Biology subjects

Verheyen, E.

Publications and source records attributed to Verheyen, E..

12 recordsLinked to original sources

bioRxiv2026

The abnormal C-terminus in DVL1 impacts Robinow Syndrome phenotypes

Robinow Syndrome is a polygenic, rare skeletal disorder characterized by craniofacial and limb defects. The genes involved are in the Wingless-related Integration site-1 (WNT) pathway and DVL1 (Dishevelled 1) is the most commonly affected gene. In all pathogenic variants of DVL1, a frameshift replaces the C terminus with a novel peptide. We tested whether the variant DVL11519{Delta}T was sufficient to alter development in vivo and in vitro in two animal models. We compared phenotypes to wtDVL1 or DVL1 with a stop codon at position 1519. Misexpression of DVL11519{Delta}T in the developing face of chicken embryos with an avian retrovirus, leads to a widening of the frontonasal mass similar to the human facial phenotype and ultimately to inhibition of skeletogenesis that was also verified in primary cultures of frontonasal mass mesenchyme. In luciferase assays carried out in facial mesenchyme, the wtDVL1 activated canonical and JNK PCP WNT signalling however the DVL11519* and the DVL11519{Delta}T variant removed some but not all of the signaling activity. We also determined that there is mislocalization of the protein expressed from DVL11519{Delta}T in the nucleus while the other two constructs were mainly found in the cytoplasm. In complementary Drosophila experiments using a variety of readouts, only the DVL11519{Delta}T variant impacted morphogenesis and signaling. This is the first study to clarify the pathogenesis of Robinow syndrome is due to the novel C-terminus of DVL1 which exerts dominant interference on morphogenesis, skeletogenesis and WNT signaling.

developmental biology↗

bioRxiv2025

A Novel Drosophila Model of Cancer Cachexia Reveals Conserved Jak/Stat Dependent Glucagon-like Akh Activation as a Driver of Metabolic Reprogramming and Systemic Wasting

Cancer-associated cachexia is a systemic wasting syndrome with no effective therapies, and results in millions of deaths annually. Here, we establish a novel Drosophila model of cancer cachexia using overexpression of Hipk and constitutively active Sik3 in larval epithelial tissue. Tumor-bearing larvae has significant muscle and fat body wasting, together with elevated carbohydrates and lipolysis. Mechanistically, tumors secrete Unpaired ligands that activate Jak/Stat signaling in corpora cardiaca (cc) cells, inducing the expression and protein levels of glucagon-like hormone Adipokinetic hormone (Akh). Elevated Akh, together with the lipase Brummer (Bmm), drives the aforementioned systemic metabolic reprogramming and tissue catabolism. In conclusion, this study identifies a conserved tumor-host Upd-JAK/STAT-Akh signaling axis that contributes to organ wasting.

cancer biology↗

bioRxiv2025

Uncovering functional insights into human pathogenic variants in CDK19 using Drosophila models

Heterozygous missense variants in CDK19 have been found in patients diagnosed with Developmental and epileptic encephalopathy-87 (DEE87) who present with global developmental delay, intellectual disability and other muscular and neurological deficiencies. Two missense variants in CDK19, Y32H and T196A, were first proposed to be dominant negative in nature based on experiments in a Drosophila model. Subsequently, another group proposed that Y32H is a gain of function based on elevated kinase activity. We present a detailed evaluation of the activity and functionality of these dominant variants in several contexts in fly models of DEE-87 in which endogenous cdk8, the fly ortholog of human CDK8 and CDK19, is knocked down while we overexpressed the human genes. Depletion of Drosophila cdk8 causes thicker muscle myofibrils, fused mitochondria, and climbing defects. The expression of human CDK19WT in a fly cdk8-RNAi background rescues these defects, highlighting functional conservation. To investigate functional differences between the variants, we compared effects of variants to expression of wildtype CDK19. Ubiquitous expression of Y32H can rescue the cdk8 knockdown phenotype through a gain of function compensatory effect, while T196A is unable to do so through a possible reduction in kinase activity. We found that supplementation of the antioxidant drug, N-acetylcysteine amide (NACA), rescues phenotypes of only the T196A adult flies, illustrating a divergence in variant functionality. Our studies in flies allowed us to assay these variants in numerous contexts to gain further insight into their mechanism and obtain translational knowledge to apply back to human health.

