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1,538 result(s) for "Ruminants - genetics"
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Genetic analyses and functional validation of ruminant SLAMs reveal potential hosts for PPRV
Peste des petits ruminants (PPR), caused by the peste des petits ruminants virus (PPRV), is a highly contagious disease affecting ruminants. While goats and sheep are well-known hosts, PPRV has also spread to wild ruminants, and it remains unclear which ruminant species can be infected. SLAM (Signaling lymphocytic activation molecule) acts as the primary receptor for PPRV, playing a crucial role in the viral infection process. Identifying which ruminant SLAMs can mediate PPRV infection is essential for understanding the potential hosts of PPRV, which is vital for effective eradication efforts. In this study, we first extracted 77 ruminant species’ SLAM sequences from ruminant genome database. Based on these sequences, we predicted the structures of ruminant SLAMs. The analysis revealed that SLAM conformation is similar across ruminant species, and the potential PPRV H protein binding domain residues were conserved among SLAMs of these 77 species. Phylogenetic analysis of SLAM grouped ruminants into six families. We then selected representative SLAMs from each ruminant family to assess their role in PPRV infection. Our findings demonstrated that ruminant SLAMs efficiently mediated PPRV infection, with enhanced viral amplification observed in cells expressing SLAM from java mouse deer ( Tragulidae ) and goat ( Bovidae ), compared to cells expressing SLAM from white tailed deer ( Cervidae ) and giraffe ( Giraffidae ). These results underscore the need to consider a broader range of potential host populations beyond goat and sheep in efforts to prevent and eradicate PPRV.
Immunization With Bovine Herpesvirus-4-Based Vector Delivering PPRV-H Protein Protects Sheep From PPRV Challenge
The Morbillivirus peste des petits ruminants virus (PPRV) is the causal agent of a highly contagious disease that mostly affects sheep and goats and produces considerable losses in developing countries. Current PPRV control strategies rely on live-attenuated vaccines, which are not ideal, as they cannot differentiate infected from vaccinated animals (DIVA). Recombinant vector-based vaccines expressing viral subunits can provide an alternative to conventional vaccines, as they can be easily paired with DIVA diagnostic tools. In the present work, we used the bovine herpesvirus-4-based vector (BoHV-4-A) to deliver PPRV hemagglutinin H antigen (BoHV-4-A-PPRV-H-ΔTK). Vaccination with BoHV-4-A-PPRV-H-ΔTK protected sheep from virulent PPRV challenge and prevented virus shedding. Protection correlated with anti-PPRV IgGs, neutralizing antibodies and IFN-γ-producing cells induced by the vaccine. Detection of antibodies exclusively against H-PPRV in animal sera and not against other PPRV viral proteins such as F or N could serve as a DIVA diagnostic test when using BoHV-4-A-PPRV-H-ΔTK as vaccine. Our data indicate that BoHV-4-A-PPRV-H-ΔTK could be a promising new approach for PPRV eradication programs.
A comparative phylogenomic analysis of peste des petits ruminants virus isolated from wild and unusual hosts
Peste des petits ruminants virus (PPRV) infects a wide range of domestic and wild ruminants, and occasionally unusual hosts such as camel, cattle and pig. Given their broad host-spectrum and disease endemicity in several developing countries, it is imperative to elucidate the viral evolutionary insights for their dynamic pathobiology and differential host-selection. For this purpose, a dataset of all available (n = 37) PPRV sequences originating from wild and unusual hosts was composed and in silico analysed. Compared to domestic small ruminant strains of same geographical region, phylogenomic and residue analysis of PPRV sequences originating from wild and unusual hosts revealed a close relationship between strains. A lack of obvious difference among the studied sequences and deduced residues suggests that these are the host factors that may play a role in their susceptibility to PPRV infection, immune response, pathogenesis, excretion patterns and potential clinical signs or resistance to clinical disease. Summarizing together, the comparative analysis enhances our understanding towards molecular epidemiology of the PPRV in wild and unusual hosts for appropriate intervention strategies particularly at livestock-wildlife interface.
RNAseq Reveals the Contribution of Interferon Stimulated Genes to the Increased Host Defense and Decreased PPR Viral Replication in Cattle
Peste des petits ruminants virus (PPRV) is known to replicate in a wide variety of ruminants causing very species-specific clinical symptoms. Small ruminants (goats and sheep) are susceptible to disease while domesticated cattle and buffalo are dead-end hosts and do not display clinical symptoms. Understanding the host factors that influence differential pathogenesis and disease susceptibility could help the development of better diagnostics and control measures. To study this, we generated transcriptome data from goat and cattle peripheral blood mononuclear cells (PBMC) experimentally infected with PPRV in-vitro. After identifying differentially expressed genes, we further analyzed these immune related pathway genes using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and selected candidate genes were validated using in-vitro experiments. Upon PPRV infection, we identified 12 and 22 immune related genes that were differentially expressed in goat and cattle respectively. In both species, this included the interferon stimulated genes (ISGs) IFI44, IFI6, IFIT1, IFIT2, IFIT3, ISG15, Mx1, Mx2, OAS1X, RSAD2, IRF7, DDX58 and DHX58 that were transcribed significantly higher in cattle. PPRV replication in goat PBMCs significantly increased the expression of phosphodiesterase 12 (PDE12), a 2′,5′-oligoadenylate degrading enzyme that contributes to the reduced modulation of interferon-regulated gene targets. Finally, a model is proposed for the differential susceptibility between large and small ruminants based on the expression levels of type-I interferons, ISGs and effector molecules.
