The potential role of Simian Virus 40 polyA sequence (SV40 polyA) to mediate stress-inducible mRNA translation

Abstract

Viral infection of a cell is often associated with the development of cellular stress. Although the inhibition of global mRNA translation is a common cellular response to stress, many viruses are still able to exploit the protein synthesis machinery of the host cells for production of viral proteins. In this study, we examined if certain sequence element in the SV40 viral genome may enable synthesis of viral proteins to take place despite the presence of cellular stress. The pEGFP-c1 expression plasmid that incorporates the SV40 polyA sequence in its transcript was used as a model system for this study. We found that the expression of pEGFP-c1 in several mammalian cell lines could be markedly enhanced by the presence of stress inducers such as arsenite, cadmium, and thapsigargin, all of which were shown to result in eIF2-alpha phosphorylation and inhibition of global protein synthesis. The co-treatment of cells with cycloheximide abolished the stress-induced increase in GFP expression. The deletion of the 5' 1–120 nucleotides of SV40 polyA markedly diminished stress-induced increase of GFP expression. However, the expression of GFP using the pcDNA3 plasmid that does not have the SV40 polyA in its transcript was not altered in the presence of stress inducers. These results suggest the interesting idea that SV40 polyA play a hitherto unrecognized role in viral gene expression.