Biology subjects

Koenraadt, C. J. M.

Publications and source records attributed to Koenraadt, C. J. M..

12 recordsLinked to original sources

bioRxiv2025

Green cities and the risk for vector-borne disease transmission for humans and animals: a scoping review

BackgroundGreening cities is a nature-based strategy for sustainable urban development that integrates natural elements like plants or water bodies, to mitigate climate change impacts and enhance human well-being. However, urban green infrastructures (UGIs) can influence the distribution of disease vectors, potentially affecting vector-borne diseases (VBDs). UGIs may provide new suitable environments for urban vectors, while also creating opportunities to mitigate VBD risks through predation, competition, and dilution effects. This article examined the relationships between UGIs, vectors, and associated pathogens, impacting both human and animal health, highlighting knowledge gaps and identifying research priorities to support VBD risk mitigation measures and to guide smart urban planning and design. MethodsA systematic literature search was conducted following PRISMA guidelines in three databases (Pubmed, Scopus, Web of Science). Selected articles involved (i) any aspect of a urban vector system, (ii) in UGIs, and (iii) statistical analysis of the effects of UGIs on VBD risk. Methods employed to characterize UGIs and VBDs were described and the identified impacts were summarized by vector group. ResultsAmong the 98 articles reviewed, most addressed mosquito-pathogen systems (66), tick-pathogen systems (29), and few other vector-borne pathogen systems (3), with studies often confined to a single city or several cities within the same country and focused on one vector group. Urban vegetation generally appeared to heighten the risk of tick-borne diseases. In contrast, the influence of UGIs on the risk of mosquito-borne diseases varied depending on the vector system and on the environmental and climatic context. The diversity of indicators used to assess UGIs and VBD risks may affect the observed impact on VBD risk. ConclusionGiven the increasing popularity of urban greening, it is crucial to investigate its potential implications for public health, and thereby urban planning decisions. However, the lack of standardized protocols complicates the accurate assessment of the effects of UGIs on the risk for VBD emergence and transmission and consequently, on potential mitigation measures.

ecology↗

bioRxiv2024

Emergence and Dynamics of Usutu and West Nile Viruses in the Netherlands, 2016-2022

BackgroundMosquito-borne arboviruses, including Usutu virus (USUV) and West Nile virus (WNV), are emerging threats in Europe, with changes in climate, land use, and increased travel and trade influencing their dynamics. Understanding the emergence and establishment of these viruses in new regions is critical for informing targeted mitigation of drivers of emergence and enhancing public and wildlife health preparedness. MethodsSeven years (2016-2022) of interconnected studies were conducted in the Netherlands. Live birds were sampled by volunteer bird ringers, dead birds were referred for sampling by citizen-scientists and zoological institutions, and mosquitoes were trapped. Samples were tested for USUV and WNV using RT-PCR and screened for Orthoflavivirus antibodies using protein microarray and neutralization assays. Sequencing and phylogenetic analyses were performed. FindingsUSUV was first detected in the Netherlands in 2016, caused large outbreaks in birds until 2018, and resurged in 2022. One dominant, enzootic lineage, co-circulated alongside several limited introductions of a second lineage. A localized WNV lineage 2 outbreak occurred in live birds and mosquitoes in 2020, with another positive bird in 2022 and serological evidence of continued circulation. InterpretationWe provide the first comprehensive, multi-year documentation of two emerging arboviruses in the Netherlands. USUV was enzootically maintained over seven years and was associated with substantial bird mortality. WNV is in an early stage of establishment with no bird mortality observed. Our integrated wildlife sampling was crucial in detecting a human WNV outbreak, bringing this emerging threat to public health attention. FundingZonMw, Dutch Research Council (NWO), European Union, Government of the Netherlands

microbiology↗

bioRxiv2024

The piRNA pathway mediates transcriptional silencing of LTR retrotransposons in the soma and germline of Aedes mosquitoes

