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 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.
State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China. 496104087@qq.com.|College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. 496104087@qq.com.
Yingqi
Y
Liu
State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China. zhuzixiang@126.com.
Zixiang
Z
Zhu
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. miaotaozhang@126.com.
Miaotao
M
Zhang
State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China. haixuezheng@163.com.
Haixue
H
Zheng
D000818:Animals; D001188:Artiodactyla; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005536:Foot-and-Mouth Disease / Q000276:immunology* / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D007113:Immunity, Innate
D010450:Endopeptidases; C088747:leader proteinase, foot-and-mouth disease virus