Foot-and-mouth disease virus L peptidase

Authors: Grubman, Marvin; De Los Santos, Teresa

Submitted to: Handbook of Proteolytic Enzymes
Publication Type: Book / Chapter
Publication Acceptance Date: 1/23/2013
Publication Date: 6/13/2013
Citation: Grubman, M.J., De Los Santos, T.B. 2013. Foot-and-mouth disease virus L peptidase. In: Neil D. Rawlings and Guy S. Salvesen, editors. Handbook of Proteolytic Enzymes. 3rd Edition. Oxford,UK:Academic Press. p.2183-2186.

Interpretive Summary:

Technical Abstract: Foot-and-mouth disease virus (FMDV), equine rhinitis A virus (ERAV) and bovine rhinitis B virus (BRBV) comprise the genus Aphthovirus of the Picornaviridae family. Seven genera within this family, Aphthoviruses, Cardioviruses, Erboviruses (ERBV), Kobuviruses, Senecaviruses, Sapeloviruses, and Teschoviruses encode a leader (L) protein. The FMDV L-protein was originally identified as a papain-like proteinase by sequence homology and demonstration of catalytic activity. ERAV, BRBV, and ERBV L-proteins also have proteinase activity, whereas L proteins from the other Picornaviridae genera are proteolytically inactive. For FMDV there are two in-frame AUG codons at the beginning of the viral genome open reading frame, resulting in the synthesis of two L-proteins, Lab and Lb. Lb, the smaller of the two proteins, is the major synthesized species, and its sequence is highly conserved among the FMDV subtypes and serotypes. The ERAV and BRBV genomes also possess in-frame start sites in a similar position to the FMDV AUG codons. In contrast to FMDV, for ERAV the larger of the two L proteins, Lab, is the predominant species, while for BRBV, like for FMDV, the smaller Lb is the major protein found in infected cells. The active site residues of FMDV L proteinase have been identified and its crystal structure and solution structure have been determined at high resolution. A number of studies have contributed to the understanding of the role of L in virus replication. A genetic variant of FMDV, lacking the L protein coding region, was constructed and was significantly attenuated in naturally susceptible animals suggesting that while L is not required for growth in tissue culture it has a role in interacting with the host. The FMDV L protein has a number of functions related to blocking the host innate immune response including, 1) cleavage of the translation initiation factor eIF4G, 2) involvement in the cleavage of the transcription factor NF-kappaB, 3) degradation of the transcription factors interferon regulatory factors 3 and 7, and 4) ubiquitin (Ub)-protease activity responsible for removal of Ub moieties from cellular targets. In summary the FMDV L protein is a virulence factor, or as recently defined a security protein, that has evolved multiple mechanisms to block the host response to viral infection.