A Comparison of the Inhibition of Nucleocytoplasmic Trafficking by Viral Effectors from Cardioviruses and Rhinoviruses

Abstract

Cardioviruses and Enteroviruses of the Picornaviridae family exhibit similar infections. Viruses from the two genera inhibit nuclear import/export through the nuclear pore complex (NPC), a channel between the cytoplasm and nucleus. However, the diseases caused by viruses within these two genera vary in severity. Encephalomyocarditis virus (EMCV), a cardiovirus, uses a small potent protein called Leader (L) to inhibit trafficking through the NPC, thereby causing encephalitis in pigs and other animals. Human rhinovirus (HRV), an enterovirus, uses a protease, 2A, to inhibit trafficking through the nuclear pore and infection is associated with the common cold. It is unknown why cardioviruses and enteroviruses cause diseases of varying severity. In addition, little information is known about whether the mechanism of these viruses’ toxic proteins in inhibiting nuclear transport through the NPC, may correlate with the severity variation of the disease phenotypes of these viruses. To test this, we would compare the rates of nuclear efflux by three different Cardioviruses and three serotypes of HRV. Molecular techniques would be used to clone and express recombinant L proteins of the cardioviruses. Both nuclear efflux and nuclear import assays would be performed using recombinant green fluorescent protein (GFP) to track infection in HeLa cells for the effects of either L protein or 2A protease. This is done to determine the extent of inhibition of nuclear trafficking at the NPC. Knowledge of the kinetics between cardioviruses and HRV could hint at the different pathogenicities of these viruses. Also, it could add to our understanding of whether the genotype of a virus can infer the phenotype of the disease it causes.