The PIWI-interacting RNA (piRNA) pathway preserves genomic integrity by suppressing transposable elements in animal germlines. Despite its well-established function in the animal germline, piRNAs and PIWI proteins are expressed in somatic tissues across arthropod species, and their functions outside the gonads remain poorly understood. Aedes albopictus mosquitoes express four PIWI genes, Piwi4, Piwi5, Piwi6 and Ago3, in both gonadal and somatic tissues. Here, we generated Piwi6 knockout Ae. albopictus cell lines and observed a substantial upregulation of Long Terminal Repeat (LTR)-retrotransposons, including a full-length endogenous retrovirus that we named AalERV1. Nascent RNA-sequencing and CUT&Tag analyses revealed that Piwi6 silences AalERV1 transcriptionally by guiding the deposition of the repressive H3K9me3 histone mark. Consistently, Piwi6 localized to both the cytoplasm and nucleus, with sequences in the intrinsically disordered region guiding nuclear translocation. Reintroduction of full-length GFP-Piwi6, but not a mutant GFP-Piwi6 defective in nuclear localization, rescued AalERV1 derepression in Piwi6 knockout cells. Importantly, the control of AalERV1 was recapitulated in vivo as Piwi6 knockdown increased AalERV1 expression in both ovaries and somatic tissues of Ae. albopictus mosquitoes. These results establish Aedes mosquitoes as a model to study nuclear PIWI functions and suggest that somatic piRNA-mediated transposon silencing is evolutionarily conserved across arthropod species.

molecular biology↗

bioRxiv2024

Biological tick control: modeling the potential impact of entomopathogenic fungi on the transmission of East Coast fever in cattle

Biological control of ticks using entomopathogenic fungi (EPF) is a highly desired alternative to chemical acaricides for the control of tick-borne pathogens. For Metarhizium anisopliae isolate ICIPE 7, one of these EPFs, efficacy against multiple tick species has been demonstrated in laboratory and field settings. However, we currently have little quantitative understanding of how EPFs can impact transmission. We developed a deterministic model of tick-host-pathogen interactions to explore how the effects of EPF on Rhipicephalus appendiculatus ticks may impact the transmission dynamics of East Coast fever (ECF) in cattle populations. We parameterized the multi-faceted effects of EPFs on tick dynamics using experimental data on Tickoff(R) biopesticide (a novel formulation of M. anisopliae ICIPE 7) and related EPFs. The epidemiological impact of EPF was evaluated across a range of product profiles and implementation strategies. Model results indicate that, for the explored product profiles, EPF derives most of its epidemiological impact through the delayed mortality effect. This EPF-induced mortality could not only reduce the onward Theileria parva transmission to cattle (both treated and untreated) but could also cause a reduction in the tick-to-host ratio and thus cattle exposure to ticks. The effects of EPF on reproduction fitness and engorgement of ticks elicit negligible impact. High levels of population coverage and treatment frequency are needed to reduce the tick population size and reach meaningful epidemiological impact in cattle populations. Additionally, increasing the persistence time of fungal conidia on cattle skin - through technological improvements to the EPF formulation - can substantially reduce acute infections when combined with appreciable population coverage levels, treatment frequency, and efficient spraying techniques. Our model analysis provides insights into the potential impact of EPF when deployed at a population level, and lends support to further research and development of this biological tick control tool.

microbiology↗

bioRxiv2023

Quantifying Rift Valley fever virus transmission efficiency in a lamb-mosquito-lamb model

