Biology subjects

Mombaerts, P.

Publications and source records attributed to Mombaerts, P..

3 recordsLinked to original sources

bioRxiv2025

Oral 4-fluorouridine completely suppresses epidemic Oropouche virus replication in mice and confers protection against virus-induced disease.

Oropouche virus (OROV) is an orthobunyavirus that causes increasingly frequent and severe outbreaks in Central and South America. We report that 4'-fluorouridine (4'-FlU) inhibits the in vitro replication of epidemic and pre-epidemic OROV strains in multiple cell lines. In vitro polymerase assays demonstrate that 4'-FlU (as its triphosphate) targets the Peribunyaviridae L protein, is incorporated during RNA synthesis and causes premature chain termination. Following 69 consecutive days of in vitro passages of OROV in the presence of suboptimal concentrations of 4'-FlU, no drug-resistant variants were identified in the viral polymerase. In stringent mouse (AG129) or Syrian hamster OROV-infection models, oral administration of 4'-FlU completely blocked viral replication and virus-induced disease, even when administration was delayed until 72 hours after infection. Our findings support exploring the potential of 4'-FlU for the management of OROV infections in humans.

microbiology↗

bioRxiv2019

Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons

Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with over 850 in human and nearly 1500 genes in mouse. The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon.

genomics↗

bioRxiv2019

A transcriptomic atlas of mammalian olfactory mucosae reveals an evolutionary influence on food odor detection in humans

The mammalian olfactory system displays species-specific adaptations to different ecological niches. To investigate the evolutionary dynamics of olfactory sensory neuron (OSN) sub-types across 95 million years of mammalian evolution, we applied RNA-sequencing of whole olfactory mucosa samples from mouse, rat, dog, marmoset, macaque and human. We find that OSN subtypes representative of all known mouse chemosensory receptor gene families are present in all analyzed species. Further, we show that OSN subtypes expressing canonical olfactory receptors (ORs) are distributed across a large dynamic range and that homologous subtypes can be either highly abundant across all species or species/order-specific. Interestingly, highly abundant mouse and human OSN subtypes detect odorants with similar sensory profiles, and sense ecologically relevant odorants, such as mouse semiochemicals or human key food odorants. Taken together, our results allow for a better understanding of the evolution of mammalian olfaction in mammals and provide insights into the possible functions of highly abundant OSN subtypes in mouse and human.

neuroscience↗