Related Experiment Video
Updated: Sep 20, 2025
Generation of Recombinant Influenza Virus from Plasmid DNA
Published on: August 3, 2010
Epidermal growth factor receptor (EGFR) promotes uptake of bovine parainfluenza virus type 3 into MDBK cells
Wei Pan1, Yaodong Xia1, Hongmei Wang1
1Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan 250014, China; Key Laboratory of Animal Resistant Biology of Shandong, College of Life Sciences, Shandong Normal University, Jinan 250014, China.
Abstract:
Bovine parainfluenza virus 3 (BPIV3) is an important respiratory pathogen of both young and adult cattle. The pathways of cell entry are highly related to viral transmission and pathogenicity. In previous studies, we demonstrated that macropinocytosis and clathrin-dependent endocytosis play critical roles in the entry of BPIV3 into MDBK cells. Macropinocytosis is special endocytic process which need to activate signaling pathways that remodle the actin cytoskeleton. Parainfluenza viruses (PIVs) initiate infection by binding to sialic acid receptors on cell surfaces. Nevertheless, sialic acids are not able to transmit signals across the plasma membrane, indicating the necessity for additional signaling receptors. Here, we have demonstrated that specific inhibitors and siRNAs targeting EGFR inhibit the entry of BPIV3 into MDBK cells. BPIV3 productive infection in MDBK cells led to activation of EGFR. Inactivation of EGFR suppressed BPIV3-induced rearrangement of the F-actin cytoskeleton. In addition, PI3K-Akt and ERK1/2 were activated in an EGFR-dependent manner during BPIV3 infection. Specific inhibitors targeting these canonical downstream effectors of EGFR could significantly reduce viral entry efficacy. Moreover, we also demonstrated that the important regulators of macropinocytosis, Rac1 and Pak1, are downstream mediators of EGFR during BPIV3 internalization. These results indicated that EGFR is a host-entry cofactor used by BPIV3 to enter MDBK cells.
Insights
Bovine parainfluenza virus 3 (BPIV3) uses the Epidermal Growth Factor Receptor (EGFR) to enter cattle cells. EGFR activation is crucial for viral entry and cytoskeleton changes, impacting BPIV3 infection.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Bovine parainfluenza virus 3 (BPIV3) causes significant respiratory illness in cattle.
- Viral entry mechanisms are key to understanding BPIV3 transmission and disease.
- Previous work identified macropinocytosis and clathrin-dependent endocytosis in BPIV3 entry.
Purpose of the Study:
- To investigate the role of Epidermal Growth Factor Receptor (EGFR) in BPIV3 cell entry.
- To elucidate the signaling pathways downstream of EGFR involved in BPIV3 infection.
Main Methods:
- Utilized specific EGFR inhibitors and siRNAs to block BPIV3 entry into MDBK cells.
- Assessed EGFR activation and F-actin cytoskeleton rearrangement during BPIV3 infection.
- Analyzed the activation of downstream signaling pathways (PI3K-Akt, ERK1/2) and macropinocytosis regulators (Rac1, Pak1).
Main Results:
- EGFR inhibition significantly reduced BPIV3 entry into MDBK cells.
- BPIV3 infection activated EGFR, which was essential for F-actin cytoskeleton remodeling.
- EGFR-dependent activation of PI3K-Akt and ERK1/2 pathways, as well as Rac1 and Pak1, was observed.
- Inhibiting these downstream pathways also reduced viral entry efficacy.
Conclusions:
- EGFR acts as a host-entry cofactor for BPIV3 in MDBK cells.
- EGFR signaling is critical for BPIV3-mediated cytoskeletal changes and viral internalization.
- Targeting EGFR and its downstream pathways presents a potential strategy for controlling BPIV3 infections.
