Ronald P van Rij

Ronald P van Rij
Radboud University Medical Centre (Radboudumc) · Medical Microbiology

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177
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Introduction
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Publications

Publications (177)
Article
Full-text available
Knowledge about contagiousness is key to accurate management of hospitalized COVID-19 patients. Epidemiological studies suggest that in addition to transmission through droplets, aerogenic SARS-CoV-2 transmission contributes to the spread of infection. However, the presence of virus in exhaled air has not yet been sufficiently demonstrated. In pand...
Article
Full-text available
Dengue is an important arboviral infectious disease for which there is currently no specific cure. We report gemini-like (geminoid) alkylated amphiphilic peptides containing lysines in combination with glycines or alanines (C15H31C(O)-Lys-(Gly or Ala)nLys-NHC16H33, shorthand notation C16-KXnK-C16 with X = A or G, and n = 0-2). The representatives w...
Article
After decades of being considered non-pathogenic, Zika virus (ZIKV) emerged as an important threat to human health during the epidemic of 2015–2016. ZIKV infections are usually asymptomatic, but can cause Guillain-Barré syndrome in adults and microcephaly in newborns. As there are currently no approved antiviral drugs against ZIKV, we tested anti-Z...
Preprint
Efficient virus replication in Aedes vector mosquitoes is essential for the transmission of arboviral diseases such as dengue virus (DENV) in human populations. Like in vertebrates, virus-host protein-protein interactions are essential for viral replication and immune evasion in the mosquito vector. Here, 79 mosquito host proteins interacting with...
Article
Full-text available
Background Endothelial hyper-permeability with plasma leakage and thrombocytopenia are predominant features of severe dengue virus infection. It is well established that heparanase, the endothelial glycocalyx degrading enzyme, plays a major role in various diseases with vascular leakage. It is yet to be elucidated whether heparanase activity plays...
Article
Full-text available
Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney indepe...
Article
Repurposing drugs is a promising strategy to identify therapeutic interventions against novel and re-emerging viruses. Posaconazole is an antifungal drug used to treat invasive aspergillosis and candidiasis. Recently, posaconazole and its structural analog, itraconazole were shown to inhibit replication of multiple viruses by modifying intracellula...
Article
Background: Prolonged SARS-CoV-2 shedding has been described in immunocompromised COVID-19 patients, resulting in protracted disease and poor outcome. Specific therapy to improve viral clearance and outcome for this group of patients is currently unavailable. Methods: Five critically ill COVID-19 patients with severe defects in cellular immune r...
Article
Full-text available
In the germline of animals, PIWI interacting (pi)RNAs protect the genome against the detrimental effects of transposon mobilization. In Drosophila, piRNA-mediated cleavage of transposon RNA triggers the production of responder piRNAs via ping-pong amplification. Responder piRNA 3′ end formation by the nuclease Zucchini is coupled to the production...
Article
PIWI-interacting (pi)RNAs are small silencing RNAs that are crucial for the defense against transposable elements in germline tissues of animals. In Aedes aegypti mosquitoes, the piRNA pathway also contributes to gene regulation in somatic tissues, illustrating additional roles for piRNAs and PIWI proteins besides transposon repression. Here, we id...
Article
Small RNAs are crucial for the regulation of basic cellular processes and protection against viruses and transposons in mosquitoes. Rozen-Gagnon et al. established CLIP (cross-linking and immunoprecipitation) for Argonaute proteins in Aedes aegypti. Their study sheds light on small RNA–target interactions in mosquitoes and provides an important res...
Preprint
Full-text available
The mRNA-based BNT162b2 vaccine from Pfizer/BioNTech was the first registered COVID-19 vaccine and has been shown to be up to 95% effective in preventing SARS-CoV-2 infections. Little is known about the broad effects of the new class of mRNA vaccines, especially whether they have combined effects on innate and adaptive immune responses. Here we con...
Article
Full-text available
As in most arthropods, the PIWI-interacting RNA (piRNA) pathway in the vector mosquito Aedes aegypti is active in diverse biological processes in both soma and germline. To gain insights into piRNA biogenesis and effector complexes, we mapped the interactomes of the somatic PIWI proteins Ago3, Piwi4, Piwi5, and Piwi6 and identify numerous specific...
