Exploitation of nuclear functions by human rhinovirus, a cytoplasmic RNA virus

PLoS Pathogens
Dylan FlatherPaul D Gershon

Abstract

Protein production, genomic RNA replication, and virion assembly during infection by picornaviruses like human rhinovirus and poliovirus take place in the cytoplasm of infected human cells, making them the quintessential cytoplasmic pathogens. However, a growing body of evidence suggests that picornavirus replication is promoted by a number of host proteins localized normally within the host cell nucleus. To systematically identify such nuclear proteins, we focused on those that appear to re-equilibrate from the nucleus to the cytoplasm during infection of HeLa cells with human rhinovirus via quantitative protein mass spectrometry. Our analysis revealed a highly selective re-equilibration of proteins with known mRNA splicing and transport-related functions over nuclear proteins of all other functional classes. The multifunctional splicing factor proline and glutamine rich (SFPQ) was identified as one such protein. We found that SFPQ is targeted for proteolysis within the nucleus by viral proteinase 3CD/3C, and a fragment of SFPQ was shown to migrate to the cytoplasm at mid-to-late times of infection. Cells knocked down for SFPQ expression showed significantly reduced rhinovirus titers, viral protein production, and viral RNA ac...Continue Reading

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Jun 12, 2019·Cells·Tanner M TessierJoe S Mymryk
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Mar 12, 2021·Journal of Cell Science·Jiamin YiHaixue Zheng

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Methods Mentioned

BETA
confocal microscopy
transfection
PCR
electrophoresis
crosslinking studies
protein
pulldown

Software Mentioned

Clarity chromatography
Quantity One
Mascot Distiller
NetPicoRNA
Zen

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