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Infectious pancreatic necrosis virus enters CHSE-214 cells via macropinocytosis
Jorge Levican1, Camila Miranda-Cárdenas1, Ricardo Soto-Rifo1
1Programa de Virología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Abstract:
Infectious pancreatic necrosis virus (IPNV) is a non-enveloped virus belonging to the Birnaviridae family. IPNV produces an acute disease in salmon fingerlings, with high mortality rates and persistent infection in survivors. Although there are reports of IPNV binding to various cells, the viral receptor and entry pathways remain unknown. The aim of this study was to determine the endocytic pathway that allows for IPNV entry. We observed that IPNV stimulated fluid uptake and virus particles co-localysed with the uptake marker dextran in intracellular compartments, suggesting a role for macropinocytosis in viral entry. Consistent with this idea, viral infection was significantly reduced when the Na+/H+ exchanger NHE1 was inhibited with 5-(N-Ethyl-N-isopropyl) amiloride (EIPA). Neither chlorpromazine nor filipin complex I affected IPNV infection. To examine the role of macropinocytosis regulators, additional inhibitors were tested. Inhibitors of the EGFR pathway and the effectors Pak1, Rac1 and PKC reduced viral infection. Together, our results indicate that IPNV is mainly internalized into CHSE-214 cells by macropinocytosis.
Insights
Infectious pancreatic necrosis virus (IPNV) enters salmon cells primarily through macropinocytosis. Inhibiting macropinocytosis regulators significantly reduced IPNV infection, confirming this entry pathway.
Area of Science:
- Virology
- Cell Biology
- Aquatic Animal Health
Background:
- Infectious pancreatic necrosis virus (IPNV) causes significant mortality and persistent infections in salmon.
- The viral receptor and entry mechanisms of IPNV remain largely uncharacterized.
- Understanding viral entry pathways is crucial for developing effective control strategies.
Purpose of the Study:
- To elucidate the endocytic pathway utilized by IPNV for cellular entry.
- To identify key cellular processes and regulators involved in IPNV internalization.
Main Methods:
- Investigated IPNV entry using fluid uptake assays and co-localization studies with dextran.
- Utilized specific inhibitors targeting different endocytic pathways, including macropinocytosis.
- Assessed the impact of inhibiting macropinocytosis regulators (NHE1, EGFR pathway, Pak1, Rac1, PKC) on viral infection.
Main Results:
- IPNV stimulated fluid uptake and co-localized with dextran, indicating macropinocytosis involvement.
- Inhibition of Na+/H+ exchanger NHE1 with EIPA significantly reduced IPNV infection.
- Inhibitors of EGFR pathway, Pak1, Rac1, and PKC also decreased viral entry.
- Chlorpromazine and filipin complex I did not affect IPNV infection, ruling out clathrin-mediated and caveolae-mediated pathways.
Conclusions:
- IPNV is primarily internalized into CHSE-214 cells via macropinocytosis.
- Macropinocytosis regulators play a critical role in IPNV cellular entry.
- Findings provide insights into the molecular mechanisms of IPNV infection and potential therapeutic targets.
