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Marien, J.

Publications and source records attributed to Marien, J..

18 recordsLinked to original sources

Deep-learning predictions of biomolecular structures : persistent limitations and new horizons extended by explicit ion addition

The advent of deep learning-driven tools such as AlphaFold has revolutionized the prediction of biomolecular structures, offering unprecedented accuracy and accessibility for proteins, RNA, and their complexes. While these tools have demonstrated remarkable success in benchmarking competitions and enabled experimentalists to generate models with ease, their widespread use has also highlighted persistent challenges. These include difficulties in assessing model confidence, limitations in predicting transmembrane domains, nucleic acids, conformational diversity, and interactions with ions or ligands, as well as the tendency to misfold intrinsically disordered regions (IDRs). In this perspective, we critically evaluate the strengths and limitations of current AI-based structure prediction tools through illustrative examples with a particular emphasis on the impact of explicit ion modelling. We notably report how the explicit addition of a few potassium cations to the prediction of IDRs or G-quadruplexes can trigger massive conformational switches compared to "dry" predictions. On this basis, we suggest modelling sequences both "dry" and in the presence of explicit potassium cations as a simple, practical way to sample alternative conformations and to expose disordered regions that current predictors tend to over-fold. We discuss the importance of reporting confidence metrics in publications to avoid overinterpretation. Furthermore, we address the unique challenges of RNA structure prediction, where data scarcity and structural complexity limit the performance of both classical and deep learning methods. Our analysis underscores the need for continued methodological advancements, integration of complementary computational tools, and expansion of high-quality experimental datasets. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/740587v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@e950e9org.highwire.dtl.DTLVardef@1bf22b3org.highwire.dtl.DTLVardef@17f5229org.highwire.dtl.DTLVardef@1eb2e9f_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

Simulations of an extended Tau/tubulins interface reveal a complex disorder-disorder interplay mediated by the C-terminal tails

Building on a complex between a tubulin protofilament (PF) and a fragment of the Tau protein containing residues 169 to 367, we investigate the dynamics of the disordered elements of the system, namely the tubulin C-terminal tails (CTTs) and the Tau protein, using classical all-atom molecular dynamics simulations. Our results show that CTTs adopt a hook-like dynamic pattern on the bare PF while remaining highly mobile. The binding of Tau on the PF surface alters the dynamics of the I-CTTs in a sequence-dependent manner. While the repeat domains of Tau are mostly maintained on the PF by weak and strong binding patches with the tubulin cores, the Proline-Rich Region (PRR) relies on the wrapping phenomenon of I-CTTs to fuzzily stabilize its interaction with the PF. Our study thus provides a deep dive into the dynamic interplay between the Tau protein and the CTTs of microtubules, the latter being characterized extensively using a variety of disorder-adapted metrics. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/721901v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@b3f985org.highwire.dtl.DTLVardef@1c2bf70org.highwire.dtl.DTLVardef@a66b95org.highwire.dtl.DTLVardef@1e138e0_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Longitudinal Profiling of CD4⁺ T Cell Responses Following de novo Yellow Fever Vaccination

The yellow fever 17D vaccine is one of the most successful live-attenuated viral vaccines, yet the cellular mechanisms underlying its long-term protection remain not fully understood. This study provides a longitudinal analysis of the human CD4+ T cell and IgG response following de novo yellow fever vaccination by focusing. Peripheral blood mononuclear cells (PBMCs) from 49 vaccinated individuals were stimulated with yellow fever (YF) and control peptide pools across four timepoints: pre-vaccination/baseline (D1), day 22 (D22), day 43 (D43), and one year (D365) post-vaccination. Activation-induced marker (AIM) assays confirmed robust activation of CD4+ T cells following yellow fever peptide stimulation, peaking at day 22 post-vaccination and subsequently declining. T-cell receptor (TCR{beta}) sequencing of AIM-sorted CD4+ T cells showed a transient increase in clonal diversity at D22, consistent with broad epitope targeting and early polyclonal expansion. This was followed by repertoire contraction, which could indicate the persistence of a limited set of dominant clonotypes responsible for immune memory formation. TCR repertoires remained largely private over time, indicating a mostly individualized immune response. Next, serological analyses revealed a robust and highly yellow fever virus (YFV)-specific IgG response. Antibody levels peaked within the D22-D43 window and remained elevated at one year post-vaccination. Cross-reactivity toward other flaviviruses was limited, suggesting an antigen-specific humoral response. Together, these findings characterize the longitudinal dynamics of the CD4+ T cell and IgG response following de novo yellow fever vaccination and provide insights into the mechanisms contributing to durable antiviral immunity.