Article
Full-text available
Neutrophil extracellular traps (NETs) are increasingly recognized to play a role in the pathogenesis of viral infections, including dengue. NETs can be formed NADPH oxidase (NOX)-dependently or NOX-independently. NOX-independent NETs can be induced by activated platelets and are very potent in activating the endothelium. Platelet activation with th...
Article
Full-text available
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two...
Article
Full-text available
Horizontal gene transfer from viruses to eukaryotic cells is a pervasive phenomenon. Somatic viral integrations are linked to persistent viral infection whereas integrations into germline cells are maintained in host genomes by vertical transmission and may be co-opted for host functions. In the arboviral vector Aedes aegypti, an endogenous viral e...
Preprint
Full-text available
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and has infected an estimated 10% of the global population in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures including vaccines. In this study, we demonstrate that berberine and o...
Article
Full-text available
Background: The Asian tiger mosquito Aedes albopictus is globally expanding and has become the main vector for human arboviruses in Europe. With limited antiviral drugs and vaccines available, vector control is the primary approach to prevent mosquito-borne diseases. A reliable and accurate DNA sequence of the Ae. albopictus genome is essential to...
Preprint
Full-text available
PIWI interacting (pi)RNAs are small RNAs mostly known to protect the genomes of animal germlines against transposable elements. In Drosophila , piRNA-mediated cleavage of transposon RNA triggers the release of a responder piRNAs via the ping-pong amplification cycle. Responder piRNA 3` end formation by the endonuclease Zucchini is coupled to the pr...
Article
Full-text available
Endogenous viral elements (EVEs) are viral sequences integrated in host genomes. A large number of non-retroviral EVEs was recently detected in Aedes mosquito genomes, leading to the hypothesis that mosquito EVEs may control exogenous infections by closely related viruses. Here, we experimentally investigated the role of an EVE naturally found in A...
Article
RNA interference (RNAi) is a powerful host defense mechanism against viruses. As a counter-defense, many viruses encode suppressors of RNAi, which – in plants – has provoked counter-counter-defense strategies. Recently, a mechanism was proposed in Drosophila (Zhang et al.) wherein a long noncoding RNA senses a virus-encoded RNAi suppressor to activ...
Chapter
The phenotypic manifestations of disease induced by viruses and subviral infectious entities are the result of complex molecular interactions between host and viral factors. The viral determinants of the diseased phenotype have traditionally been sought at the level of structural or non-structural proteins. However, the discovery of RNA silencing m...
Preprint
Full-text available
In the model organism Drosophila melanogaster, the PIWI-interacing RNA pathway contributes in silencing transposable elements (TEs) through smallRNAs (piRNAs), which arise from genomic loci (piRNA clusters) that contain sequences of previously-acquired TEs. As such, they are a functionally-immune archive of previous TE invasions that is passed to t...
Article
Full-text available
Tandem repeat elements such as the diverse class of satellite repeats occupy large parts of eukaryotic chromosomes, mostly at centromeric, pericentromeric, telomeric and subtelomeric regions¹. However, some elements are located in euchromatic regions throughout the genome and have been hypothesized to regulate gene expression in cis by modulating l...
Preprint
Full-text available
Endogenous viral elements (EVEs) are viral sequences integrated in host genomes. A large number of non-retroviral EVEs was recently detected in Aedes mosquito genomes, leading to the hypothesis that mosquito EVEs may control exogenous infections by closely related viruses. Here, we experimentally investigated the role of an EVE naturally found in A...
Preprint
Full-text available
PIWI-interacting (pi)RNAs are small silencing RNAs that are crucial for the defense against transposable elements in germline tissues of animals. In the mosquito (i)Aedes aegypti(/i), the piRNA pathway also contributes to gene regulation in somatic tissues, illustrating additional roles for piRNAs and PIWI proteins besides transposon repression. He...
Preprint
Full-text available
The Asian tiger mosquito Aedes albopictus is globally expanding and has become the main vector for human arboviruses in Europe. Here we present AalbF2, a dramatically improved assembly of the Ae. albopictus genome that has revealed widespread viral insertions, novel microRNAs and piRNA clusters, the sex determining locus, new immunity genes, and ha...
