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Molecular Evolution and Zoonotic Potential of Muju Virus (Orthohantavirus puumalaense) in Craseomys regulus, Republic of Korea.

Orthohantavirus puumalaense causes hemorrhagic fever with renal syndrome in Europe, with Puumala virus (PUUV) as its primary representative. Muju virus (MUJV), harbored by Craseomys regulus, an Arvicolinae rodent species endemic to the Republic of Korea (ROK), is also a genotype of O. puumalaense. However, their genomic diversity and zoonotic potential remain largely unknown. To investigate their prevalence, 185 voles were collected from 23 regions of the ROK between 2012 and 2023. Serological assays detected anti-PUUV immunoglobulin G antibodies in five samples (3.1%), whereas reverse-transcription polymerase chain reaction confirmed MUJV RNA in identical specimens (2.7%). Amplicon-based nanopore sequencing facilitates near-complete genome recovery, enabling high-resolution comparative analysis. Phylogenetic analysis revealed distinct genetic lineages in Gangwon and Jeollabuk Provinces. Evolutionary rate estimates indicated greater sequence divergence in the S and L segments than in the M segment. A zoonotic risk assessment revealed that most MUJV variants exhibited moderate-to-high spillover potential. The molecular detection of MUJV in Cheorwon, Gangwon Province, expands its known geographic range and provides the first molecular evidence of MUJV circulation in this region. These findings highlight the need for continued surveillance and seroprevalence studies of MUJV to assess its potential for human exposure and public health relevance in the ROK.

Animals

Firemaster 550 differentially alters gene expression underlying synaptic function in amygdala of prairie voles after gestational or lactational exposure.

Neurodevelopmental disorders often share similar behavioral diagnostic criteria including socioemotional and cognitive deficits. The prairie vole is a uniquely suitable model to study these deficits because they demonstrate strong social affiliation, bi-parental care, and partner attachment. Previously, we have shown that developmental exposure to the flame-retardant mixture Firemaster 550 (FM 550) impairs socioemotional behavior in the prairie vole and alters underlying neuroanatomy and function. However, the mechanisms for impaired pair bonding in males and increased anxiety in females remain unknown, along with the specific critical window(s) of vulnerability. Herein, we exposed prairie vole dams to FM 550 during gestation or lactation, and performed bulk RNA-seq on the amygdala, a hub of socioemotional processing, in their adult offspring. Two mathematically orthogonal methods were utilized for analysis, a linear statistical method and an ensemble machine learning method, incorporating sex as a biological variable. Gene ontology (GO) pathway analysis was performed following both and results compared to identify potential mechanisms of toxicity. GO results indicated consistent expression changes in the Synapse cellular component in all conditions, and implicated glutamatergic signaling specifically. Additionally, gestational exposure (GE) altered genes underlying modulation of synaptic transmission and neural development, while lactational exposure (LE) impacted genes underlying synaptic plasticity, axon guidance, and mitophagy. Machine learning identified disruption of endocrine system development, regulation of biosynthetic processes in GE animals, and suppression of various neuroinflammatory genes across multiple groups. Finally, we performed RNA expression analysis using Nanostring and demonstrated stronger correlation with the differentially expressed genes (DEG) of interest in females than males. Overall, this study demonstrates both the intersecting and distinct impacts of FM 550 exposure on amygdalar gene expression depending on sex and timing of exposure.

Animals

A muskrat tissue atlas of small non-coding RNAs and their regulatory roles in muskrat musk secretion.

Muskrat musk, secreted by the male muskrat scent gland during the secretion period, is a valuable natural product with promising pharmacological activities. Its synthesis is regulated not only by coding genes but also by small non-coding RNAs (sncRNAs). However, a comprehensive tissue atlas of sncRNAs in muskrats has been lacking. To address this issue, we systematically profiled the expression levels of 6 sncRNA categories (piRNA [PIWI-interacting RNA], miRNA [microRNA], snoRNA [small nucleolar RNA], snRNA [small nuclear RNA], tRNA [transfer RNA], and other RNAs) across 13 tissues of the muskrat via deep sequencing. We identified 23,957 sncRNAs (∼ 65%) exhibiting tissue-specific expression patterns throughout the body. The results show that miRNA is the main contributor to tissue specificity. Eleven tissues showed a significantly higher number of miRNA-5p arm expressions compared to the 3p arm, although the brain was an exception. Quantitative results imply that miR-477-3p/5p and miR-794-3p are potentially involved in the regulation of muskrat musk synthesis and secretion in the muskrat scent glands. Their target genes were enriched in pathways related to energy supply, lipid metabolism, and cyclic morphological changes of the scent gland. Furthermore, we constructed a set of co-expressed miRNAs based on the hormone-dominated "brain-testis-scent gland" axis and the energy metabolism-dominated "brain-liver-scent gland" axis. These results provide the most comprehensive description to date of tissue-specific and ubiquitous sncRNAs in individual muskrat tissues. We anticipate that these data will enhance the understanding of the molecular regulation underlying muskrat musk synthesis and secretion.

