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J Gen Virol 89 (2008), 1036-1042; DOI 10.1099/vir.0.83428-0

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Short Communication

Occurrence, function and evolutionary origins of ‘2A-like’ sequences in virus genomes

Garry A. Luke1, Pablo de Felipe1, Alexander Lukashev2, Susanna E. Kallioinen1, Elizabeth A. Bruno1 and Martin D. Ryan1

1 Centre for Biomolecular Sciences, School of Biology, Biomolecular Sciences Building, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK
2 Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow 142782, Russia

Correspondence
Martin D. Ryan
martin.ryan{at}st-and.ac.uk

2A is an oligopeptide sequence mediating a ribosome ‘skipping’ effect, producing an apparent ‘cleavage’ of polyproteins. First identified and characterized in picornaviruses, ‘2A-like’ sequences are found in other mammalian viruses and a wide range of insect viruses. Databases were analysed using a motif conserved amongst 2A/2A-like sequences. The newly identified 2A-like sequences (30 aa) were inserted into a reporter polyprotein to determine their cleavage activity. Our analyses showed that these sequences fall into two categories. The majority mediated very high (complete) cleavage to separate proteins and a few sequences mediated cleavage with lower efficiency, generating appreciable levels of the uncleaved form. Phylogenetic analyses of 2A-like sequences and RNA-dependent RNA polymerases (RdRps) indicated multiple, independent, acquisitions of these sequences at different stages during virus evolution. Within a virus family, 2A sequences are (probably) homologous, but diverge due to other evolutionary pressures. Amongst different families, however, 2A/2A-like sequences appear to be homoplasic.

Supplementary material is available with the online version of this paper.






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