The Virion Host Shutoff Protein (U L 41) of Herpes Simplex Virus 1 Is an Endoribonuclease with a Substrate Specificity Similar to That of RNase A

Abstract

ABSTRACT Earlier, our laboratory reported that purified glutathione S -transferase-virion host shutoff (GST- vhs ) protein exhibited endoribonucleolytic activity in in vitro assays using as substrates in vitro-transcribed regions of IEX-1 mRNA. Here, we report that studies of the cleavage patterns of synthetic RNA oligonucleotides defined the activity of GST- vhs as being similar to that of RNase A. Thus, GST- vhs cleaved the RNA at the 3′ end of single-stranded cytidine and uridine residues. Since the GST-m vhs nuclease-defective mutant protein failed to cleave the synthetic RNAs, the results unambiguously attribute the activity to vhs .