Cell entry of bovine respiratory syncytial virus through clathrin-mediated endocytosis is regulated by PI3K-Akt and Src-JNK pathways

Yang Liu; Dongliang Yang; Wen Jiang; Tianying Chi; Jingli Kang; Zhiliang Wang; Faxing Wu

doi:10.3389/fmicb.2024.1393127

Cell entry of bovine respiratory syncytial virus through clathrin-mediated endocytosis is regulated by PI3K-Akt and Src-JNK pathways

Front Microbiol. 2024 Apr 16:15:1393127. doi: 10.3389/fmicb.2024.1393127. eCollection 2024.

Authors

Yang Liu^#¹, Dongliang Yang^#², Wen Jiang¹, Tianying Chi¹, Jingli Kang¹, Zhiliang Wang¹, Faxing Wu¹

Affiliations

¹ Key Laboratory of Animal Biosafety Risk Prevention and Control of Ministry of Agriculture and Rural Affairs (South), China Animal Health and Epidemiology Center, Qingdao, Shandong, China.
² Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou, Gansu, China.

^# Contributed equally.

Abstract

Bovine respiratory syncytial virus (BRSV) is an RNA virus with envelope that causes acute, febrile, and highly infectious respiratory diseases in cattle. However, the manner and mechanism of BRSV entry into cells remain unclear. In this study, we aimed to explore the entry manner of BRSV into MDBK cells and its regulatory mechanism. Our findings, based on virus titer, virus copies, western blot and IFA analysis, indicate that BRSV enters MDBK cells through endocytosis, relying on dynamin, specifically via clathrin-mediated endocytosis rather than caveolin-mediated endocytosis and micropinocytosis. We observed that the entered BRSV initially localizes in early endosomes and subsequently localizes in late endosomes. Additionally, our results of western blot, virus titer and virus copies demonstrate that BRSV entry through clathrin-mediated endocytosis is regulated by PI3K-Akt and Src-JNK signaling pathways. Overall, our study suggests that BRSV enters MDBK cells through clathrin-mediated endocytosis, entered BRSV is trafficked to late endosome via early endosome, BRSV entry through clathrin-mediated endocytosis is regulated by PI3K-Akt and Src-JNK signaling pathways.

Keywords: bovine respiratory syncytial virus; clathrin; dynamin; endocytosis; endosomes.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by National Key R&D Programe for the 14th Five Year Plan (2022YFD1800500).