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

Abstract

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 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β 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.