Differential Disruption of Nucleocytoplasmic Trafficking Pathways by Rhinovirus 2A Proteases

摘要: The RNA rhinoviruses (RV) encode 2A proteases (2Apro) that contribute essential polyprotein processing and host cell shutoff functions during infection, including the cleavage of Phe/Gly-containing nucleoporin proteins (Nups) within nuclear pore complexes (NPC). Within 3 RV species, multiple divergent genotypes diverse 2Apro sequences act differentially on specific Nups. Since only subsets Phe/Gly motifs, particularly those Nup62, Nup98, Nup153, are recognized by transport receptors (karyopherins) when trafficking large molecular cargos through NPC, preferences individual predict genotype-specific targeting NPC pathways cargos. To test this idea, transformed HeLa lines were created with fluorescent (mCherry) for importin α/β, transportin 1, import Crm1-mediated export pathway. Live-cell imaging single cells expressing recombinant (A16, A45, B04, B14, B52, C02, C15) showed disruption each pathway measurably different efficiencies reaction rates. B04 B52 preferentially targeted Nups in pathways, while C15 more effective against Virus-type-specific trends also observed infection A16, viruses or their chimeras, as measured NF-κB (p65/Rel) translocation into nucleus rates virus-associated cytopathic effects. This study provides new tools evaluating response to infections real time suggests differential activities explain, part, strain-dependent responses disease phenotypes. IMPORTANCE Genetic variation among human rhinovirus types includes unexpected diversity genes encoding viral help these achieve antihost responses. When enzyme 7 comparatively programed reporter systems quantitative imaging, cellular substrates, complex, used indeed attacked at affinities. importance finding is it a mechanistic explanation how (strains) may elicit directly indirectly lead distinct phenotypes.