Influence of the Leader protein coding region of foot-and-mouth disease virus on virus replication

Graham Belsham

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    The foot-and-mouth disease virus (FMDV) Leader (L) protein is produced in two forms, Lab and Lb, differing only at their amino-termini, due to the use of separate initiation codons, usually 84 nt apart. It has been shown previously, and confirmed here, that precise deletion of the Lab coding sequence is lethal for the virus, whereas loss of the Lb coding sequence results in a virus that is viable in BHK cells. In addition, it is now shown that deletion of the ‘spacer’ region between these two initiation codons can be tolerated. Growth of the virus precisely lacking just the Lb coding sequence resulted in a previously undetected accumulation of frameshift mutations within the ‘spacer’ region. These mutations block the inappropriate fusion of amino acid sequences to the amino-terminus of the capsid protein precursor. Modification, by site-directed mutagenesis, of the Lab initiation codon, in the context of the virus lacking the Lb coding region, was also tolerated by the virus within BHK cells. However, precise loss of the Lb coding sequence alone blocked FMDV replication in primary bovine thyroid cells. Thus, the requirement for the Leader protein coding sequences is highly dependent on the nature and extent of the residual Leader protein sequences and on the host cell system used. FMDVs precisely lacking Lb and with the Lab initiation codon modified may represent safer seed viruses for vaccine production.
    Original languageEnglish
    JournalJournal of General Virology
    Volume94
    Issue numberPt 7
    Pages (from-to)1486-1495
    ISSN0022-1317
    DOIs
    Publication statusPublished - 2013

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