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Rhinovirus 2A is the key protease responsible for instigating the early block to gene expression in infected cells

Rhinovirus 2A is the key protease responsible for instigating the early block to gene expression in infected cells
Rhinovirus 2A is the key protease responsible for instigating the early block to gene expression in infected cells
Human rhinoviruses express 2 cysteine proteases, 2A and 3C, that are responsible for viral polyprotein processing. Both proteases also suppress host gene expression by inhibiting mRNA transcription, nuclear export and cap-dependent translation. However, the relative contribution that each makes in achieving this goal remains unclear. In this study we have compared both the combined and individual ability of the 2 proteases to shut down in cellulo gene expression using a novel dynamic reporter system. Our findings show that 2A inhibits host gene expression much more rapidly than 3C. By comparing the activities of a representative set of proteases from the three different Human Rhinovirus (HRV) species, we also find variation in the speed at which host gene expression is suppressed. Our work highlights the key role that 2A plays in early suppression of the infected host cell response and shows that this can be influenced by natural variation in the activity of this enzyme.
rhinovirus, protease, 2A, 3C, ribozyme, mRNA destabilizing element, Nanoluciferase
0021-9533
Smart, David
3468eafa-5280-40a1-9fda-1bdc07dd914f
Filippi, Irene
46f16884-ad61-4502-a706-7565e07da0b2
Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b
Smalley, Benjamin
fedb3457-4f7f-406c-ad44-b4a39aa1f52e
Davies, Donna
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Mccormick, Christopher
0fce14bf-2f67-4d08-991f-114dd1e7f0bd
Smart, David
3468eafa-5280-40a1-9fda-1bdc07dd914f
Filippi, Irene
46f16884-ad61-4502-a706-7565e07da0b2
Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b
Smalley, Benjamin
fedb3457-4f7f-406c-ad44-b4a39aa1f52e
Davies, Donna
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Mccormick, Christopher
0fce14bf-2f67-4d08-991f-114dd1e7f0bd

Smart, David, Filippi, Irene, Blume, Cornelia, Smalley, Benjamin, Davies, Donna and Mccormick, Christopher (2020) Rhinovirus 2A is the key protease responsible for instigating the early block to gene expression in infected cells. Journal of Cell Science, 133 (1), [jcs232504]. (doi:10.1242/jcs.232504).

Record type: Article

Abstract

Human rhinoviruses express 2 cysteine proteases, 2A and 3C, that are responsible for viral polyprotein processing. Both proteases also suppress host gene expression by inhibiting mRNA transcription, nuclear export and cap-dependent translation. However, the relative contribution that each makes in achieving this goal remains unclear. In this study we have compared both the combined and individual ability of the 2 proteases to shut down in cellulo gene expression using a novel dynamic reporter system. Our findings show that 2A inhibits host gene expression much more rapidly than 3C. By comparing the activities of a representative set of proteases from the three different Human Rhinovirus (HRV) species, we also find variation in the speed at which host gene expression is suppressed. Our work highlights the key role that 2A plays in early suppression of the infected host cell response and shows that this can be influenced by natural variation in the activity of this enzyme.

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Accepted/In Press date: 2 December 2019
e-pub ahead of print date: 7 January 2020
Published date: 7 January 2020
Additional Information: This publication needs to be made REF returnable.
Keywords: rhinovirus, protease, 2A, 3C, ribozyme, mRNA destabilizing element, Nanoluciferase

Identifiers

Local EPrints ID: 436420
URI: http://eprints.soton.ac.uk/id/eprint/436420
ISSN: 0021-9533
PURE UUID: e7778b90-62ab-4e85-841a-652634ecfd70
ORCID for Cornelia Blume: ORCID iD orcid.org/0000-0001-6133-7318
ORCID for Donna Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Christopher Mccormick: ORCID iD orcid.org/0000-0002-6155-9161

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Date deposited: 10 Dec 2019 17:30
Last modified: 02 Dec 2020 05:01

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Contributors

Author: David Smart
Author: Irene Filippi
Author: Cornelia Blume ORCID iD
Author: Benjamin Smalley
Author: Donna Davies ORCID iD

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