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Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
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Differential Disruption of Nucleocytoplasmic Trafficking Pathways by Rhinovirus 2A Proteases
Kelly Watters1, Bahar Inankur2, Jaye C Gardiner1,3
1Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Journal of Virology
|February 10, 2017
Summary
Rhinovirus 2A proteases (2Apro) exhibit diverse activities, differentially targeting nuclear pore complex pathways. This protease variation explains strain-dependent host responses and distinct rhinovirus disease phenotypes.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Human rhinoviruses (RV) utilize 2A proteases (2Apro) for polyprotein processing and host cell shutoff.
- 2Apro cleaves nucleoporin proteins (Nups) within nuclear pore complexes (NPCs), impacting cellular transport.
- Diverse RV genotypes encode distinct 2Apro sequences with varying substrate specificities.
Purpose of the Study:
- To investigate the differential targeting of nuclear pore complex (NPC) pathways by various RV 2Apro.
- To correlate 2Apro activity with RV genotype-specific host cell responses and disease phenotypes.
Main Methods:
- Transformed HeLa cells expressing fluorescent cargos for importin and export pathways were used.
- Live-cell imaging assessed the disruption of NPC pathways by recombinant RV 2Apro (A16, A45, B04, B14, B52, C02, C15).
- NF-κB translocation and cytopathic effects were measured during infection with RVs and chimeras.
Main Results:
- Different RV 2Apro showed varying efficiencies and rates in disrupting import and export pathways.
- B04 and B52 proteases preferentially targeted import pathways; B04 and C15 targeted export pathways.
- Virus-type-specific trends in host response and cytopathic effects were observed.
Conclusions:
- Differential 2Apro activities contribute to strain-dependent host responses in RV infections.
- The study provides tools for real-time evaluation of host cell responses to RV.
- Understanding 2Apro diversity offers mechanistic insights into RV-induced disease phenotypes.
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