RT Journal Article
SR Electronic
T1 Rhinovirus 2A is the predominant protease responsible for instigating the early block to gene expression encountered in infected cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 591032
DO 10.1101/591032
A1 David Smart
A1 Irene Filippi
A1 Benjamin Smalley
A1 Donna Davies
A1 Christopher J. McCormick
YR 2019
UL http://biorxiv.org/content/early/2019/03/28/591032.abstract
AB 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.ActDactinomycin DAUF1AU-rich element RNA-binding protein 1CHXcycloheximideDAPI4,6-diamidino-2-phenylindoleEMCVencephalomyocarditis virusHCVhepatitis C virusGAPDHglyceraldehyde 3-phosphate dehydrogenaseHAhemagglutininHdVhepatitis delta virusHRVhuman rhinovirusIRESinternal ribosome entry siteNlucnanoluciferaseNLSnuclear localization signalNupnucleoporinRLUrelative light unitsVSVvesicular stomatitis virus