Rift Valley fever virus (RVFV) is a (re)emerging mosquito-borne pathogen impacting human and animal health. How RVFV spreads through a population depends on population-level interactions between hosts and vectors (e.g., vector-to-host ratio and biting preference) and also on potential differences in individual following virus exposure (e.g., transmission efficiencies from host to vector and vice versa). Here, we estimated the probability for RVFV to transmit to naive animals by experimentally exposing lambs to a bite of an infectious mosquito (the transmission efficiency) and assessed if and how RVFV infection subsequently developed in the exposed animal. Aedes aegypti mosquitoes, previously infected via feeding on a viremic lamb, were used to expose naive lambs to the virus. Lambs were either exposed to 1-3 (low exposure) or 7-9 (high exposure) infectious mosquitoes. All lambs in the high exposure group became viremic and showed characteristic signs of Rift Valley fever within 2-4 days post exposure. In contrast, 3 out of 12 lambs in the low exposure group developed viremia and disease, with similar peaks in viremia as the high exposure group but with some heterogeneity in the onset of viremia. These results suggest that the likelihood for successful infection of a ruminant host is affected by the number of infectious mosquitoes biting, but also highlights that a lamb can be infected by a single mosquito. The per bite mosquito-to-host transmission efficiency was estimated at 28% (95% confidence interval: 15 - 47%). We subsequently combined this transmission efficiency with estimates for mosquito life traits into a Ross-McDonald mathematical model to illustrate scenarios under which major RVFV outbreaks could occur in naive populations (i.e., R0 >1). The model revealed that for efficient RVFV transmission relatively high vector-to-host ratios as well as strong feeding preference for competent hosts are required. Altogether, this study highlights the importance of experiments that mimic natural exposure to RVFV. The experiments facilitate a better understanding of the natural progression of disease and a direct way to obtain epidemiological parameters for mathematical models.

microbiology↗

bioRxiv2023

Phase Separation and Ageing of Glycine-Rich Protein from Tick Adhesive

Hard ticks feed on their host for multiple days. To ensure firm attachment, they secrete a protein-rich saliva that eventually forms a solid cement cone. The underlying mechanism of this liquid-to-solid transition is not yet understood. This study focuses on the phase transitions of a disordered glycine-rich protein (GRP) that is prominent in tick saliva. We show that GRP undergoes liquid-liquid phase separation via simple coacervation to form biomolecular condensates in salty environments. Cation-pi and pi-pi interactions near the C-terminus promote coacervation while a negatively charged N-terminus prolongs its onset through electrostatic repulsion. Interestingly, GRP condensates exhibit ageing and undergo liquid-to-gel transition to form viscoelastic networks as well as solid-like condensates. Lastly, we provide evidence for protein-rich condensates in natural tick saliva. Our findings provide a starting point to gain insights into the bioadhesion of ticks, develop novel tick control strategies, and towards biomedical applications such as tissue sealants.

biochemistry↗

bioRxiv2022

The virome of the invasive Asian bush mosquito Aedes japonicus in Europe

BackgroundThe Asian bush mosquito Aedes japonicus is rapidly invading North America and Europe. Due to its potential to transmit multiple pathogenic arthropod-borne (arbo)viruses including Zika virus, West Nile virus and chikungunya virus, it is important to understand the biology of this vector mosquito in more detail. In addition to arboviruses, mosquitoes can also carry insect-specific viruses that receive increasing attention due to their potential effects on host physiology and arbovirus transmission. In this study, we characterized the collection of viruses, referred to as the virome, circulating in Ae. japonicus populations in the Netherlands and France. ResultsApplying a small RNA-based metagenomic approach to Ae. japonicus, we uncovered a distinct group of viruses present in samples from both the Netherlands and France. These included one known virus, Ae. japonicus narnavirus 1 (AejapNV1), and three new virus species that we named Ae. japonicus totivirus 1 (AejapTV1), Ae. japonicus anphevirus 1 (AejapAV1) and Ae. japonicus bunyavirus 1 (AejapBV1). We also discovered sequences that were presumably derived from two additional novel viruses: Ae. japonicus bunyavirus 2 (AejapBV2) and Ae. japonicus rhabdovirus 1 (AejapRV1). All six viruses induced strong RNA interference responses, including the production of 21 nucleotide sized small interfering RNAs, a signature of active replication in the host. Notably, AejapBV1 and AejapBV2 belong to different viral families, however, no RNA-dependent RNA polymerase sequence has been found for AejapBV2. Intriguingly, our small RNA-based approach identified a [~]1 kb long ambigrammatic RNA that is associated with AejapNV1 as a secondary segment but showed no similarity to any sequence in public databases. We confirmed the presence of AejapNV1 primary and secondary segments, AejapTV1, AejapAV1 and AejapBV1 by reverse-transcriptase PCR in wild-caught Ae. japonicus mosquitoes. AejapNV1 and AejapTV1 were found at high prevalence (87-100%) in adult females, adult males and larvae. ConclusionsUsing a small RNA-based, sequence-independent metagenomic strategy, we uncovered a conserved and prevalent virome among Ae. japonicus mosquito populations. The high prevalence of AejapNV1 and AejapTV1 across all tested mosquito life stages suggests that these viruses are intimately associated with Ae. japonicus and may affect different aspects of the physiology of this vector mosquito.