genetics↗

bioRxiv2025

Reassessing the diversity and distribution of African rope squirrels (Funisciurus Trouessart, 1880)

The diversity, taxonomy, distribution and ecology of sub-Saharan tree squirrels remain under-researched. This study aims to elucidate the diversity and distribution of rope squirrels, genus Funisciurus Trouessart 1880, in the Congo Basin. We assembled the most comprehensive genetic and morphometric data set to date, on a significant portion of the geographical and taxonomic range of these squirrels (470 specimens from seven provinces of the Democratic Republic of Congo). We identified six main taxa: a previously undescribed Funisciurus species (here, Fx), three allopatric taxa of Funisciurus anerythrus (Fc, FaRB and FaLB), and two sympatric genetically distinct taxa (FbLB1, FbLB2), potentially belonging to a Funisciurus bayonii species complex. We then mapped their distribution, showing that the Congo and Kasai Rivers represent significant biogeographical barriers limiting the distribution of Funisciurus species. In addition to providing a baseline for research on the impact of climate change and habitat degradation on the abundance and distribution of rope squirrels, our findings support research on the role of rope squirrel species in the transmission of pathogens of public health importance. Teaser textWe studied the diversity and distribution of rope squirrels, genus Funisciurus Trouessart 1880, in the Congo Basin. By gathering the most comprehensive genetic and morphometric data to date on a significant part of the geographical and taxonomic range of these squirrels (specimens from seven provinces of the Democratic Republic of Congo), we identified six main taxa: one previously undescribed species, three allopatric taxa, and two genetically distinct sympatric taxa. We then mapped their distribution, showing that the Congo and Kasai rivers represent significant biogeographical barriers limiting the distribution of Funisciurus species. These results support research into the role of rope squirrel species in the transmission of pathogens of public health importance. Image for the online table of contents: African rope squirrel Photo credit: Bushnell photo trap set by Pascal Baelo

zoology↗

bioRxiv2025

High genetic diversity of mpox virus (MPXV) in three different rodent species in the Democratic Republic of the Congo (DRC)

Altough zoonotic spillover events continue to drive human mpox outbreaks in the Democratic Republic of the Congo (DRC), the wildlife reservoir of mpox virus (MPXV) remains unkown. To address this gap, we screened samples from 2,701 wild mammals, mainly rodents (59.7%), bats (26.4%) and shrews (12.1%). Only six (0.2%) animals were Orthopoxvirus (OPV) PCR positive. Near full-length MPXV sequences were obtained from two squirrels (Funisciurus anerythrus and Paraxerus sp.) and one soft furred mouse (Praomys jacksoni). A novel Taterapox virus was identified in a shrew (Crocidura cf. denti). All newly identified MPXV strains belong to clade Ia, but they cluster into different groups or subgroups, despite being collected from geographically close locations, and all are closely related to human MPXV strainsfrom the same regions. Our study provides for the first time clear evidence that MPXV diversity is not restricted to a single rodent host species nor confined to a geographic area. Importantly, MPXV positive Paraxerus and Praomys specimens were sampled close to Kisangani, a city with more than one million inhabitants, highlighting that spillover events can als ooccur in or near major cities, with more favorable conditions for interhuman transmissions and potential emergence of new lineages.

microbiology↗

bioRxiv2024

A wide diversity of viruses detected in African mammals involved in the wild meat supply chain

