The Occurrence, Function, and Evolutionary Origins of ‘2A-like’ Sequences in Virus Genomes

Garry Alec Luke, Pablo De Felipe, Alexander Lukashev, Susanna Eveliina Kallioinen, Elizabeth A. Bruno, Martin Denis Ryan

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1036-1042
Number of pages7
JournalJournal of General Virology
Volume89
Issue number4
DOIs
Publication statusPublished - Apr 2008

Keywords

  • PICORNA-LIKE-VIRUS
  • DUCK HEPATITIS-VIRUS
  • MOUTH-DISEASE VIRUS
  • INFECTIOUS MYONECROSIS VIRUS
  • COMPLETE NUCLEOTIDE-SEQUENCE
  • DEPENDENT RNA-POLYMERASES
  • BEE PARALYSIS VIRUS
  • DOUBLE-STRANDED-RNA
  • CLEAVAGE ACTIVITIES
  • MOLECULAR ANALYSIS

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