Overcoming the Barrier of the Respiratory Epithelium during Canine Distemper Virus Infection

Shin, Dai‐Lun; Chludzinski, Elisa; Wu, Nan-Lin; Peng, Jen‐Kuei; Ciurkiewicz, Małgorzata; Sawatsky, Bevan; Pfaller, Christian K.; Baechlein, Christine; Messling, Véronika von; Haas, Ludwig; Beineke, Andreas; Herrler, Georg

doi:10.1128/mbio.03043-21

Cited by 7 publications

(4 citation statements)

References 70 publications

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“…The second epithelial receptor, the nectin cell adhesion molecule-4 (NECTIN-4), is a component of adherens junctions of epithelial cells. In various studies on the formation of syncytia, it has been reported that SLAM and NECTIN-4 receptors, which allow the virus to enter the cell, facilitate the cell to cell spread and are effective in the formation of syncytia (Rendon Marin et al, 2019;Shin et al, 2022). It has also been reported that morbilliviruses inhibit the JAK/STAT signaling pathway, affecting the natural immunity, and being particularly important in the entry of the virus into the respiratory tract epithelial cells, spreading from cell to cell, and syncytia formation (Shin et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…In various studies on the formation of syncytia, it has been reported that SLAM and NECTIN-4 receptors, which allow the virus to enter the cell, facilitate the cell to cell spread and are effective in the formation of syncytia (Rendon Marin et al, 2019;Shin et al, 2022). It has also been reported that morbilliviruses inhibit the JAK/STAT signaling pathway, affecting the natural immunity, and being particularly important in the entry of the virus into the respiratory tract epithelial cells, spreading from cell to cell, and syncytia formation (Shin et al, 2022). The presence of characteristic eosinophilic inclusions, frequently cytoplasmic but occasionally intranuclear, in the epithelial tissue, as well as intracytoplasmic inclusions less frequently in the CNS has also been documented (Maxie, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Pathological and molecular investigation of canine distemper virus: Phylogenetic analysis of co-circulating genetic lineages in Türkiye

Karapınar

İlhan

Usta

et al. 2023

AVet

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Canine distemper virus (CDV) is a highly contagious virus that infects a wide variety of animals of carnivore species and may cause manifestations from subclinical infection to fatal disease. In this study, dogs clinically suspected having distemper were examined by reverse transcriptase-polymerase chain reaction (RT-PCR), histopathology and immuno-histochemistry. By histopathological examination, characteristic intracytoplasmic and/or intranuclear inclusion bodies were observed in the lung, stomach, small intestine, liver, kidney, spleen and central nervous system. Interstitial and broncho-interstitial pneumonia, gastroenteritis and encephalitis were revealed. CDV antigens were detected in all tissues with characteristic histopathological findings. The antigens were more abundant in the bronchial and bronchiolar epithelium and in the syntitial cells. Phylogenetic analyses were performed using the PCR-amplified partial sequences of the genes encoding the viral heamagglutinin and fusion proteins. The phylogenetic trees showed that the newly determined sequences were diverse and clustered within different lineages of the European or the Arctic strains.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pathological and molecular investigation of canine distemper virus: Phylogenetic analysis of co-circulating genetic lineages in Türkiye

Karapınar

İlhan

Usta

et al. 2023

AVet

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“…Taken together, these findings are comparable with analyses of IFN-related genes during natural CDV infection in the canine CNS [ 55 , 139 ]. In CDV-infected canine air–liquid interface cultures, an induced disturbance of interferon signaling by blockage of the interferon-induced JAK/STAT pathway enhanced cytopathic effects and facilitated viral spread, underlining the important role of type I interferons in the defense against respiratory CDV infection [ 153 ]. These results highlight the potential of interferon-based antiviral therapy in CDV infection, as shown by in vitro studies [ 154 ].…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and Transcriptional Changes of Pulmonary Immune Responses in Dogs Following Canine Distemper Virus Infection