microbiology↗

bioRxiv2022

Incomplete bunyavirus particles contribute to within-host spread and between-host transmission

Bunyaviruses lack a specific mechanism to ensure the incorporation of a complete set of genome segments into each virion, explaining the generation of incomplete virus particles lacking one or more genome segments. Such incomplete virus particles, which may represent the majority of particles produced, are generally considered to interfere with virus infection and spread. Using the three-segmented Rift Valley fever virus as a model bunyavirus, we here show that two distinct incomplete virus particle populations that are unable to spread autonomously, are able to efficiently complement each other in both mammalian and insect cells following co-infection. We further show that incomplete virus particles are capable of co-infecting mosquitoes, resulting in the rescue of infectious virus that is able to disseminate to the mosquito salivary glands. Our findings reveal a significant role of incomplete particles in within-host spread and between-host transmission, reminiscent of the life cycle of multipartite viruses.

microbiology↗

bioRxiv2021

dynamAedes: a unified modelling framework for invasive Aedes mosquitoes

O_LIMosquito species belonging to the genus Aedes have attracted the interest of scientists and public health officers for their invasive species traits and efficient capacity of transmitting viruses affecting humans. Some of these species were brought outside their native range by human activities such as trade and tourism, and colonised new regions thanks to a unique combination of eco-physiological traits. C_LIO_LIConsidering mosquito physiological and behavioural traits to understand and predict the spatial and temporal population dynamics is thus a crucial step to develop strategies to mitigate the local densities of invasive Aedes populations. C_LIO_LIHere, we synthesised the life cycle of four invasive Aedes species (Ae. aegypti, Ae. albopictus, Ae. japonicus and Ae. koreicus) in a single multi-scale stochastic modelling framework which we coded in the R package dynamAedes. We designed a stage-based and time-discrete stochastic model driven by temperature, photo-period and inter-specific larval competition that can be applied to three different spatial scales: punctual, local and regional. These spatial scales consider different degrees of spatial complexity and data availability, by accounting for both active and passive dispersal of mosquito species as well as for the heterogeneity of the input temperature data. C_LIO_LIOur overarching aim was to provide a flexible, open-source and user-friendly tool rooted in the most updated knowledge on species biology which could be applied to the management of invasive Aedes populations as well as for more theoretical ecological inquiries. C_LI

ecology↗

bioRxiv2021

Insect-specific viruses regulate vector competence in Aedes aegypti mosquitoes via expression of histone H4