A comprehensive global perspective on phylogenomics and evolutionary dynamics of Small ruminant morbillivirus
A string of complete genome sequences of Small ruminant morbillivirus (SRMV) have been reported from different parts of the globe including Asia, Africa and the Middle East. Despite individual genome sequence-based analysis, there is a paucity of comparative genomic and evolutionary analysis to provide overarching and comprehensive evolutionary insights. Therefore, we first enriched the existing database of complete genome sequences of SRMVs with Pakistan-originated strains and then explored overall nucleotide diversity, genomic and residue characteristics, and deduced an evolutionary relationship among strains representing a diverse geographical region worldwide. The average number of pairwise nucleotide differences among the whole genomes was found to be 788.690 with a diversity in nucleotide sequences (0.04889 ± S.D. 0.00468) and haplotype variance (0.00001). The RNA-dependent-RNA polymerase ( L ) gene revealed phylogenetic relationship among SRMVs in a pattern similar to those of complete genome and the nucleoprotein ( N ) gene. Therefore, we propose another useful molecular marker that may be employed for future epidemiological investigations. Based on evolutionary analysis, the mean evolution rate for the complete genome, N , P , M , F , H and L genes of SRMV was estimated to be 9.953 × 10 –4 , 1.1 × 10 –3 , 1.23 × 10 –3 , 2.56 × 10 –3 , 2.01 × 10 –3 , 1.47 × 10 –3 and 9.75 × 10 –4 substitutions per site per year, respectively. A recombinant event was observed in a Pakistan-originated strain (KY967608) revealing Indian strains as major (98.1%, KR140086) and minor parents (99.8%, KT860064). Taken together, outcomes of the study augment our knowledge and current understanding towards ongoing phylogenomic and evolutionary dynamics for better comprehensions of SRMVs and effective disease control interventions.
Regulation of rumen development in neonatal ruminants through microbial metagenomes and host transcriptomes
Background In ruminants, early rumen development is vital for efficient fermentation that converts plant materials to human edible food such as milk and meat. Here, we investigate the extent and functional basis of host-microbial interactions regulating rumen development during the first 6 weeks of life. Results The use of microbial metagenomics, together with quantification of volatile fatty acids (VFAs) and qPCR, reveals the colonization of an active bacterial community in the rumen at birth. Colonization of active complex carbohydrate fermenters and archaea with methyl-coenzyme M reductase activity was also observed from the first week of life in the absence of a solid diet. Integrating microbial metagenomics and host transcriptomics reveals only 26.3% of mRNA transcripts, and 46.4% of miRNAs were responsive to VFAs, while others were ontogenic. Among these, one host gene module was positively associated with VFAs, while two other host gene modules and one miRNA module were negatively associated with VFAs. Eight host genes and five miRNAs involved in zinc ion binding-related transcriptional regulation were associated with a rumen bacterial cluster consisting of Prevotella , Bacteroides , and Ruminococcus . Conclusion This three-way interaction suggests a potential role of bacteria-driven transcriptional regulation in early rumen development via miRNAs. Our results reveal a highly active early microbiome that regulates rumen development of neonatal calves at the cellular level, and miRNAs may coordinate these host-microbial interactions.
Large-scale ruminant genome sequencing provides insights into their evolution and distinct traits
Ruminants are a diverse group of mammals that includes families containing well-known taxa such as deer, cows, and goats. However, their evolutionary relationships have been contentious, as have the origins of their distinctive digestive systems and headgear, including antlers and horns (see the Perspective by Ker and Yang). To understand the relationships among ruminants, L. Chen et al. sequenced 44 species representing 6 families and performed a phylogenetic analysis. From this analysis, they were able to resolve the phylogeny of many genera and document incomplete lineage sorting among major clades. Interestingly, they found evidence for large population reductions among many taxa starting at approximately 100,000 years ago, coinciding with the migration of humans out of Africa. Examining the bony appendages on the head—the so-called headgear—Wang et al. describe specific evolutionary changes in the ruminants and identify selection on cancer-related genes that may function in antler development in deer. Finally, Lin et al. take a close look at the reindeer genome and identify the genetic basis of adaptations that allow reindeer to survive in the harsh conditions of the Arctic. Science , this issue p. eaav6202 , p. eaav6335 , p. eaav6312 ; see also p. 1130 Ruminant phylogeny is resolved with representative genomes. The ruminants are one of the most successful mammalian lineages, exhibiting morphological and habitat diversity and containing several key livestock species. To better understand their evolution, we generated and analyzed de novo assembled genomes of 44 ruminant species, representing all six Ruminantia families. We used these genomes to create a time-calibrated phylogeny to resolve topological controversies, overcoming the challenges of incomplete lineage sorting. Population dynamic analyses show that population declines commenced between 100,000 and 50,000 years ago, which is concomitant with expansion in human populations. We also reveal genes and regulatory elements that possibly contribute to the evolution of the digestive system, cranial appendages, immune system, metabolism, body size, cursorial locomotion, and dentition of the ruminants.
