Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses

Foot-and-mouth disease virus (FMDV) leader protein (L-pro) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L-pro exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L-pro self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L-pro also has the ability to antagonize host antiviral effects. To promote FMDV replication, L-pro can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 gamma (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-alpha/beta production; and (3) L-pro can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L-pro, this review introduces the basic properties of L-pro and the mechanisms by which it antagonizes host antiviral responses.