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Title: Theiler’s murine encephalomyelitis virus contrasts with encephalomyocarditis and foot-and-mouth disease viruses in its functional utilization of the StopGo non-standard translation mechanism

Author
item LOUGHRAN, G - University College Cork
item LIBBEY, J - University Of Utah
item UDDOWLA, SABENA - Oak Ridge Institute For Science And Education (ORISE)
item SCALLAN, M - University College Cork
item RYAN, M - University Of St Andrews
item FUJINAMI, R - University Of Utah
item Rieder, Aida - Elizabeth
item ATKINS, J - University Of Utah

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/20/2012
Publication Date: 2/1/2013
Citation: Loughran, G., Libbey, J.E., Uddowla, S., Scallan, M.F., Ryan, M.D., Fujinami, R.S., Rieder, A.E., Atkins, J.F. 2013. Theiler’s murine encephalomyelitis virus contrasts with encephalomyocarditis and foot-and-mouth disease viruses in its functional utilization of the StopGo non-standard translation mechanism. Journal of General Virology. 94(2):348-353.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) is a member of a group of viruses called “Picornaviruses”. These viruses replicate inside the cell through the expression of a single polyprotein that is cleaved by viral proteins called proteases. In FMDV, an early cleavage event releases the capsid proteins (those protecting the viral RNA) along with a short protein called 2A by process known as ‘StopGo’. Using genetic and biochemical analysis, we demonstrated the indispensability of the StopGo function for FMDV infectivity. That was not the case for Theiler’s murine encephalomyelitis virus, another picornavirus from mice. This research identified parts of the protein 2A involved in the StopGo process that could be suitable targets for antiviral interventions against FMDV.

Technical Abstract: The picornaviruses’ genome consists of a positive-sense single-stranded RNA. Like many picornaviruses, cardioviruses synthesize two distinct polyprotein precursors from adjacent but non-overlapping genome segments. Both the [L-1ABCD-2A] and the [2BC-3ABCD] polyproteins are proteolytically processed to yield mature capsid and non-structural proteins, respectively. An unusual translational event, known as ‘StopGo’ or ‘Stop-Carry on’, is responsible for release of the [L-1ABCD-2A] polyprotein from the ribosome and synthesis of the N-terminal amino acid of the [2BC-3ABCD] polyprotein. A common feature of these viruses is the presence of a highly conserved signature sequence for StopGo: -D(V/I)ExNPG'P-, where -D(V/I)ExNPG are the last seven amino acids of 2A, and the last P- is the first amino acid of 2B. Here we report that, in contrast to encephalomyocarditis virus and foot-and-mouth disease virus, a functional StopGo does not appear to be essential for Theiler’s murine encephalomyelitis virus viability when tested in vitro and in vivo.