Preprint
Full-text available
Tandem repeat elements such as the highly diverse class of satellite repeats occupy large parts of eukaryotic chromosomes. Most occur at (peri)centromeric and (sub)telomeric regions and have been implicated in chromosome organization, stabilization, and segregation. Others are located more dispersed throughout the genome, but their functions remain...
Article
Coevolution of viruses and their hosts may lead to viral strategies to avoid, evade, or suppress antiviral immunity. An example is antiviral RNA interference (RNAi) in insects: the host RNAi machinery processes viral double-stranded RNA into small interfering RNAs (siRNAs) to suppress viral replication, whereas insect viruses encode suppressors of...
Article
Full-text available
The genus Alphavirus harbours mostly insect-transmitted viruses that cause severe disease in humans, livestock and wildlife. Thus far, only three alphaviruses with a host range restricted to insects have been found in mosquitoes from the Old World, namely Eilat virus (EILV), Taï Forest alphavirus (TALV) and Mwinilunga alphavirus (MWAV). In this stu...
Article
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RNA interference (RNAi) has strong antiviral activity in a range of animal phyla, but the extent to which RNAi controls virus infection in chordates, and specifically mammals remains incompletely understood. Here we analyze the antiviral activity of RNAi against a number of positive-sense RNA viruses using Argonaute-2 deficient human cells. In line...
Article
Full-text available
The RNA interference (RNAi) pathway is a potent antiviral defense mechanism in plants and invertebrates, in response to which viruses evolved suppressors of RNAi. In mammals, the first line of defense is mediated by the type I interferon system (IFN); however, the degree to which RNAi contributes to antiviral defense is still not completely underst...
Article
Full-text available
Small RNA mediated responses are essential for antiviral defence in mosquitoes, however, they appear to differ per virus-vector combination. To further investigate the diversity of small RNA responses against viruses in mosquitoes, we applied a small RNA deep sequencing approach on five mosquito cell lines: Culex tarsalis CT cells, Aedes albopictus...
Article
Full-text available
Stress responses are crucial processes that require activation of genetic programs that protect from the stressor. Stress responses are also energy consuming and can thus be deleterious to the organism. The mechanisms coordinating energy consumption during stress response in multicellular organisms are not well understood. Here, we show that loss o...
Article
Full-text available
Thrombocytopenia and platelet dysfunction are commonly observed in patients with dengue virus (DENV) infection and may contribute to complications such as bleeding and plasma leakage. The etiology of dengue-associated thrombocytopenia is multifactorial and includes increased platelet clearance. The binding of the coagulation protein von Willebrand...
Data
Platelet activation with impaired reactivity to TRAP in patients with acute dengue. Binding of fibrinogen to platelets and platelet P-selectin expression in unstimulated samples and after ex vivo stimulation with two concentrations of TRAP. (A, B) Data from Bandung cohort with longitudinal data from the different days of fever in dengue patients an...
Data
Flow cytometry gating strategy for determination of VWF binding to platelets. Platelets were gated based on forward and side scatter characteristics (A), followed by positivity for the platelet marker CD61-PC7 (B). The Median fluorescence intensity (MFI) of anti-VWF after stimulation (C) without agonist and (D) after ex vivo VWF-activation with ris...
Data
ADAMTS-13 activity in Bandung cohort. (A) Data from different days of fever in dengue patients and in healthy controls. Data are shown as geometric mean with 95% confidence interval. Differences between groups were analyzed using the Mann-Whitney U test. (B-D) The correlation between VWF binding to platelets without any agonist stimulation and plas...
Data
Differences in platelets and VWF parameters between dengue patients with and without bleeding, and patients with and without plasma leakage. Data shown are platelet numbers (A and B), VWF binding to platelets in the absence of an agonist (MFI) (C and D), Plasma VWF:Ag levels (E and F) and plasma active VWF levels (G and H). Differences between grou...
Data
Flow cytometry gating strategy for determination of sialic acid expression on platelets. Platelets were gated in P0 based on forward and side scatter characteristics (A) followed by positivity of the platelet marker CD61-PC7 in P1 (B). The median fluorescence intensity (MFI) of PE-labeled SNA lectin on platelets is determined from gate P1 (C, highe...