immunology↗

Additive effects of environmental and demographic variation shape the repeatability of evolution across replicated experiments

The repeatability of evolution is fundamentally important for understanding the origin and diversification of life as well as for developing evolutionary forecasting tools. Repeatability is limited by stochasticity, here defined as changes that are independent of genotypic fitness effects. Over short timescales, the two main sources of stochasticity of evolutionary change are environmental stochasticity and demographic (life-history) stochasticity. Quantifying the relative importance of these two sources of stochasticity in driving fitness outcomes is crucially important for predicting evolutionary responses. To gain insights in the effects of stochasticity, five institutes replicated an evolutionary experiment exposing Caenorhabditis elegans to novel rearing conditions. Replication across the institutes led to variation in selective environments, e.g. through divergent microbiomes among institutes. Replication within institutes was done across demographic treatments that influence the potential for population-size dependent fluctuations in allele frequencies (drift) and genetic hitchhiking (draft). We found high among-institute variation in fitness outcomes, which was partially explained by variation in microbiota. Whereas lab-specific effects explained most of the variance in mean fitness, the repeatability of fitness outcomes depended more on demographic heterogeneity. Specifically, population bottlenecks resulted in high among-replicate variation in fitness. When combined, environmental and demographic stochasticity additively reduced repeatability, underlining their additive importance in developing evolutionary forecasting tools. These results further highlight the importance of statistically integrating heterogeneity in experimental evolution to identify factors constraining outcome repeatability and study replicability.

evolutionary biology↗

Sticky salts: overbinding of monovalent cations to phosphorylations in all-atom forcefields

Phosphorylation is a major post-translational modification, which is involved in the regulation of the dynamics and function of Intrinsically Disordered Proteins (IDPs). We recently characterized a phenomenon, which we termed n-Phosphate collaborations (nP-collabs), where bulk cations form stable bridges between several phosphoresidues in all-atom molecular dynamic simulations. nP-collabs were found to be sensitive to the combination of forcefields and cation types. Here, we attempt to assess the physical relevance of these nP-collabs by evaluating the strength of the cation/phosphate interaction through osmotic coefficient ({phi}) calculations on the model [Formula] and [Formula] salts, using different classical forcefields for phosphorylations. All force-fields were found to overestimate the strength of the interaction to various degrees. We thus designed new parameters for CHARMM36m and AmberFF99SB-ILDN using the Electronic Continuum Correction (ECC) approach, which provide remarkable agreement for{phi} values for both cation types and over a range of concentrations. We provide a preliminary test of these ECC parameters for phosphorylations by simulating the sevenfold-phosphorylated rhodopsin peptide 7PP and comparing secondary chemical shifts to experimental data. Conformational ensembles resulting from the ECC-derived phosphorylated forcefields display both qualitative and quantitative improvements with regard to full-charge forcefields. We thus conclude that long-lasting nP-collabs are artifacts for classical forcefields born from the lack of explicit polarization, and propose a possible computational strategy for the extensive parameterization of phosphorylations. The presence of long-lived nP-collabs in simulations produced using classical forcefields is therefore a serious concern for the accurate modelling of multiphosphorylated peptides and IDPs, which are at the center of research questions regarding neurodegenerative diseases such as Alzheimers or Parkinsons.

biochemistry↗

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↗

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↗

Across (conformational) space and (relaxation) time: using coarse-grainsimulations to probe the intra- and interdomain dynamics of the Tau protein