Chludzinski¹,

Klemens²,

Ciurkiewicz³

et al. 2022

IJMS

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Canine distemper virus (CDV), a morbillivirus within the family Paramyxoviridae, is a highly contagious infectious agent causing a multisystemic, devastating disease in a broad range of host species, characterized by severe immunosuppression, encephalitis and pneumonia. The present study aimed at investigating pulmonary immune responses of CDV-infected dogs in situ using immunohistochemistry and whole transcriptome analyses by bulk RNA sequencing. Spatiotemporal analysis of phenotypic changes revealed pulmonary immune responses primarily driven by MHC-II+, Iba-1+ and CD204+ innate immune cells during acute and subacute infection phases, which paralleled pathologic lesion development and coincided with high viral loads in CDV-infected lungs. CD20+ B cell numbers initially declined, followed by lymphoid repopulation in the advanced disease phase. Transcriptome analysis demonstrated an increased expression of transcripts related to innate immunity, antiviral defense mechanisms, type I interferon responses and regulation of cell death in the lung of CDV-infected dogs. Molecular analyses also revealed disturbed cytokine responses with a pro-inflammatory M1 macrophage polarization and impaired mucociliary defense in CDV-infected lungs. The exploratory study provides detailed data on CDV-related pulmonary immune responses, expanding the list of immunologic parameters potentially leading to viral elimination and virus-induced pulmonary immunopathology in canine distemper.

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“…In veterinary medicine, it is known that canine distemper virus uses nectin‐4 as a receptor (Shin et al., 2022), and furthermore, it has been reported that nectin‐4 expression is involved in tumour growth in prostate cancer (Salda et al., 2019). However, to our knowledge, no studies have examined the expression of Nectin‐4 in CPLA.…”

Section: Introductionmentioning

confidence: 99%

Gene expression ofNectin‐4and its clinical significance in dogs with primary lung adenocarcinoma

Tamura

Ishigaki

Yoshida

et al. 2022

Veterinary Medicine & Sci

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Background Canine primary lung adenocarcinoma (CPLA) is suspected by radiography or computed tomography; however, since there are no tumour markers, early diagnosis is difficult, and the prognosis is poor due to increased tumour volume. Nectin‐4 has been reported to be expressed in human lung, ovarian, and pancreatic cancers and promotes tumour growth. It has been reported to be a tumour marker and prognostic factor, and oncolytic virotherapy is being investigated using nectin‐4 as a therapeutic target. Objectives The purpose of this study was to investigate the expression of Nectin‐4 in CPLA and its clinical significance in dogs with pulmonary adenocarcinomas. Methods The relationships between Nectin‐4 expression and signalling, tumour volume, tumour weight, and prognosis were analyzed in 34 CPLA patients. Results The expression of canine Nectin‐4 (high Nectin‐4) was found in 25 of 34 cases (73%), and Nectin‐4 expression levels did not show any significant associations with gender, body weight, and tumour stage. However, there was a significant positive correlation between Nectin‐4 expression and tumour volume (r = 0.623, p < 0.05) and tumour weight (r = 0.735, p < 0.05). Regarding prognosis, the median survival time was 427 days in high Nectin‐4 cases and 420 days in cases with no Nectin‐4 expression. Conclusion Our study demonstrated that Nectin‐4 is highly expressed in CPLA. In addition, nectin‐4 might be a tumour growth factor in CPLA and thus is a promising biomarker for CPLA. Further investigations on nectin‐4 in CPLA are warranted for its diagnosis and novel targets for oncolytic virotherapy.

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Overcoming the Barrier of the Respiratory Epithelium during Canine Distemper Virus Infection

Cited by 7 publications

References 70 publications

Pathological and molecular investigation of canine distemper virus: Phylogenetic analysis of co-circulating genetic lineages in Türkiye

Pathological and molecular investigation of canine distemper virus: Phylogenetic analysis of co-circulating genetic lineages in Türkiye

Phenotypic and Transcriptional Changes of Pulmonary Immune Responses in Dogs Following Canine Distemper Virus Infection

Gene expression ofNectin‐4and its clinical significance in dogs with primary lung adenocarcinoma

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