Plum Island Animal Disease Center
'The Role of the Leader Protein of Foot-and-Mouth Disease Virus as a Virulence Factor'
Unfortunately, Dr Marvin Grubman was not able to attend the meeting but Dr Louis Rodriquez, his colleague, gave the keynote presentation instead. He described the work done with the leader protein (Lpro) of foot-and-mouth disease virus (FMDV) by Dr Grubman and his co-workers at the Plum Island Animal Disease Center, USA. The presentation consisted of three parts: (i) the development of leaderless FMDV; (ii) the inhibition of host innate response by FMDV-Lpro; and (iii) the identification of protein domains in Lpro and the mechanism of action.
The genome of FMDV is a positive-sense, single-strand RNA molecule and is translated into a polyprotein which is processed by the viral encoded proteinases, L, 2A and 3C into structural and non-structural proteins. Lpro, the first translation product, cleaves itself from the polypeptide chain and also cleaves the translation initiation factor eIF-4G which is required for translation of capped mRNAs. Translation of FMDV mRNA is cap-independent and so cleavage of eIF-4G by L results in the shut-down of host cell protein synthesis.
Dr Grubman and his co-workers, by constructing a genetic variant of FMDV lacking the complete L coding region, demonstrated that the leaderless virus was highly attenuated for cattle and pigs. In elegant experiments they investigated the mechanism of action of Lpro at the molecular level and concluded that it functions as a virulence factor by disrupting the host cell at both the transcriptional and translational levels.
These studies offer the exciting possibility of a new strategy for genetically engineering FMD vaccines.