Author: Sun, Di; Chen, Shun; Cheng, Anchun; Wang, Mingshu
Title: Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells Document date: 2016_3_17
ID: 07nfb69o_50
Snippet: A novel model shows that CVB3 manipulates transactive response DNA-binding protein-43 (TDP-43) to regulate viral pathogenesis. Normally, TDP-43 regulates RNA metabolism in the nucleus as a heterogeneous ribonucleoprotein (hnRNP), and a pathophysiological link between TDP-43 and amyotrophic lateral sclerosis (ALS) has been established [122] . When cells are infected by CVB3, 2A pro induces translocation of TDP-43 from the nucleus to the cytoplasm......
Document: A novel model shows that CVB3 manipulates transactive response DNA-binding protein-43 (TDP-43) to regulate viral pathogenesis. Normally, TDP-43 regulates RNA metabolism in the nucleus as a heterogeneous ribonucleoprotein (hnRNP), and a pathophysiological link between TDP-43 and amyotrophic lateral sclerosis (ALS) has been established [122] . When cells are infected by CVB3, 2A pro induces translocation of TDP-43 from the nucleus to the cytoplasm. TDP-43 is then cleaved by 3C pro at Q327, generating two fragments. The C-terminal fragment of TDP-43 is rapidly degraded, whereas the N-terminal product negatively regulates the function of native TDP-43 [123] . These processes benefit viral replication. The cleavage of full-length TDP-43 is closely related to neurodegeneration. Studies of 3C pro and TDP-43 will provide information regarding the pathogenesis of CV. [113] The development of effective immune evasion mechanisms is beneficial to viral infection. Evidence has shown that picornaviruses adopt multiple mechanisms to suppress host antiviral responses. EV encodes 2A pro and 3C pro for polyprotein processing, whereas FMDV encodes L pro and 3C pro . These proteins with proteolytic activity target and cleave certain cellular proteins to down-regulate the type I IFN response, pro-inflammatory cytokines and ISG induction. HAV encodes 3C pro for its polyprotein processing. The multipronged cleavage of innate immune proteins is a remarkable example of picornaviral evolution through 3C pro and its 3ABC and 3CD precursors, and 3C pro can bind to and cleave different cellular molecules to interfere with antiviral signaling pathways to evade host immune response.
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