Genetic basis of ruminant headgear and rapid antler regeneration
Ruminants are a diverse group of mammals that includes families containing well-known taxa such as deer, cows, and goats. However, their evolutionary relationships have been contentious, as have the origins of their distinctive digestive systems and headgear, including antlers and horns (see the Perspective by Ker and Yang). To understand the relationships among ruminants, L. Chen et al. sequenced 44 species representing 6 families and performed a phylogenetic analysis. From this analysis, they were able to resolve the phylogeny of many genera and document incomplete lineage sorting among major clades. Interestingly, they found evidence for large population reductions among many taxa starting at approximately 100,000 years ago, coinciding with the migration of humans out of Africa. Examining the bony appendages on the head—the so-called headgear—Wang et al. describe specific evolutionary changes in the ruminants and identify selection on cancer-related genes that may function in antler development in deer. Finally, Lin et al. take a close look at the reindeer genome and identify the genetic basis of adaptations that allow reindeer to survive in the harsh conditions of the Arctic. Science , this issue p. eaav6202 , p. eaav6335 , p. eaav6312 ; see also p. 1130 The genes underlying the development of bony antlers and horns in ruminants are examined. Ruminants are the only extant mammalian group possessing bony (osseous) headgear. We obtained 221 transcriptomes from bovids and cervids and sequenced three genomes representing the only two pecoran lineages that convergently lack headgear. Comparative analyses reveal that bovid horns and cervid antlers share similar gene expression profiles and a common cellular basis developed from neural crest stem cells. The rapid regenerative properties of antler tissue involve exploitation of oncogenetic pathways, and at the same time some tumor suppressor genes are under strong selection in deer. These results provide insights into the evolutionary origin of ruminant headgear as well as mammalian organ regeneration and oncogenesis.
Genetic Characterization of a Novel Mutant of Peste Des Petits Ruminants Virus Isolated from Capra ibex in China during 2015
Peste des petits ruminants virus (PPRV) is the causative agent of peste des petits ruminants (PPR). The spread of PPR often causes severe economic losses. Therefore, special attention should be paid to the surveillance of PPR emergence, spread, and geographic distribution. Here we describe a novel mutant of PPRV China/XJBZ/2015 that was isolated from Capra ibex in Xinjiang province in China 2015. The sequence analysis and phylogenetic assessment indicate that China/XJBZ/2015 belongs to lineage IV, being closely related to China/XJYL/2013 strain. Interestingly, the V protein sequence of China/XJBZ/2015 showed lower homology with other Chinese PPRVs isolated during 2013 to 2014 (94%~95%), whereas it shared 100% identity with three Tibet strains isolated in China 2007. The 3′ UTR, V gene, and C gene were determined to be highly variable. Besides, 29 PPR genomic sequences available in GenBank were analyzed in this study. It is the first time to use PPRV genomic sequences to classify the different lineages which confirmed the lineage clustering of PPRVs using N gene 255 bp fragments and F gene 322 bp fragments. In conclusion, our findings indicate that the PPRVs continue to evolve in China, and some new mutations have emerged.
Genome characterization and phylogenetic analysis of a lineage IV peste des petits ruminants virus in southern China
Since 2013, the second outbreak of peste des petits ruminants (PPR) caused by Peste des petits ruminants virus (PPRV) has spread over more than 20 provinces, municipalities, and autonomous regions in China, resulting in major economic losses for livestock industry. In 2014, we encountered a clinical PPR case on a goat farm in Guangdong province, southern China. The complete genome of this PPRV strain, named CH/GDDG/2014, was sequenced to determine its similarities and differences with other strains. The CH/GDDG/2014 genome comprised 15,954 nucleotides (six nucleotides more than classical PPRVs identified before 2013, but complying with the rule of six) with six open reading frames encoding nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin, and large polymerase protein, respectively. The whole-genome-based alignment analysis indicated that CH/GDDG/2014 had the most proximate consensus (99.8 %) to China/XJYL/2013 and the least consensus (87.2 %) to KN5/2011. The phylogenetic analysis showed that CH/GDDG/2014 was clustered in one branch (lineage IV) with other emerging strains during the second outbreak. This study is the first report describing the whole-genome sequence of PPRV in Guangdong province, southern China and also suggests the PPR outbreak may be closely related to illegal cross-regional importation of goats.