Integrated Analysis of Differentially Expressed miRNAs and mRNAs in Goat Skin Fibroblast Cells in Response to Orf Virus Infection Reveals That cfa-let-7a Regulates Thrombospondin 1 Expression

Pang, Feng; Wang, Xinying; Chen, Zhen; Zhang, Zhenxing; Zhang, Mengmeng; Wang, Chengqiang; Yang, Xiaohong; An, Q.; Du, Lijun; Wang, Fengyang

doi:10.3390/v12010118

Cited by 8 publications

(7 citation statements)

References 56 publications

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“…Previous studies have analyzed transcriptome data of ORFV-infected host cells and characterized gene expression changes in host cells after ORFV infection ( 39 , 40 ). However, there are few data on the transcriptome of virus and host and the interaction between virus and host after the infection of host cells with ORFV virulent and attenuated strains by RNA sequencing technology.…”

Section: Discussionmentioning

confidence: 99%

Dual analysis of wild-type and attenuated Orf virus and host cell transcriptomes revealed novel virus-host cell interactions

Yao,

Jing,

Geng

et al. 2023

mSphere

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The attenuated Orf virus (ORFV) strain (aFX0910), derived from continuous passages of wild-type strain FX0910 in vitro , displays obviously lower virulence in kids. However, the latent virulence determinants and intracellular mechanisms for the attenuated variant remain unknown. In this study, we constructed a comprehensive analysis of the ORFV and goat lip fibroblasts transcriptomes during viral infection using RNA sequencing. Focusing on the host transcriptome, we performed gene expression analysis, Gene Ontology analysis, and biological pathway analysis, among others. This integrated analysis allowed us to assess potential changes in mRNA expression and single nucleotide polymorphisms (SNPs) in both viral and host genes. In general, the global patterns of immune gene expression induced by different ORFV isolates were mostly shared. However, host transcripts and non-synonymous of viral genes differed between the wild-type and attenuated ORFV strains. Notably, the natural ORFV isolate (FX0910) predominantly triggered an innate immune response in host cells, while aFX0910 downregulated innate immune response and antiviral response. Analysis of viral transcriptomes manifested that FX0910 and aFX0910 had different SNP events in multiple functional genes. Collectively, our findings highlighted novel insights into virus-host interactions and shed light on the molecular basis of ORFV virulence at the genomic level. Furthermore, this study may contribute to the development of targeted intervention strategies and the advancement of vaccine research in the field of ORFV. IMPORTANCE Currently, the only available commercial vaccines for Orf virus (ORFV) are live attenuated vaccines, which present a potential risk of reversion to virulence. Therefore, understanding the pathogenic mechanisms of different virulent strains of ORFV and host immune responses triggered by these viruses is crucial for developing new vaccines and interventions. In this study, we found that the attenuated strain downregulates the host innate immune response and antiviral activity. In addition, we noted that the wild-type strain can induce the immune response pattern centered on interferon-stimulated genes and interferon regulatory factor gene family. We predicted that STAT1 and STAT2 are the main transcription factors upstream of target gene promoters through gene regulatory networks and exert significant regulatory effects on co-expressed genes. Our study elucidated the complex interaction between ORFV strains and host cell immune responses, providing new insights into vaccine research for ORFV.

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Section: Discussionmentioning

confidence: 99%

Dual analysis of wild-type and attenuated Orf virus and host cell transcriptomes revealed novel virus-host cell interactions

Yao,

Jing,

Geng

et al. 2023

mSphere

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“…ovary [ 45 ], liver [ 46 ], pituitary [ 47 ], lung [ 48 ]) and types of cells (e.g. skeletal muscle satellite cells [ 49 ], skin fibroblast cells [ 50 ], Leydig cells [ 51 ], blood leukocytes and milk somatic cells [ 52 ], intramuscular preadipocytes [ 53 ], endometrial epithelium cells [ 54 ]) in physiological and pathological processes in goats, including in response to infectious diseases. For example, the expression of 316 DEmiRNAs was found in peripheral blood mononuclear cells of goats infected with peste des petits ruminants virus, and most of the predicted targets of these DEmiRNAs were found to be involved in immune escape [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Temporal transcriptomic changes in microRNAs involved in the host immune response and metabolism during Neospora caninum infection

