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Species-specific transcriptomic changes upon respiratory syncytial virus infection in cotton rats.

The cotton rat (Sigmodon) is the gold standard pre-clinical small animal model for respiratory viral pathogens, especially for respiratory syncytial virus (RSV). However, without a reference genome or a published transcriptome, studies requiring gene expression analysis in cotton rats are severely limited. The aims of this study were to generate a comprehensive transcriptome from multiple tissues of two species of cotton rats that are commonly used as animal models (Sigmodon fulviventer and Sigmodon hispidus), and to compare and contrast gene expression changes and immune responses to RSV infection between the two species. Transcriptomes were assembled from lung, spleen, kidney, heart, and intestines for each species with a contig N50 > 1600. Annotation of contigs generated nearly 120,000 gene annotations for each species. The transcriptomes of S. fulviventer and S. hispidus were then used to assess immune response to RSV infection. We identified 238 unique genes that are significantly differentially expressed, including several genes implicated in RSV infection (e.g., Mx2, I27L2, LY6E, Viperin, Keratin 6A, ISG15, CXCL10, CXCL11, IRF9) as well as novel genes that have not previously described in RSV research (LG3BP, SYWC, ABEC1, IIGP1, CREB1). This study presents two comprehensive transcriptome references as resources for future gene expression analysis studies in the cotton rat model, as well as provides gene sequences for mechanistic characterization of molecular pathways. Overall, our results provide generalizable insights into the effect of host genetics on host-virus interactions, as well as identify new host therapeutic targets for RSV treatment and prevention.

Animals

Adaptation across an extreme elevational gradient in Andean leaf-eared mice, the world's highest-dwelling mammal.

Andean leaf-eared mice (Phyllotis vaccarum) live at the highest elevations of any mammal, and they also have the broadest elevational range, from sea level to mountain summits of >6700 meters. Highland populations have evolved an enhanced thermogenic capacity in hypoxia relative to lowland conspecifics, and this improved physiological performance is associated with an increased mitochondrial respiratory capacity in skeletal muscle. Population genomic analyses identified mechanisms of hypoxia adaptation and revealed an unanticipated dimension of environmental adaptation in P. vaccarum because selection on biotransformation pathways suggests an evolved capacity to metabolize plant-derived dietary toxins. The world's highest-dwelling mammal has adapted to habitats at both the low- and high-elevation limits of its range, and much of the elevation-related selection relates to previously unappreciated aspects of feeding ecology.

Animals

Diet change reveals asymmetric response in gene expression and microbial composition across the digestive tract of two closely related herbivores.

BACKGROUND: Understanding what shapes variation in organisms' capacity to utilize novel resources is essential to predicting how species will respond to environmental change. For herbivores, exposure to toxic phytochemicals in novel plants may limit persistence in new habitats. We investigated the behavioral, physiological, genetic, and microbial consequences of diet switching in two closely related species of rodent herbivores that each consume differentially toxic plants in their native habitat, and that maintain different dietary strategies (i.e., relative dietary specialist versus relative generalist). RESULTS: In reciprocal laboratory feeding trials, we exposed wild-caught woodrats (genus Neotoma) to toxins characteristic of either familiar or novel plant secondary compounds. We measured changes in food and water intake, locomotor activity, gut microbial composition, and gene expression across the digestive tract following feeding trials. The dietary generalist responded minimally, but the specialist responded strongly when exposed to the novel diet. This response included behavioral and genetic components including increased water intake, reduction in locomotor activity, increased differential expression of detoxification genes, and a greater shift in gut microbial composition. CONCLUSIONS: The dietary specialist exhibited a strong response to diet switching that corresponded with ecologically relevant shifts in behavior and physiology that would have negative fitness consequences. Although the dietary specialist had a strong genetic and microbial response to novel plant secondary compounds, this response would likely be insufficient to overcome the immediate challenge of exposure to novel dietary toxins in the wild. Our results underscore the link between feeding strategy and the capacity to shift to novel dietary resources in response to environmental change.

Animals

Genetic analysis of Schistosoma mansoni in a low-transmission area in Brazil suggests population sharing between wild-hosts and humans and geographical isolation.

BACKGROUND: The fluke Schistosoma mansoni is the causative agent of intestinal schistosomiasis, a neglected tropical disease, and remains prevalent in certain regions of Brazil. In the municipality of Sumidouro, state of Rio de Janeiro, Brazil, a low-endemic area for S. mansoni, water rats (Nectomys squamipes) are naturally infected by this trematode. The S. mansoni populations infecting humans and water-rats in Sumidouro exhibit distinct patterns of cercarial emergence (chronotypes) and phenotypic differences between hosts. Previous studies have shown that the adaptation of S. mansoni populations to human hosts (diurnal chronotype) and water rats (nocturnal chronotype) could result in prezygotic isolation. To test this hypothesis, we employed the mitochondrial cytochrome c oxidase subunit 1 gene (MT-CO1) and microsatellite loci as genetic markers. PRINCIPAL FINDINGS: We assessed the population structure between the definitive host species and geographically distant isolates collected from two endemic localities (Pamparrão-PAM and Encanto-Soledade-ENC-SOL) in Sumidouro. Additionally, we evaluated the phylogenetic relationships between S. mansoni from Sumidouro and those from other countries. Five haplotypes of the MT-CO1 gene were identified, with haplotypes 3 and 4 exclusive to ENC-SOL, and haplotypes 1, 2, and 3 were shared between humans and water rats. Haplotype 1 was also shared with other Brazilian localities, South American countries and a single locality in West Africa. The remaining haplotypes were exclusive to Sumidouro, indicating local genetic diversity. Population structure analysis revealed no genetic differentiation associated with host species but rather geographical structuring, probably due to the sedentary habits of rodents and the limited movement of humans between localities. This finding indicates that S. mansoni populations with different chronotypes are not genetically isolated and that significant gene flow occurs between them. CONCLUSIONS: In conclusion, our findings confirm that wild rodents contribute to the maintenance of the S. mansoni life cycle in Sumidouro and can serve as indicators of local transmission hotspots.

Animals