Yang, Decheng (The University of British Columbia)

Purpose

Picornaviral infection causes global shutdown of host gene translation but still maintains essential translation of certain host genes supporting viral replication. In the search for such host cellular mRNAs, the 5’TOP (terminal oligopyrimidine tract) mRNAs are candidates of interest. The 5’TOP motif is defined by a 7-methyl-G cap followed by a C and then a stretch of 4-15 CU at the 5’ end of mRNA. The 5’TOP mRNAs (~30% of total cellular mRNAs) encode proteins of translational machinery such as ribosomal proteins and translation initiation and elongation factors. The presence of the 5’TOP motif within these mRNAs has previously been shown to cause its translation repression in conditions of cellular stress, such as starvation, radiation, and heat shock. Surprisingly, we recently found that cellular stress caused by infection of coxsackievirus B3 (CVB3), a member of picornavirus family, induced significantly enhanced expression of eukaryotic translation elongation factor 1A (eEF1A), a 5’TOP mRNA, at both the RNA and protein levels. We also found that this upregulation is parallel with increased viral protein synthesis. However, the underlying mechanism is unknown.