The biological importance of intrinsically disordered proteins (IDP) has been established for over two decades, yet these systems remain difficult to characterize, as they are better described by conformational ensembles instead of a single reference structure for their folded counterparts. Tau is a prominent member of the IDP family which sees its cellular function regulated by multiple phosphorylations sites, and whose hyperphosphorylation is involved in neurodegenerative diseases such as Alzheimers. We use coarse-grain MD simulations with the CALVADOS model to investigate the conformational landscape of tau without and with phosphorylations. Characterizing the local compactness of IDPs allows us to highlight how disorder comes in various flavors, as we can define different domains along the tau sequence. We define the IDPs Statistical Tertiary Organization (STO) as the average spatial arrangements of domains, which constitutes an extension of the tertiary structure of folded proteins. We also use IDP specific metrics to characterize the local curvature and flexibility of tau. Comparing the local flexibilities with T2 relaxation times from NMR experiments, we show how this metric is related to the protein dynamics. A curvature and flexibility pattern in the repeat domains can also be connected to tau binding properties, without having to explicitly model the proteins interaction partner. Finally, we rediscuss the original paperclip model that describes the spatial organization of tau, and how phosphorylations impact it. The resulting changes in the protein intra- and interdomain interaction pattern allow us to propose experimental setups to test our hypothesis. TOC graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/665865v3_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@7b7fc5org.highwire.dtl.DTLVardef@182a9org.highwire.dtl.DTLVardef@129515borg.highwire.dtl.DTLVardef@19c6d8f_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Menger_Curvature : a MDAKit implementation to decipher the dynamics, curvatures and flexibilities of polymeric backbones at the residue level

Characterizing the dynamics of the backbone of flexible polymers such as Intrinsically Disordered Regions and Proteins (IDRs and IDPs) has proven to be a significant challenge in molecular dynamics (MD) simulations due to their high conformational variability. The widely-used mobility metric Root-Mean-Squared Fluctuations (RMSF) is powerless to provide information for highly flexible systems, as defining a relevant reference structure is often not possible. We previously introduced a new flexibility metric to remedy this gap : the Local Flexibilities (LFs), derived (alongside the Local Curvatures (LCs)) from the Proteic Menger Curvatures (PMCs). Here we present a numba accelerated implementation for any polymer of the calculation of Menger Curvatures as a MDAKit from the widely-used MDAnalysis package. We perform a benchmark with the RMSF and another flexibility metric derived from Proteic Blocks (PBs), the Equivalent Number of PBs (Neq), and show that the PMCs are an order of magnitude faster to compute on a modern CPU chip. We applied all 3 flexibility metrics to a {beta}III-tubulin monomer as an example, as tubulins are known to possess the entire range of proteic elements, from -helix and {beta}-sheets to a flexible loop and a disordered C-terminal tail (CTT). RMSF, LFs and Neq all succeed in identifying the flexible loops and the CTT, although the RMSF requires a system-specific alignment to do so. Finally, we expose different applications of PMCs, LCs and LFs ranging from mechanism characterization to NMR T2 predictions. We believe that Menger curvatures will prove to be a valuable metric to study protein dynamics and polymers in general. The MDAKit package Menger_Curvature is readily available at https://github.com/EtienneReboul/menger_curvature

bioinformatics↗

Hydrodynamic Radius Determination of Tau and AT8 Phosphorylated Tau Mutants: A Combined Simulation and Experimental Study

Hyperphosphorylated Tau is a hallmark of Alzheimers disease leading to functional loss and fibrillar inclusions. We aim to understand how AT8 phosphorylation affects the Taus conformation and dynamics during early pathological transformation. We engineered an alanine Tau mutant to target specific phosphorylation sites restricted to the AT8 epitope, generating two distinct phosphorylation states. Using a combination of biophysical methods, and pCALVADOS forcefield, we found that AT8 phosphorylation do not alter the hydrodynamic radius or overall dynamics of Tau. Simulations revealed that local stiffening and extension at the AT8 epitope scale with phosphorylation extent. Interestingly, phosphorylation induces distant contact losses toward the N-terminus. This study advances our understanding of the structure-function-dynamics relationship of Tau in neurodegeneration.