et al. 2023

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Background Neospora caninum infection is a major cause of abortion in cattle, which results in serious economic losses to the cattle industry. However, there are no effective drugs or vaccines for the control of N. caninum infections. There is increasing evidence that microRNAs (miRNAs) are involved in many physiological and pathological processes, and dysregulated expression of host miRNAs and the biological implications of this have been reported for infections by various protozoan parasites. However, to our knowledge, there is presently no published information on host miRNA expression during N. caninum infection. Methods The expression profiles of miRNAs were investigated by RNA sequencing (RNA-seq) in caprine endometrial epithelial cells (EECs) infected with N. caninum at 24 h post infection (pi) and 48 hpi, and the functions of differentially expressed (DE) miRNAs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The transcriptome data were validated by using quantitative real-time polymerase chain reaction. One of the upregulated DEmiRNAs, namely chi-miR-146a, was selected to study the effect of DEmiRNAs on the propagation of N. caninum tachyzoites in caprine EECs. Results RNA-seq showed 18 (17 up- and one downregulated) and 79 (54 up- and 25 downregulated) DEmiRNAs at 24 hpi and 48 hpi, respectively. Quantitative real-time polymerase chain reaction analysis of 13 randomly selected DEmiRNAs (10 up- and three downregulated miRNAs) confirmed the validity of the RNA-seq data. A total of 7835 messenger RNAs were predicted to be potential targets for 66 DEmiRNAs, and GO and KEGG enrichment analysis of these predicted targets revealed that DEmiRNAs altered by N. caninum infection may be involved in host immune responses (e.g. Fc gamma R-mediated phagocytosis, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, transforming growth factor-β signaling pathway, mitogen-activated protein kinase signaling pathway) and metabolic pathways (e.g. lysine degradation, insulin signaling pathway, AMP-activated protein kinase signaling pathway, Rap1 signaling pathway, calcium signaling pathway). Upregulated chi-miR-146a was found to promote N. caninum propagation in caprine EECs. Conclusions This is, to our knowledge, the first report on the expression profiles of host miRNAs during infection with N. caninum, and shows that chi-miR-146a may promote N. caninum propagation in host cells. The novel findings of the present study should help to elucidate the interactions between host cells and N. caninum. Graphical Abstract

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“…The integrity of total RNA was analyzed by an Agilent 2100 bioanalyzer (Agilent Technologies, Santa Clara, CA, USA), and RNA integrity number (RIN) >7 was used for NGS. The concentration of total RNA was detected by NanoDrop™ 2000 (Thermo Fisher Scientific) ( Pang et al, 2020 ). As described previously, miRNA sequencing was performed on the Illumina HiSeq 2500 platform from LC Sciences (Hangzhou, China) ( Pang et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats

Lai

Zhao

Zhuang

et al. 2022

PeerJ

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Background In the bone marrow microenvironment of postmenopausal osteoporosis (PMOP), bone marrow mesenchymal stem cell (BMSC)-derived exosomal miRNAs play an important role in bone formation and bone resorption, although the pathogenesis has yet to be clarified. Methods BMSC-derived exosomes from ovariectomized rats (OVX-Exo) and sham-operated rats (Sham-Exo) were co-cultured with bone marrow-derived macrophages to study their effects on osteoclast differentiation. Next-generation sequencing was utilized to identify the differentially expressed miRNAs (DE-miRNAs) between OVX-Exo and Sham-Exo, while target genes were analyzed using bioinformatics. The regulatory effects of miR-27a-3p and miR-196b-5p on osteogenic differentiation of BMSCs and osteoclast differentiation were verified by gain-of-function and loss-of-function analyses. Results Osteoclast differentiation was significantly enhanced in the OVX-Exo treatment group compared to the Sham-Exo group. Twenty DE-miRNAs were identified between OVX-Exo and Sham-Exo, among which miR-27a-3p and miR-196b-5p promoted the expressions of osteogenic differentiation markers in BMSCs. In contrast, knockdown of miR-27a-3p and miR-196b-5p increased the expressions of osteoclastic markers in osteoclast. These 20 DE-miRNAs were found to target 11435 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these target genes were involved in several biological processes and osteoporosis-related signaling pathways. Conclusion BMSC-derived exosomal miR-27a-3p and miR-196b-5p may play a positive regulatory role in bone remodeling.

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Integrated Analysis of Differentially Expressed miRNAs and mRNAs in Goat Skin Fibroblast Cells in Response to Orf Virus Infection Reveals That cfa-let-7a Regulates Thrombospondin 1 Expression

Cited by 8 publications

References 56 publications

Dual analysis of wild-type and attenuated Orf virus and host cell transcriptomes revealed novel virus-host cell interactions

Dual analysis of wild-type and attenuated Orf virus and host cell transcriptomes revealed novel virus-host cell interactions

Temporal transcriptomic changes in microRNAs involved in the host immune response and metabolism during Neospora caninum infection

BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats

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