraiso Escondido virus (EPEV), in the New World. EPEV constitutes a novel clade according to current knowledge of the flaviviruses. Phylogenetic analysis of the virus genome showed that EPEV roots theAedes-associated mosquito-borne flaviviruses, including yellow fever virus. In light of this new discovery, the New World origin of EPEV is discussed together with that of the other flaviviruses.

scholarly journals Abstract OR-8: Cryo-EM Structure of Mature Yellow Fever Virus

2021 ◽  
Vol 11 (Suppl_1) ◽  
pp. S10-S10
Author(s):  
Valeria Samygina ◽  
Eugene Pichkur ◽  
Peter Cherepanov ◽  
Alexey Egorov ◽  
Aydar Ishmukhametov ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Model Building ◽  
Lipid Membrane ◽  
Yellow Fever Virus ◽  
Hemorrhagic Fever ◽  
Structural Data ◽  
Fever Virus ◽  
Sub Saharan Africa ◽  
Virus Zika ◽  
Severe Jaundice

Background: Yellow fever virus (YFV) is the prototype virus of the genus Flavivirus. It is endemic to sub-Saharan Africa and tropical South America. YF disease ranges from asymptomatic to severe jaundice and hemorrhagic fever. The flavivirus virion core is enveloped by a lipid membrane with integrated membrane (M) proteins and envelope (E) proteins that form the outer surface of the virion. The Е protein provides stability to the viral particle and is responsible for early infection stages. Flaviviruses are heterogeneous in nature, which is related to their maturation process. Samples always contain mature, immature, half-mature, and damaged particles. Thus, cryo-EM is a method of choice for their structure determination. During the early stages of cryo-EM development, structures of flaviviruses were studied at 10–20 Å resolution. However, due to the progress of recent years, it became possible to determine flavivirus structures at a resolution of 5.6-2.6 Å. The cryo-EM method was used to obtain structural data of virions of dengue fever virus, Zika virus, TBE virus, etc. For YFV, only the cryo-EM structure of the immature virions at a low resolution of 25 Å was determined (Y. Zhang et al. 2003 doi:10.1093/emboj/cdg270). However, the structure of mature (most infectious) YFV particles is still unknown. Methods: Virus sample was produced in Vero cell culture. YFV-17D was inactivated and purified using ultracentrifugation. The concentration of viral particles in the target inactivated YFV-17D (iYFV-17D) was evaluated by spectrophotometry and by estimating the concentration of E protein determined by PAGE electrophoresis. Preliminary quality control of iYFV-17D sample was performed using negative staining TEM. Cryo-EM data were collected using cryo-TEM Krios (Thermo-Fisher, USA) at 300kV using DED Falcon II. Dataset was preprocessed using Warp. Further processing was performed in Relion 3.1 and CisTEM. Model building was carried out using Isolde, Phenix and Coot software. Results: A protocol of production and purification of highly concentrated (~2x1012) monodisperse inactivated iYFV-17D sample was developed. Cryo-EM structure of mature iYFV was solved at 4.1 Å resolution. The structure of YFV is similar to other known flavivirus structures, with 180 copies of protein E arranged in a herringbone pattern that makes up the icosahedral shell. Conclusion: The high-resolution structure of mature iYFV-17D allowed to elucidate special features of this flavivirus and may be useful for vaccine improvement and drug development.

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