Aedes aegypti and Aedes albopictus are major mosquito vectors for arthropod-borne viruses (arboviruses) such as dengue (DENV) and Zika (ZIKV) viruses. Mosquitoes also carry insect-specific viruses (ISVs) that may affect the transmission of arboviruses. Here, we analyzed the global virome in urban Aedes mosquitoes and observed that two insect-specific viruses, Phasi Charoen-like virus (PCLV) and Humaita Tubiacanga virus (HTV), were the most prevalent in A. aegypti worldwide except for African cities, where transmission of arboviruses is low. Spatiotemporal analysis revealed that presence of HTV and PCLV led to a 200% increase in the chances of having DENV in wild mosquitoes. In the laboratory, we showed that HTV and PCLV prevented downregulation of histone H4, a previously unrecognized proviral host factor, and rendered mosquitoes more susceptible to DENV and ZIKV. Altogether, our data reveals a molecular basis for the regulation of A. aegypti vector competence by highly prevalent ISVs that may impact how we analyze the risk of arbovirus outbreaks.

microbiology↗

bioRxiv2021

An adaptive compromise - Conflicting evolutionary pressures on arthropod borne Zika virus dinucleotide composition in mammalian hosts and mosquito vectors

Most vertebrate RNA viruses show pervasive suppression of CpG and UpA dinucleotides, closely resembling the dinucleotide composition of host cell transcriptomes. In contrast, CpG suppression is absent in both invertebrate mRNA and RNA viruses that exclusively infect arthropods. Arthropod-borne (arbo) viruses are transmitted between vertebrate hosts by invertebrate vectors and thus encounter potentially conflicting evolutionary pressures in the different cytoplasmic environments. Using a newly developed Zika virus (ZIKV) model, we have investigated how demands for CpG suppression in vertebrate cells can be reconciled with potentially quite different compositional requirements in invertebrates, and how this affects ZIKV replication and transmission. Mutant viruses with synonymously elevated CpG or UpA dinucleotide frequencies showed attenuated replication in vertebrate cell lines, which was rescued by knockout of the zinc-finger antiviral protein (ZAP). Conversely, in mosquito cells, ZIKV mutants with elevated CpG dinucleotide frequencies showed substantially enhanced replication compared to wildtype. Host-driven effects on virus replication attenuation and enhancement were even more apparent in mouse and mosquito models. Infections with CpG-or UpA-high ZIKV mutants in mice did not cause typical ZIKV-induced tissue damage and completely protected mice during subsequent challenge with wildtype virus, which demonstrates their potential as live-attenuated vaccines. In contrast, the CpG-high mutants displayed enhanced replication in Aedes aegypti mosquitoes and a larger proportion of mosquitoes carried infectious virus in their saliva. These findings show that mosquito cells are also capable of discriminating RNA based on dinucleotide composition. However, the evolutionary pressure on the CpG dinucleotides of viral genomes in arthropod vectors directly opposes the pressure present in vertebrate host cells, which provides evidence that an adaptive compromise is required for arbovirus transmission. This suggests that the genome composition of arthropod-borne flaviviruses is crucial to maintain the balance between high-level replication in the vertebrate host and persistent replication in the mosquito vector.

microbiology↗

bioRxiv2019

A new high-throughput tool to screen mosquito-borne viruses in Zika virus endemic/epidemic areas

Mosquitoes are vectors of arboviruses affecting animal and human health. Arboviruses circulate primarily within an enzootic cycle and recurrent spillovers contribute to the emergence of human-adapted viruses able to initiate an urban cycle involving anthropophilic mosquitoes. The increasing volume of travel and trade offers multiple opportunities for arbovirus introduction in new regions. This scenario has been exemplified recently with the Zika pandemic. To incriminate a mosquito as vector of a pathogen, several criteria are required such as the detection of natural infections in mosquitoes. In this study, we used a high-throughput chip based on the BioMarkTM Dynamic arrays system capable of detecting 64 arboviruses in a single experiment. A total of 17,958 mosquitoes collected in Zika-endemic/epidemic countries (Brazil, French Guiana, Guadeloupe, Suriname, Senegal, and Cambodia) were analyzed. Here we show that this new tool can detect endemic and epidemic viruses in different mosquito species in an epidemic context. Thus, this fast and low-cost method can be suggested as a novel epidemiological surveillance tool to identify circulating arboviruses.

molecular biology↗