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Histone acetyltransferases and N-terminal acetyltransferases orchestrate development and metamorphosis in the yellow fever mosquito, Aedes aegypti.

Mosquitoes, especially Aedes aegypti, transmit major human diseases such as dengue, Zika, and chikungunya. Epigenetic regulation, including histone acetylation, plays a key role in controlling Ae. aegypti development. However, the specific roles of histone acetyltransferases (HATs) and N-terminal acetyltransferases (NATs) in mosquito development remain poorly understood. In this study, we investigated 25 HAT/NAT genes functions by knocking them down via feeding Ae. aegypti larvae with dsRNA nanoformulations. Gene expression analysis confirmed that target gene expression was reduced by more tha

Interferon-induced activation of dendritic cells and monocytes by yellow fever vaccination correlates with early antibody responses.

Yellow fever vaccination provides long-lasting protection and is a unique model for studying the immune response to an acute RNA virus infection in humans. To elucidate the early innate immune events preceding the rapid generation of protective immunity, we performed transcriptome analysis of human blood dendritic cell (DC) and monocyte subpopulations before and 3, 7, 14, and 28 d after vaccination. We detected temporary upregulation of IFN-stimulated genes (ISG) in all DC and monocyte subsets on days 3 and 7 after vaccination as well as cell type-specific responses and response kinetics. Sing…

Investigating the association between yellow fever vaccination and symptomatic acute Zika virus infection: a case-control study.

BACKGROUND: During the Zika virus (ZIKV) epidemic in Latin America (2015-2016), a high incidence of microcephaly was observed in places with low yellow fever (YF) vaccination coverage. Cross-reactivity between ZIKV and YF virus was hypothesized as a possible explanation. METHODS: We performed a case-control study to estimate the odds of ZIKV infection according to patients' YF vaccination status. The study considered ZIKV fever as the outcome, and previous vaccination against YF as exposure. We included all confirmed cases of acute ZIKV fever in Campo Grande, Mato Grosso do Sul, from January …

Расширенный диапазон Haemagogus leucocelaenus в горячих точках желтой лихорадки: новые данные из штата Санта-Катарина, южная Бразилия.

В род Haemagogus входят девять видов комаров, о которых сообщается в Бразилии, причем каждая из них имеет разную структуру распределения. Хемагогус лейкоцелаен, крупный вектор желтой лихорадки, широко распространен по всей стране, в то время как Haemagogus leucophoebus, морфологически похожий вид, был обнаружен только в штате Акре. ЦЕЛИ: В этом исследовании была проведена оценка присутствия видов гемагога в южной части Бразилии путем сопоставления их морфологических и молекулярных характеристик. МЕТОДЫ: Москито были собраны в пяти муниципалитетах штата Санта-Катарина, Бразилия. Каждый образец

Совпадение в аннотации оригинала
BACKGROUND: The Haemagogus genus includes nine mosquito species reported in Brazil, each with distinct distribution patterns. Haemagogus leucocelaenus, a major yellow fever vector, is widely distributed throughout the country, while Haemagogus leucophoebus, a morphologically similar species, has only been identified in Acre State. OBJECTIVES: This study eva…

Yellow Fever Virus Interactomes Reveal Common and Divergent Strategies of Replication and Evolution for Mosquito-borne Flaviviruses.

Pathogenic mosquito-borne flaviviruses infect mosquito and human hosts, relying on host protein interactions to replicate, evade immunity, and mediate pathogenesis. Prior proteomic studies mapped such interactions for some flaviviruses, but yellow fever virus (YFV)-a pathogen of resurgent concern-remains understudied. Here, we map YFV interactomes in human and mosquito cells to identify interactions common among divergent flaviviruses or unique to YFV. Functional assays reveal a previously unrecognized YFV restriction factor: RBBP6 inhibits YFV genome replication by interacting with the viral …

Odorant receptors for floral- and plant-derived volatiles in the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae).

Adult mosquitoes require regular sugar meals, usually floral nectar, to survive and flourish in natural habitats. Both males and females locate potential sugar sources using sensory proteins called odorant receptors activated by plant volatiles that facilitate orientation toward flowers or honeydew. The Yellow Fever mosquito, Aedes aegypti (Linnaeus, 1762), possesses a large repertoire of odorant receptors, many of which are likely to support floral odor detection and nectar-seeking. In this study, we have employed a heterologous expression system and the two-electrode voltage clamping techniq…

Differentiation marker-negative CD4+ T cells persist after yellow fever virus vaccination and contribute to durable memory.

Factors that contribute to durable immunological memory remain incompletely understood. In our longitudinal analyses of CD4+ T cell responses to the yellow fever virus (YFV) vaccine by peptide-MHC tetramers, we unexpectedly found naïve phenotype virus-specific CD4+ T cells that persisted months to years after immunization. These Marker negative T cells (TMN) lacked CD95, CXCR3, CD11a, and CD49d surface protein expression, distinguishing them from previously discovered stem-cell memory T cells. Functionally, they resembled genuine naïve T cells upon in vitro stimulation. Single-cell TCR sequenc…

Odorant receptors for floral- and plant-derived volatiles in the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae).

