Mitochondria are dynamic organelles that play crucial roles in energy production, metabolic balance, calcium homeostasis, apoptosis, and innate immunity, and are key determinants of cell fate. They are also targets for viral invasion of the body. Many viral proteins target mitochondria, controlling mitochondrial morphology, metabolism, and immune response, thereby achieving immune evasion, promoting their proliferation, and accelerating the infection process. Mitochondrial quality control is key to maintaining normal physiological functions and mitochondrial homeostasis. Dysregulation of mitochondrial dynamics is closely related to the development of many diseases. New roles of mitochondrial dynamics in viral infection are constantly being discovered. Viruses change mitochondrial dynamics by targeting mitochondria to achieve a persistent state of infection. Currently, understanding of mitochondrial dynamics during viral infection is limited. Research on the impact of viral proteins on mitochondrial dynamics provides a foundation for investigating the pathogenesis of viral infections, the disease process, and identifying potential therapeutic targets. This review focuses on the connection between viral infection and mitochondrial dynamics and priority areas for research on virus-mediated mitochondrial immunity, provides insight into the regulation of mitochondrial dynamics by viruses targeting mitochondria, and explores potential means of mitochondrial-mediated control and treatment of viral diseases.

Zhao L, et al. J Vet Sci. 2021 Aug;22(6):e66. https://doi.org/10.4142/jvs.2021.22.e66

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung tumour caused by the Jaagsiekte Sheep Retrovirus (JSRV). Histopathological diagnosis is the gold standard for OPA diagnosis. However, interpretation of traditional pathology images is complex and operator dependent. The mask regional convolutional neural network (Mask R-CNN) has emerged as a valuable tool in pathological diagnosis. This study utilized 54 typical OPA whole slide images (WSI) to extract 7167 typical lesion images containing OPA to construct a Common Objects in Context (COCO) dataset for OPA pathological images. The dataset was categorized into training and test sets (8:2 ratio) for model training and validation. Mean average specificity (mASp) and average sensitivity (ASe) were used to evaluate model performance. Six WSI-level pathological images (three OPA and three non-OPA images), not included in the dataset, were used for anti-peeking model validation. A random selection of 500 images, not included in the dataset establishment, was used to compare the performance of the model with assessment by pathologists. Accuracy, sensitivity, specificity, and concordance rate were evaluated. The model achieved a mASp of 0.573 and an ASe of 0.745, demonstrating effective lesion detection and alignment with expert annotation. In Anti-Peeking verification, the model showed good performance in locating OPA lesions and distinguished OPA from non-OPA pathological images. In the random 500-image diagnosis, the model achieved 92.8% accuracy, 100% sensitivity, and 88% specificity. The agreement rates between junior and senior pathologists were 100% and 96.5%, respectively. In conclusion, the Mask R-CNN-based OPA diagnostic model developed for OPA facilitates rapid and accurate diagnosis in practical applications.

Duan X, et al. J Vet Sci. 2024 Aug;25:e61. https://doi.org/10.4142/jvs.24158

Ovine pulmonary adenocarcinoma (OPA), caused by the exogenous Jaagsiekte sheep retrovirus (JSRV), shares several pathological and molecular features with human lung adenocarcinoma, providing an important model for comparative oncology. JSRV pathogenesis is mostly studied at the transcriptome level, with systematic proteomic and metabolomic studies remaining insufficient. Therefore, this study aimed to systematically characterise the molecular alterations associated with JSRV-induced OPA by integrating direct data-independent acquisition proteomics and untargeted metabolomics. We established an OPA model by infecting lambs with JSRV and performed multi-omics analyses on the lesion and control lung tissues (n = 3 per group for both proteomic and metabolomic analyses). In total, 1631 differentially expressed proteins and 748 differential metabolites were identified, and the two omics datasets exhibited highly coordinated variations. Integrated analyses suggested that adhesion remodelling (with downregulated LIMCH1), endoplasmic reticulum stress (with upregulated HYOU1), and metabolic and immune-related alterations (accompanied by elevated GFPT1 and PTGS2) represent major biological processes associated with JSRV infection. Western blot analysis confirmed the expression changes in these proteins. Overall, this study provides a multidimensional molecular landscape of OPA and expands current understanding of the molecular alterations associated with JSRV infection. These findings provide candidate pathways and molecular targets for future mechanistic studies and comparative investigations of lung adenocarcinoma.

Background Ovine pulmonary adenomatosis (OPA) is a contagious lung epithelial tumor of sheep caused by jaagsiekte sheep retrovirus (JSRV), which causes severe economic losses for the sheep industry in the world. The specific oncogenic mechanism of JSRV is not yet clarified. Methods In this study, RNA was extracted from lung tissues of 3 naturally infected OPA cases and 3 healthy individuals for transcriptome sequencing (RNA-Seq). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm the sequencing data. Immunohistochemistry (IHC) and western blot (WB) were performed to confirm the signaling pathway enriched by DEGs that was activated in naturally infected OPA cases. Cell viability, wound-healing, transwell and colony formation assays were performed to assess the cell malignant transformation of sheep trophoblast cells (STCs) transformed with JSRV- env lentivirus in vitro, and then WB was performed to confirm the signaling pathway that had been validated in the lung tissues. Results A total of 366 DEGs (154 up-regulated and 212 down-regulated) were identified by RNA-Seq of lung tissues of naturally infected OPA cases and healthy individuals. GO analysis showed that 366 DEGs were significantly enriched in 178 GO terms, including 114 biological processes, 19 cellular components and 45 molecular functions. KEGG analysis showed that the DEGs mainly enriched in cell proliferation, differentiation, apoptosis and migration, such as PI3K/Akt/mTOR, MAPK and Hippo signaling pathway, and Hippo signaling pathway has never been reported in naturally infected OPA cases. qRT-PCR results of 10 DEGs which were selected randomly were consistent with RNA-Seq results. The protein expression of Hippo signaling pathway were up-regulated in naturally infected OPA lung tissues. Cell viability, wound-healing, transwell and colony formation assays confirmed that JSRV- env lentivirus caused malignant transformation of STCs and JSRV Env increased the protein expression of Hippo signaling pathway. Conclusions This research first identified the changes in the transcriptome level of naturally infected OPA lung tissues. These data confirm that the Hippo signaling pathway is involved in the mechanism of OPA, clarify the interaction between Hippo signaling pathway and JSRV Env, provide further evidence for the tumorigenic mechanism of JSRV.