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Trends in Microbiology Nov 2018Yellow 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... (Review)
Review
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.
Topics: Africa; Animals; Disease Models, Animal; Disease Outbreaks; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Host-Pathogen Interactions; Humans; Mosquito Control; RNA, Viral; South America; Vaccination; Vaccines, Attenuated; Yellow Fever; Yellow Fever Vaccine; Yellow fever virus
PubMed: 29933925
DOI: 10.1016/j.tim.2018.05.012 -
Flavivirus NS1 Triggers Tissue-Specific Vascular Endothelial Dysfunction Reflecting Disease Tropism.Cell Reports Feb 2019Flaviviruses cause systemic or neurotropic-encephalitic pathology in humans. The flavivirus nonstructural protein 1 (NS1) is a secreted glycoprotein involved in viral...
Flaviviruses cause systemic or neurotropic-encephalitic pathology in humans. The flavivirus nonstructural protein 1 (NS1) is a secreted glycoprotein involved in viral replication, immune evasion, and vascular leakage during dengue virus infection. However, the contribution of secreted NS1 from related flaviviruses to viral pathogenesis remains unknown. Here, we demonstrate that NS1 from dengue, Zika, West Nile, Japanese encephalitis, and yellow fever viruses selectively binds to and alters permeability of human endothelial cells from lung, dermis, umbilical vein, brain, and liver in vitro and causes tissue-specific vascular leakage in mice, reflecting the pathophysiology of each flavivirus. Mechanistically, each flavivirus NS1 leads to differential disruption of endothelial glycocalyx components, resulting in endothelial hyperpermeability. Our findings reveal the capacity of a secreted viral protein to modulate endothelial barrier function in a tissue-specific manner both in vitro and in vivo, potentially influencing virus dissemination and pathogenesis and providing targets for antiviral therapies and vaccine development.
Topics: Animals; Brain; Cell Line; Cell Membrane Permeability; Dengue; Dengue Virus; Dermis; Encephalitis Virus, Japanese; Endothelial Cells; Gene Expression; Glycocalyx; Humans; Liver; Lung; Male; Mice; Organ Specificity; Primary Cell Culture; Umbilical Veins; Viral Nonstructural Proteins; Virus Replication; West Nile virus; Yellow fever virus; Zika Virus
PubMed: 30726741
DOI: 10.1016/j.celrep.2019.01.036 -
The Lancet. Microbe Sep 2023In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We...
BACKGROUND
In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients.
METHODS
From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor.
FINDINGS
We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation.
INTERPRETATION
This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains.
FUNDING
US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases.
Topics: Humans; Blood Transfusion; Encephalitis; Organ Transplantation; United States; Yellow Fever Vaccine; Yellow fever virus
PubMed: 37544313
DOI: 10.1016/S2666-5247(23)00170-2 -
Journal of Virology Dec 2019The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To...
The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil, we generated 18 complete and nearly complete genomes from the peak of the epidemic curve from nonhuman primates (NHPs) and human infected cases across the Espírito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source, and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic, YFV was reintroduced from Minas Gerais to the Espírito Santo and Rio de Janeiro states multiple times between 2016 and 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce the idea that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in understanding arbovirus epidemics. Arbovirus infections in Brazil, including yellow fever, dengue, zika, and chikungunya, result in considerable morbidity and mortality and are pressing public health concerns. However, our understanding of these outbreaks is hampered by the limited availability of genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak by analyzing genomic data from areas in southeastern Brazil not covered by other previous studies. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from nonhuman primates and infected patients from the southeastern region. Our study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in the field can augment traditional approaches to infectious disease surveillance and control.
Topics: Aedes; Alouatta; Animals; Brazil; Callithrix; Cebus; Disease Outbreaks; Female; Genetic Variation; Genome, Viral; Humans; Incidence; Leontopithecus; Male; Mosquito Vectors; Phylogeny; Phylogeography; Whole Genome Sequencing; Yellow Fever; Yellow fever virus
PubMed: 31597773
DOI: 10.1128/JVI.01623-19 -
Viruses Apr 2017The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well... (Review)
Review
The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus.
Topics: Animals; Disease Models, Animal; Humans; T-Lymphocytes; Yellow Fever Vaccine; Yellow fever virus
PubMed: 28398253
DOI: 10.3390/v9040077 -
PLoS Neglected Tropical Diseases Jan 2019Yellow fever virus (YFV) is a member of the Flaviviridae family. In Brazil, yellow fever (YF) cases have increased dramatically in sylvatic areas neighboring urban zones...
Yellow fever virus (YFV) is a member of the Flaviviridae family. In Brazil, yellow fever (YF) cases have increased dramatically in sylvatic areas neighboring urban zones in the last few years. Because of the high lethality rates associated with infection and absence of any antiviral treatments, it is essential to identify therapeutic options to respond to YFV outbreaks. Repurposing of clinically approved drugs represents the fastest alternative to discover antivirals for public health emergencies. Other Flaviviruses, such as Zika (ZIKV) and dengue (DENV) viruses, are susceptible to sofosbuvir, a clinically approved drug against hepatitis C virus (HCV). Our data showed that sofosbuvir docks onto YFV RNA polymerase using conserved amino acid residues for nucleotide binding. This drug inhibited the replication of both vaccine and wild-type strains of YFV on human hepatoma cells, with EC50 values around 5 μM. Sofosbuvir protected YFV-infected neonatal Swiss mice and adult type I interferon receptor knockout mice (A129-/-) from mortality and weight loss. Because of its safety profile in humans and significant antiviral effects in vitro and in mice, Sofosbuvir may represent a novel therapeutic option for the treatment of YF. Key-words: Yellow fever virus; Yellow fever, antiviral; sofosbuvir.
Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Disease Models, Animal; Drug Resistance, Viral; Hep G2 Cells; Humans; Mice; Mice, Knockout; RNA, Viral; Sofosbuvir; Vero Cells; Yellow Fever; Yellow fever virus
PubMed: 30699122
DOI: 10.1371/journal.pntd.0007072 -
Bis(Benzofuran-1,3-,-heterocycle)s as Symmetric and Synthetic Drug Leads against Yellow Fever Virus.International Journal of Molecular... Oct 2022The yellow fever virus (YFV) is an emerging RNA virus and has caused large outbreaks in Africa and Central and South America. The virus is often transmitted through...
The yellow fever virus (YFV) is an emerging RNA virus and has caused large outbreaks in Africa and Central and South America. The virus is often transmitted through infected mosquitoes and spreads from area to area because of international travel. Being an acute viral hemorrhagic disease, yellow fever can be prevented by an effective, safe, and reliable vaccine, but not be eliminated. Currently, there is no antiviral drug available for its cure. Thus, two series of novel bis(benzofuran−1,3-imidazolidin-4-one)s and bis(benzofuran−1,3-benzimidazole)s were designed and synthesized for the development of anti-YFV lead candidates. Among 23 new bis-conjugated compounds, 4 of them inhibited YFV strain 17D (Stamaril) on Huh-7 cells in the cytopathic effect reduction assays. These conjugates exhibited the most compelling efficacy and selectivity with an EC50 of <3.54 μM and SI of >15.3. The results are valuable for the development of novel antiviral drug leads against emerging diseases.
Topics: Animals; Yellow fever virus; Synthetic Drugs; Yellow Fever Vaccine; Benzofurans; Antiviral Agents; Benzimidazoles
PubMed: 36293531
DOI: 10.3390/ijms232012675 -
Transfusion Mar 2020The reemergence of yellow fever virus (YFV) in Africa and Brazil, and massive vaccine campaigns triggered to contain the outbreaks, have raised concerns over blood...
BACKGROUND
The reemergence of yellow fever virus (YFV) in Africa and Brazil, and massive vaccine campaigns triggered to contain the outbreaks, have raised concerns over blood transfusion safety and availability with increased risk of YFV transfusion-transmitted infections (TTIs) by native and vaccine-acquired YFV. Blood donor deferral for 2 to 4 weeks following live attenuated YFV vaccination, and deferral for travel to endemic/epidemic areas, may result in blood donor loss and impact platelet component (PC) stocks. This study investigated the efficacy of INTERCEPT Blood System pathogen reduction (PR) with use of amotosalen and ultraviolet A (UVA) light to inactivate high levels of YFV in PCs.
MATERIALS
Four units of apheresis platelets prepared in 35% plasma/65% platelet additive solution (PC-PAS) and 4 units of PC in 100% human plasma (PC-Plasma) were spiked with high infectious titers of YFV (YFV-17D vaccine strain). YFV-17D infectious titers were measured by plaque assay and expressed as plaque-forming units (PFU) before and after amotosalen/UVA treatment to determine log reduction.
RESULTS
The mean YFV-17D infectious titers in PC before inactivation were 5.5 ± 0.1 log PFU/mL in PC-PAS and 5.3 ± 0.1 log PFU/mL in PC-Plasma. No infectivity was detected immediately after amotosalen/UVA treatment.
CONCLUSION
The amotosalen/UVA PR system inactivated high titers of infectious YFV-17D in PC. This PR technology could reduce the risk of YFV TTI and help secure PC supplies in areas experiencing YFV outbreaks where massive vaccination campaigns are required.
Topics: Blood Donors; Blood Platelets; Blood Safety; Blood Transfusion; Furocoumarins; Humans; Plateletpheresis; Ultraviolet Rays; Virus Inactivation; Yellow fever virus
PubMed: 31957887
DOI: 10.1111/trf.15673 -
Human Vaccines & Immunotherapeutics Apr 2020Yellow fever has been recently described in nonurban areas of Brazil despite 80 years of commercial vaccine use. Although the disease does not spread fear in the...
Yellow fever has been recently described in nonurban areas of Brazil despite 80 years of commercial vaccine use. Although the disease does not spread fear in the general population as it did in the past, yellow fever virus continues to cause many cases of severe disease. Persistence of the virus in the host is a new mechanism to be considered in the pathology of the disease. Immunization with a fractional dose of vaccine during emergency situations needs to be evaluated for antibody duration, and new and improved vaccines should be considered.
Topics: Brazil; Epidemics; Humans; Vaccination; Yellow Fever; Yellow Fever Vaccine; Yellow fever virus
PubMed: 31634051
DOI: 10.1080/21645515.2019.1678359 -
Journal of Clinical Microbiology Oct 2018Yellow 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... (Review)
Review
Yellow 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.
Topics: Animals; Antibodies, Viral; Diagnostic Tests, Routine; Humans; Molecular Diagnostic Techniques; RNA, Viral; Serologic Tests; Viremia; Yellow Fever; Yellow fever virus
PubMed: 30021822
DOI: 10.1128/JCM.00827-18