Adult mosquitoes require regular sugar meals, including nectar, to survive in natural habitats. Both males and females locate potential sugar sources using sensory proteins called odorant receptors (ORs) activated by plant volatiles to orient toward flowers or honeydew. The yellow fever mosquito, Aedes aegypti (Linnaeus, 1762), possesses a large gene family of ORs, many of which are likely to detect floral odors. In this study, we have uncovered ligand-receptor pairings for a suite of Aedes aegypti ORs using a panel of environmentally relevant, plant-derived volatile chemicals and a heterologo…

Optimization of process parameters for specific pathogen-free chicken embryonic fibroblast cultivation for yellow fever vaccine production.

The yellow fever (YF) vaccine is usually produced with egg-based methods, which has limitations, including potential adverse effects and low production yields. Alternatively, producing the vaccine using Vero cells or HEK 293 cells can overcome some of these issues, but these methods are significantly more expensive. In the current study, the YF vaccine candidate 17DD virus was produced in primary chicken embryo fibroblast (CEF) cells. The primary CEF cells isolation from eggs was optimized through a two-step process. In the first step, the important parameters that contribute to the developmen…

Knowledge, attitudes and practice questionnaires in dengue, Zika, chikungunya and yellow fever settings: a scoping review protocol.

INTRODUCTION: Arboviruses are a broad classification of viral pathogens that require vectors such as mosquitoes for infection transmission. The burden of arboviral diseases worldwide is substantial, affecting millions of people annually, with the Aedes aegypti mosquito responsible for spreading several common arboviruses, including dengue, chikungunya, Zika and yellow fever. One public health strategy to control and prevent these viruses is to influence community members' behaviours related to reducing the breeding sites of Aedes mosquitoes, and knowledge, attitudes and practice (KAP) question…

Evaluation of Yellow Fever Virus Infection in Aedes aegypti Mosquitoes from Pakistan with Distinct Knockdown Resistance Genotypes.

BACKGROUND: Yellow fever (YF) is an acute hemorrhagic disease endemic to Africa and Latin America; however, no cases have been reported in Asian regions with high Aedes aegypti infestation. Factors such as environmental conditions and genetic variations in the yellow fever virus (YFV) strains and mosquito populations may explain this absence. Mosquito populations have undergone strong selective pressure owing to the excessive use of insecticides. This pressure has led to the spread of alterations, such as knockdown-resistant mutations (kdr), which, while conferring resistance to pyrethroids, a…

New insight into flavivirus maturation from structure/function studies of the yellow fever virus envelope protein complex.

All enveloped viruses enter cells by fusing their envelope with a target cell membrane while avoiding premature fusion with membranes of the … pH only after their release into the neutral pH extracellular environment. Our study shows that for yellow fever virus (YFV), the mechanism of activation involves actively knocking out the fusion brake (protein pr) through a localized conformational change of the envelope protein upon exposure to the neutral pH external environment. Our study has important imp …

Genetic Structuring of One of the Main Vectors of Sylvatic Yellow Fever: Haemagogus (Conopostegus) leucocelaenus (Diptera: Culicidae).

Genetic diversity and population structuring for the species Haemogogus leucocelaenus, a sylvatic vector of yellow fever virus, were found to vary with the degree of agricultural land use and isolation of fragments of Atlantic Forest in municipalities in the state of São Paulo where specimens were collected. Genotyping of 115 mitochondrial SNPs showed that the populations with the highest indices of genetic diversity (polymorphic loci and mean pairwise differences between the sequences) are found in areas with high levels of agricultural land use (northeast of the State). Most populations exhi…

Genotype-specific features reduce the susceptibility of South American yellow fever virus strains to vaccine-induced antibodies.

The resurgence of yellow fever in South America has prompted vaccination against the etiologic agent, yellow fever virus (YFV). Current vaccines are based on a live-attenuated YF-17D virus derived from a virulent African isolate. The capacity of these vaccines to induce neutralizing antibodies against the vaccine strain is used as a surrogate for protection. However, the sensitivity of genetically distinct South American strains to vaccine-induced antibodies is unknown. We show that antiviral potency of the polyclonal antibody response in vaccinees is attenuated against an emergent Brazilian s…

Biological Characterization of Yellow Fever Viruses Isolated From Non-human Primates in Brazil With Distinct Genomic Landscapes.

Since the beginning of the XXI Century, the yellow fever virus (YFV) has been cyclically spreading from the Amazon basin to Brazil's South and Southeast regions, culminating in an unprecedented outbreak that started in 2016. In this work, we studied four YFV isolated from non-human primates obtained during outbreaks in the states of Rio Grande do Sul in 2008 (PR4408), Goiás (GO05), and Espírito Santo (ES-504) in 2017, and Rio de Janeiro (RJ 155) in 2019. These isolates have genomic differences mainly distributed in non-structural proteins. We compared the isolates' rates of infection in mammal…

Juvenile hormone-induced histone deacetylase 3 suppresses apoptosis to maintain larval midgut in the yellow fever mosquito.

SignificanceJuvenile hormone (JH), a sesquiterpenoid, regulates many aspects of insect development, including maintenance of the larval stage by preventing metamorphosis. In contrast, ecdysteroids promote metamorphosis by inducing the E93 transcription factor, which triggers apoptosis of larval cells and remodeling of the larval midgut. We discovered that JH suppresses precocious larval midgut-remodeling by inducing an epigenetic modifier, histone deacetylase 3 (HDAC3). JH-induced HDAC3 deacetylates the histone H4 localized at the promoters of proapoptotic genes, resulting in the suppression o

Bis(Benzofuran-1,3-N,N-heterocycle)s as Symmetric and Synthetic Drug Leads against Yellow Fever Virus.

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 develop…