The processes involved in acquiring, trading, preparing, and consuming wild meat pose significant risks for the emergence of zoonotic infectious diseases. Several major viral outbreaks have been directly linked to the wild meat supply chain, yet our knowledge of the virome in many mammals involved in this chain remains limited and disproportionately focused on certain mammalian taxa and pathogens. This report presents the findings of a metagenomic viral screening of 99 specimens belonging to 27 wild African mammal species and one domesticated species, all traded for their meat. The study focuses on tissue and swab samples collected from various regions in the Democratic Republic of the Congo and in Brussels, Belgium. A total of fifteen virus strains were detected, belonging to the families Arteriviridae, Retroviridae and Sedoreoviridae (primates), Picobirnaviridae (primates and rodents), Picornaviridae (rodents), Hepadnaviridae (hyrax), Orthoherpesviridae (artiodactylid and carnivore) and Spinareoviridae (carnivore). Several strains were detected in mammalian hosts for the first time, expanding their host range and genetic diversity. Of note is the presence of viruses genetically related to recognised zoonotic pathogens, i.e., human picobirnavirus (Orthopicobirnavirus hominis) (primates and rodents), simian foamy viruses (Simiispumavirus) (primates), and rotavirus A (Rotavirus alphagastroenteritidis) (primates). The presence of these viruses in primates is concerning as non-human primates are phylogenetically closely related to humans, which can facilitate interspecies viral transmission. These findings underscore the high diversity of mammalian viruses and the potential risk of human infection through cross-species transmission during the close interactions with wildlife in the wild meat supply chain.

genomics↗

bioRxiv2024

Assessing Ebola Virus Circulation in the Tshuapa Province (Democratic Republic of the Congo): A One Health Investigation of Wildlife and Human Interactions

The wildlife reservoir and spillover mechanisms of the Ebola virus remain elusive despite extensive research efforts in endemic areas. This study employed a One Health approach to examine the virus circulation in wildlife and the associated human exposure risks in the Tshuapa province of the Democratic Republic of the Congo. In 2021, we collected 1015 samples from 888 animals, predominantly small mammals, and 380 inhabitants of Inkanamongo village, the site of an Ebola virus disease outbreak in 2014. These samples were screened for evidence of current (RNA) or past (IgG antibodies) Ebola virus infections. We also conducted interviews with 167 individuals in the surrounding districts to assess their interactions with wildlife. While no Ebola virus RNA was detected in the wildlife samples, anti-orthoebolavirus IgG antibodies were found in 13 bats and 38 rodents. Among the human participants, 120 individuals had IgG antibodies against at least one orthoebolavirus antigen, with 12 showing seropositivity for two antigens of the same orthoebolavirus, despite not having a prior Ebola disease diagnosis. Furthermore, over 50% of respondents reported frequent visits to the forest to hunt a variety of wild animals, particularly ungulates and rodents, which could account for occasional viral spillovers. The absence of active Ebola virus circulation in wildlife may reflect seasonal patterns in reservoir ecology, like those observed in bats. Similarly, seasonal human activities, like hunting and foraging, may result in periodic exposure risks. These findings highlight the importance of continuous, multidisciplinary surveillance to monitor changes in seasonal spillover risks.

molecular biology↗

bioRxiv2024

Antibodies against medically relevant arthropod-borne viruses in the ubiquitous African rodent Mastomy natalensis