Animals

Transcriptome analysis of brown adipose tissue in Brandt's vole treated with tannic acid under cold exposure.

BACKGROUND: Tannic acid (TA) is a hydrolysable plant secondary metabolite known to influence multiple physiological processes in animals; however, its role in regulating brown adipose tissue (BAT) thermogenesis remains poorly understood. Notably, the overwinter food caches of Brandt's voles predominantly consist of Artemisia species, which are rich in TA. This study aimed to determine whether TA contributes to cold tolerance in Brandt's voles by activating BAT thermogenesis. Adult male voles were administered TA, after which the masses of BAT and inguinal white adipose tissue (iWAT) were measured, and temperature changes in BAT, the body surface, and the rectum were recorded following exposure to - 20 °C. In addition, transcriptomic analyses of BAT were performed, and the expression and protein levels of key thermogenic markers were assessed. RESULTS: The results showed that TA reduced iWAT mass while exerting minimal effects on BAT mass. TA-treated voles exhibited significantly elevated temperatures in BAT, the body surface, and the rectum after cold exposure. Histological analyses revealed that TA treatment reduced adipocyte area in iWAT while increasing the number of nuclei in brown adipocytes in BAT. In BAT, differentially expressed genes (DEGs) in voles receiving a low TA dose were significantly enriched in pathways related to fat digestion and absorption and peroxisome proliferator-activated receptor (PPAR) signaling. In contrast, DEGs in voles administered a high TA dose were predominantly associated with brown adipocyte differentiation and the upregulation of cold-induced thermogenesis. Moreover, TA administration increased the expression of FFAR4 and UCP1, as well as the protein levels of PGC-1α, PPARγ, and UCP1 following cold exposure. CONCLUSIONS: Collectively, these findings demonstrate that TA enhances cold tolerance in Brandt's voles by promoting thermogenic gene expression and stimulating brown adipocyte differentiation in BAT, providing novel insights into the role of plant secondary metabolites in mammalian cold adaptation and herbivore-plant interactions.

Animals

Host hybridization enabled the emergence of a reassorted hantavirus lineage.

The exchange of genetic material between individuals is a key driver of evolution and diversification across most branches of life. Segmented viruses can exchange genetic material through reassortment of genomic segments. New viral strains that emerge from reassortments can have greater infection ranges and higher virulence, although concrete examples of the adaptive advantages of reassortants in nature apart from influenza remain rare. We studied here the evolutionary history and consequences of reassortment in Tula orthohantavirus (TULV) in a hybrid zone between evolutionary lineages of its reservoir host, the common vole (Microtus arvalis). Across 58 trapping sites and 127 infected voles, we detected 27 TULV reassortants in a 12.5 km broad zone at the contact of the parental TULV clades, resembling a viral hybrid zone concordant with the hosts'. Phylogenomic analyses revealed three independent reassortment events, but most of the host hybrid zone was dominated by a single strain with a reassorted M-Segment, which encodes the surface glycoprotein. We detected clade-specific variation in the glycoprotein's N-terminal region consisting of five residues, two of which showed evidence of positive selection. In silico 3D modeling of seven glycoproteins confirmed that this N-terminal region has a unique and specific structure for each TULV clade and the dominant reassortants and is the only structurally variable region of the TULV glycoprotein. Our findings suggest that reassortment between the parental TULV clades in the contact region has resulted in a transgressive virus phenotype potentially adapted to hybrid hosts. This demonstrates the potential of zones of hybridization for the emergence of new virus strains with novel evolutionary trajectories.

Animals