Microfilaments and Microtubules Alternately Coordinate the Multistep Endosomal Trafficking of Classical Swine Fever Virus
Yan Cheng, Jin-xiu Lou, Chunchun Liu, Yayun Liu, Xiongnan Chen, Xiaodong Liang, Jin Zhang, Qian Yang, Yun Young Go, Bin Zhou
Abstract
Endocytosis, an essential biological process mediating cellular internalization events, is often exploited by pathogens for their entry into target cells. Previously, we have reported different mechanisms of CSFV endocytosis into the porcine epithelial cells (PK-15) and macrophages (3D4/21); however, the details of microfilaments/microtubules mediated virus migration within the host cells remained to be elucidated. In this study, we found that CSFV infection induced rearrangement of actin filaments regulated by cofilin through EGFR-PI3K/MAPK-RhoA/Rac1/Cdc42 pathway. Furthermore, we found that CSFV particles were trafficked along actin filaments in early and late endosomes, and through microtubules in lysosomes after entry. Here, we provide for the first time a comprehensive description of the cytoskeleton that facilitates entry and intracellular transport of highly pathogenic swine virus. Results from this study will greatly contribute to the understanding of virus-induced early and complex changes in host cells that are important in CSFV pathogenesis.