Over the past decades, the number of arthropod-borne virus (arbovirus) outbreaks has increased worldwide. Knowledge regarding the sylvatic cycle (i.e., non-human hosts/environment) of arboviruses is limited, particularly in Africa, and the main hosts for virus maintenance are unknown. Previous studies have shown the presence of antibodies against certain arboviruses (i.e., chikungunya-, dengue- and zika virus) in African non-human primates and bats. We hypothesize that small mammals, specifically rodents, may function as amplifying hosts in anthropogenic environments. The detection of RNA of most arboviruses is complicated by the viruss short viremic period within their hosts. An alternative to determine arbovirus hosts is by detecting antibodies, which can persist several months. We developed a high-throughput multiplex immunoassay to detect antibodies against 15 medically relevant arboviruses. We used this assay to assess almost 1,300 blood samples of the multimammate mouse, Mastomys natalensis from Tanzania. In 24% of the samples, we detected antibodies against at least one of the tested arboviruses, with high seroprevalences of antibodies reacting against dengue virus serotype one (7.6%) and two (8.4%) and chikungunya virus (6%). Seroprevalence was higher in females and increased with age, which could be explained by inherent immunity and behavioral differences between sexes and the increased chance of exposure to an arbovirus with age. We evaluated whether antibodies against multiple arboviruses co-occur more often than randomly and found that this may be true for some members of the Flaviviridae and Togaviridae. In conclusion, the development of an assay against a wide diversity of medically relevant arboviruses enabled the analysis of a large sample collection of one of the most abundant African small mammals. Our findings suggest a role in the transmission of multiple arboviruses by this ubiquitous rodent and provide a solid foundation for future molecular screening to elucidate the role in the arbovirus transmission cycle. Author summaryOne of the main causes of zoonotic related human morbidity and mortality is the transmission of arthropod-borne viruses such as dengue virus, Yellow Fever virus, and chikungunya virus. These viruses cannot only infect humans but also livestock, pets, and wildlife, though our understanding of their non-human hosts remains limited. Rodents are thought to be an interesting host for these viruses because they can be abundant, often live near humans and some are already known to be viral hosts. However, research has focused on non-human primates, neglecting other potential hosts. To address this gap, we have developed a high-throughput antibody test to screen rodent blood against 15 different arboviruses. Our findings reveal that a proportion of Mastomys natalensis, a common African rodent species, carry antibodies that (cross-)react against these viruses. We hypothesize that immunologically naive juveniles may drive transmission, particularly during population outbreaks. These outbreaks coincide with environmental conditions that are favorable for mosquitoes, the vectors of these viruses. Thus, increasing the risk of spillover to humans, livestock, and wildlife. Understanding the role of rodents in arbovirus transmission dynamics is crucial for mitigating zoonotic disease risks.

immunology↗

bioRxiv2023

The evolutionary history of hepaciviruses

In the search for natural reservoirs of hepatitis C virus (HCV), a broad diversity of non-human viruses within the Hepacivirus genus has been uncovered. However, the evolutionary dynamics that shaped the diversity and timescale of hepaciviruses evolution remain elusive. To gain further insights into the origins and evolution of this genus, we screened a large dataset of wild mammal samples (n = 1,672) from Africa and Asia, and generated 34 full-length hepacivirus genomes. Phylogenetic analysis of these data together with publicly available genomes emphasizes the importance of rodents as hepacivirus hosts and we identify 13 rodent species and 3 rodent genera (in Cricetidae and Muridae families) as novel hosts of hepaciviruses. Through co-phylogenetic analyses, we demonstrate that hepacivirus diversity has been affected by cross-species transmission events against the backdrop of detectable signal of virus-host co-divergence in the deep evolutionary history. Using a Bayesian phylogenetic multidimensional scaling approach, we explore the extent to which host relatedness and geographic distances have structured present-day hepacivirus diversity. Our results provide evidence for a substantial structuring of mammalian hepacivirus diversity by host as well as geography, with a somewhat more irregular diffusion process in geographic space. Finally, using a mechanistic model that accounts for substitution saturation, we provide the first formal estimates of the timescale of hepacivirus evolution and estimate the origin of the genus to be about 22 million years ago. Our results offer a comprehensive overview of the micro- and macroevolutionary processes that have shaped hepacivirus diversity and enhance our understanding of the long-term evolution of the Hepacivirus genus. SignificanceSince the discovery of Hepatitis C virus, the search for animal virus homologues has gained significant traction, opening up new opportunities to study their origins and long-term evolutionary dynamics. Capitalizing on a large-scale screening of wild mammals, and genomic sequencing, we expand the novel rodent host range of hepaciviruses and document further virus diversity. We infer a significant influence of frequent cross-species transmission as well as some signal for virus-host co-divergence, and find comparative host and geographic structure. We also provide the first formal estimates of the timescale of hepaciviruses indicating an origin of about 22 million years ago. Our study offers new insights in hepacivirus evolutionary dynamics with broadly applicable methods that can support future research in virus evolution.

microbiology↗

bioRxiv2023

SARS-CoV-2 surveillance between 2020 and 2021 of all mammalian species in two Flemish zoos (Antwerp Zoo and Planckendael Zoo)