biophysics↗

Impact of multiple phosphorylations on the tau-R2/tubulin interface

The phosphorylation of the microtubule-associated tau protein plays a key role in the regulation of its physiological function. In particular, tau hyperphosphorylation affects its binding on the tubulin surface, destabilizing the tau-microtubule interface and leading to the accumulation of fibrillar aggregates in the brain. In this work, we performed classical Molecular Dynamics simulations for the tau-R2/tubulin assembly with various phosphorylations states of serines 285, 289 and 293. We analyze the resulting trajectories to obtain a detailed view of the protein interface in the complex, and the impact of tau phosphorylations on the stability of this assembly, and on the tubulin disordered C-Terminal tails (CTTs) mobility. We show how the tubulin CTTs help maintaining the tau-R2 fragment on the tubulin surface despite the destabilizing effect induced by phosphorylations. Conversely, tau phosphorylation affects the CTTs flexibility and their potential activity as MAP recruiting hooks. Furthermore, counterion mediated bridges between the phosphate groups and tubulin glutamates also contribute to the binding of tau-R2 on the MT. Overall, the complex dynamics of this fuzzy phosphorylated assembly sheds a new light on the importance of the cytoplasmic environment in neurons in the context of Alzheimers disease.

biochemistry↗

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↗

nP-collabs: Investigating counterion mediated bridges in the multiply phosphorylated tau-R2 repeat

Tau is an instrinsically disordered (IDP), microtubule-associated protein (MAP) that plays a key part in microtubule assembly and organization. The function of tau can be regulated via multiple phosphorylation sites. These post-translational modifications are known to decrease the binding affinity of tau for microtubules, and abnormal tau phosphorylation patterns are involved in Alzheimers disease. Using all-atom molecular dynamics (MD) simulations, we compared the conformational landscapes explored by the tau R2 repeat domain (which comprises a strong tubulin binding site) in its native state and with multiple phosphorylations on the S285, S289 and S293 residues, with four different standard force field (FF)/water model combinations. We find that the different parameters used for the phosphate groups (which can be more or less flexible) in these FFs, and the specific interactions between bulk cations and water lead to the formation of a specific type of counterion bridge, termed nP-collab (for nPhosphate collaboration, with n being an integer), where counterions form stable structures binding with two or three phosphate groups simultaneously. The resulting effect of nP-collabs on the tau-R2 conformational space differs when using sodium or potassium cations, and is likely to impact the peptide overall dynamics, and how this MAP interacts with tubulins. We also investigated the effect of phosphoresidues spacing and ionic concentration by modeling polyalanine peptides containing two phosphoserines located one to six residues apart. Three new metrics specifically tailored for IDPs (Proteic Menger Curvature, Local Curvature and Local Flexibility) were introduced, which allow us to fully characterize the impact of nP-collabs on the dynamics of disordered peptides at the residue level. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/590060v2_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1b1b599org.highwire.dtl.DTLVardef@99047org.highwire.dtl.DTLVardef@1df34b9org.highwire.dtl.DTLVardef@fe60b2_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

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↗

It takes two to tango: Investigating the fuzzy interaction between tau and tubulin C-terminal tails

The microtubule-associated protein (MAP) tau plays a key role in the regulation of microtubule assembly and spatial organisation. Tau hyperphosphorylation affects its binding on the tubulin surface and has been shown to be involved in several pathologies such as Alzheimer disease. As the tau binding site on the microtubule lays close to the disordered and highly flexible tubulin C-terminal tails (CTTs), these are likely to impact the tau-tubulin interaction. Since the disordered tubulin CTTs are missing from the available experimental structures, we used homology modeling to build two complete models of tubulin heterotrimers with different isotypes for the {beta}-tubulin subunit ({beta}I/I/ {beta}I and {beta}III/I/{beta}III). We then performed long timescale classical Molecular Dynamics simulations for the tau-R2/tubulin assembly (in systems with and without CTTs) and analyzed the resulting trajectories to obtain a detailed view of the protein interface in the complex and the impact of the CTTs on the stability of this assembly. Additional analyses of the CTTs mobility in the presence, or in the absence, of tau also highlight how tau might modulate the CTTs activity as hooks that are involved in the recruitment of several MAPs. In particular, we observe a wrapping mechanism, where the {beta}-tubulin CTTs form a loop over tau-R2, thus stabilizing its interaction with the tubulin surface and simultaneously reducing the CTTs availability for interactions with other MAPs.