Data
Platelet desialylation is mediated by VWF binding to platelets. (A) Expression of Neuraminidase 1 (Neu-1) and binding of RCA lectin and VWF to platelets after incubation with two concentrations of DENV NS1 protein for 4 hrs at 37°C (n = 7 platelet donors). (B) Binding of VWF and RCA to platelets after incubating washed platelets with increasing con...
Data
Sialic acid expression and platelet reactivity in dengue patients with or without bleeding. Binding of the lectins (A) SNA and (B) MAL-II to platelet sialic acid residues were measured by flow cytometry in dengue patients with (n = 22) and without bleeding (n = 18). Platelet P-selectin expression and binding of fibrinogen to platelets in unstimulat...
Article
Full-text available
The fruit fly Drosophila melanogaster is a valuable model organism for the discovery and characterization of innate immune pathways, but host responses to virus infection remain incompletely understood. Here, we describe a novel player in host defense, Sgroppino (Sgp). Genetic depletion of Sgroppino causes hypersensitivity of adult flies to infecti...
Article
Commensal bacteria that colonize the midgut of Aedes aegypti mosquitoes can influence the transmission of arthropod-borne viruses. In this issue of Cell Host & Microbe, Wu et al. (2019) show that Serratia marcescens bacteria secrete enhancin proteins that cleave membrane-bound mucins, thereby facilitating dengue virus infection of midgut epithelial...
Article
Full-text available
PIWI-interacting RNAs (piRNAs) comprise a class of small RNAs best known for suppressing transposable elements in germline tissues. The vector mosquito Aedes aegypti encodes seven PIWI genes, four of which are somatically expressed. This somatic piRNA pathway generates piRNAs from viral RNA during infection with cytoplasmic RNA viruses through ping...
Article
Coevolution of multicellular organisms and their natural viruses may lead to an intricate relationship in which host survival requires effective immunity and virus survival depends on evasion of such responses. Insect antiviral immunity and reciprocal virus immunosuppression tactics have been well studied in Drosophila melanogaster , primarily duri...
Poster
Full-text available
Aedes albopictus is a public health threat for its worldwide spread and ability to transmit arboviruses. Understanding mechanisms of mosquito immunity can provide new tools to control arbovirus spread. Mosquito main antiviral mechanisms include two different RNAi pathways: the short interfering RNAs (siRNAs) and the PIWI-interacting RNAs (piRNAs) p...
Preprint
Full-text available
TUDOR-domain containing proteins facilitate PIWI interacting (pi)RNA biogenesis in Drosophila melanogaster and other model organisms. In Aedes aegypti mosquitoes, a somatically active piRNA pathway generates piRNAs from viral RNA during acute infection with cytoplasmic RNA viruses. Viral piRNA biogenesis requires ping-pong amplification by the PIWI...
Article
Full-text available
Dengue virus (DENV) is associated with an estimated 390 million infections per year, occurring across approximately 100 countries in tropical and sub-tropical regions. To date, there are no antiviral drugs or specific therapies to treat DENV infection. Posaconazole and itraconazole are potent antifungal drugs that inhibit ergosterol biosynthesis in...
Preprint
Full-text available
Interactions between the insect immune system and RNA viruses have been best studied in Drosophila, where RNA interference, NF-κB and JAK-STAT pathways underlie antiviral immunity. In response to these immune mechanisms, insect viruses have convergently evolved suppressors of RNA interference that act by diverse mechanisms to permit viral replicati...
Article
Full-text available
The power and ease of Drosophila genetics and the medical relevance of mosquito-transmitted viruses have made dipterans important model organisms in antiviral immunology. Studies of virus–host interactions at the molecular and population levels have illuminated determinants of resistance to virus infection. Here, we review the sources and nature of...
Chapter
Insects are the most abundant and diverse group of animals on earth, but our knowledge of their viruses is biased toward insect-borne viruses that cause disease in plants, animals, or humans. Recent metagenomic studies and systematic surveys of viruses in wild-caught insects have identified an unanticipated large repertoire of novel viruses and vir...