The COVID-19 pandemic has led to millions of human infections and deaths worldwide. Several other mammal species are also susceptible to SARS-CoV-2, and multiple instances of transmission from humans to pets, farmed mink, wildlife and zoo animals have been recorded. We conducted a systematic surveillance of SARS-CoV-2 in all mammal species in two zoos in Belgium between September and December 2020 and July 2021 in four sessions, and a targeted surveillance of selected mammal enclosures following SARS-CoV-2 infection in hippos in December 2021. A total of 1523 faecal samples were tested for SARS-CoV-2 via real-time PCR. None of the samples tested positive for SARS-CoV-2. Additional surrogate virus neutralization tests conducted on 50 routinely collected serum samples during the same period were all negative. This study is a first to our knowledge to conduct active SARS-CoV-2 surveillance for several months in all mammal species of a zoo. We conclude that at the time of our investigation, none of the screened animals were excreting SARS-CoV-2.

molecular biology↗

bioRxiv2021

The initial response of females towards congeneric males matches the propensity to hybridize in Ophthalmotilapia.

AO_SCPLOWBSTRACTC_SCPLOWCichlid radiations often harbour closely related species with overlapping niches and distribution ranges. Such species sometimes hybridise in nature, which raises the question how can they coexist. This also holds for the Tanganyika mouthbrooders Ophthalmotilapia ventralis and O. nasuta. Earlier studies found indications of asymmetrical hybridisation with females of O. ventralis accepting males of O. nasuta, but not the other way around. We hypothesised that this was due to differences in the capacity for species recognition. Given the higher propensity of O. ventralis females towards hybridisation, we expect a reduced ability for species recognition in O. ventralis females, compared to O. nasuta females. We staged two experiments, one focusing on 22 female O. nasuta and one on 21 female O. ventralis. These fish were placed in one half of a tank and briefly exposed to a conspecific or a heterospecific male, a conspecific female, or nothing (control). Female response was evaluated by scoring six tracking parameters and by noting the occurrence of ten discrete behaviours before and during the encounter. Females always responded to the presence of another fish by approaching it. Remarkably, for both O. nasuta and O. ventralis, we did not find a different response between encounters with conspecific males and females. However, in agreement with our hypothesis, O. nasuta females behaved differently towards conspecific or heterospecific males, whereas O. ventralis females did not. When presented with a heterospecific male, O. nasuta females performed a lower number of ram behaviours. Additionally, they never displayed the flee behaviour, a component of the species mating repertoire that was seen in all but one of the presentations with a conspecific male. Our findings show that differences in species recognition at first encounter predict to a large degree the outcome of the mating process, even in the absence of mating behaviour.

animal behavior and cognition↗

bioRxiv2020

Unravelling the evolutionary relationships of hepaciviruses within and across rodent hosts

Hepatitis C virus (HCV; genus Hepacivirus) represents a major public health problem, infecting about 3 % of the human population ({+/-} 185,000,000 people). Because no plausible animal reservoir carrying closely related hepaciviruses has been identified, the zoonotic origins of HCV still remain elusive. Motivated by recent findings of divergent hepaciviruses in rodents and a plausible African origin of HCV genotypes, we have screened a comprehensive collection of small mammals samples from seven sub-Saharan African countries. Out of 4,303 samples screened, 80 were found positive for the presence of hepaciviruses in 29 different host species. We here report 56 novel genomes that considerably increase the diversity of three divergent rodent hepacivirus lineages, which previously were almost exclusively represented by New World and European hepaciviruses. Further-more, we provide undisputable evidence for hepacivirus co-infections in rodents, which remarkably, we exclusively but repeatedly found in four sampled species of brush-furred mice. We also point at hepacivirus co-infections indirectly in different animal hosts by demonstrating evidence for recombination within specific host lineages. Our study considerably expands the available hepacivirus genomic data and elucidates the relatively deep evolutionary history that these pathogens have in rodents compared to other mammalian hosts. Overall, our results emphasize the importance of rodents as a potential hepacivirus reservoir and as models for investigating HCV infection dynamics.

evolutionary biology↗