biochemistry↗

First observation of Aedes albopictus in the Tshuapa province (Boende) of the Democratic Republic of the Congo

In May-June 2021, we detected Aedes albopictus adults near the central hospital in Boende, the capital city of the Tshuapa province of the Democratic Republic of the Congo (DRC). We identified the mosquitoes using morphological and molecular techniques (COI barcoding). This is the first report of this species in the DRC outside of Kinshasa and Kongo Central. Given the central location of Boende in the Congo Basin, our finding suggests that the vector might also have spread to other cities which are located upstream of the Congo River and its major tributaries. Because Aedes albopictus is an important vector for human arbovirus transmission, we highlight the need to investigate its distribution range and to update disease risk maps in Central Africa.

evolutionary biology↗

SARS-CoV-2 surveillance in Norway rats (Rattus norvergicus) from Antwerp sewer system, Belgium

BackgroundSARS-CoV-2 human-to-animal transmission can lead to the establishment of novel reservoirs and the evolution of new variants with the potential to start new outbreaks in humans. AimWe tested Norway rats inhabiting the sewer system of Antwerp, Belgium, for the presence of SARS-CoV-2 following a local COVID-19 epidemic peak. In addition, we discuss the use and interpretation of SARS-CoV-2 serological tests on non-human samples. MethodsBetween November and December 2020, Norway rat oral swabs, feces and tissues from the sewer system of Antwerp were collected to be tested by RT-qPCR for the presence of SARS-CoV-2. Serum samples were screened for the presence of anti-SARS-CoV-2 IgG antibodies using a Luminex microsphere immunoassay (MIA). Samples considered positive were then checked for neutralizing antibodies using a conventional viral neutralization test (cVNT). ResultsThe serum of 35 rats was tested by MIA showing 3 potentially positive sera that were later shown to be negative by cVNT. All tissue samples of 39 rats analyzed tested negative for SARS-CoV-2 RNA. ConclusionThis is the first study that evaluates SARS-CoV-2 infection in urban rats. We can conclude that the sample of 39 rats had never been infected with SARS-CoV-2. We show that diagnostic serology tests can give misleading results when applied on non-human samples. SARS-CoV-2 monitoring activities should continue due to the emergence of new variants prone to infect Muridae rodents.

ecology↗

Comparing arenavirus infection patterns in experimentally and naturally infected rodent hosts

Infectious diseases of wildlife are typically studied using data on antibody and pathogen presence/level. In order to interpret these data, it is necessary to know the course of antibodies and pathogen presence/levels after infection. Such data are typically collected using experimental infection studies in which host individuals are inoculated in the laboratory and sampled over an extended period, but because laboratory conditions are controlled and much less variable than natural conditions, the immune response and pathogen dynamics may differ. Here, we compared Morogoro arenavirus infection patterns between naturally and experimentally infected multimammate mice (Mastomys natalensis). Longitudinal samples were collected during three months of bi-weekly trapping in Morogoro, Tanzania, and antibody titer and viral RNA presence were determined to assess whether the natural temporal patterns are similar to those previously observed in the laboratory. A good match with laboratory data was found for 52% of naturally infected individuals, while most of the mismatches can be explained by the presence of chronically infected individuals (35%), maternal antibodies (10%) and an antibody detection limit (25%). These results suggest that while laboratory data are useful for interpreting field samples, there can still be differences due to conditions that were not tested in the laboratory.\n\nImportant noticeThis is a pre-print version of the manuscript, made available through bioRxiv.org. Note that this manuscript has not yet been peer-reviewed, and has been submitted to a peer-reviewed journal.

immunology↗