id author title date pages extension mime words sentences flesch summary cache txt cord-355671-t890eixt Medina, Gisselle N. Impairment of the DeISGylation Activity of Foot-and-Mouth Disease Virus Lpro Causes Attenuation In Vitro and In Vivo 2020-06-16 .txt text/plain 6363 346 46 FMDV Lpro is a papain-like protease (PLP) known to block the cellular innate immune response, at both the transcriptional and translational level by utilizing different mechanisms, including (i) shutting down translation of host capped mRNAs through the cleavage of the translation initiation factor eIF4G (5, 6); (ii) downregulating IFN mRNA expression by causing degradation of NF-B, IRF-3, IRF-7, and LGP2 (7-10); (iii) targeting the chromatin remodeling machinery to disrupt the expression of IFN and ISG mRNAs (11) ; and (iv) targeting of G3BP1/2 to block stress granule formation (12) . Importantly, engineering of an infectious clone carrying this mutation (LproW105A) rendered a viable FMDV with a perceptible level of attenuation and reduced deISGylation and DUB activity compared with wild-type (WT) virus during infection of porcine cells. To confirm these results using the FMDV host-specific ISGylation machinery during infection, we cloned the porcine ISG15 in a replicationdefective human adenovirus type 5 (Ad5) vector (Fig. 5B) and examined its antiviral activity in swine cells. ./cache/cord-355671-t890eixt.txt ./txt/cord-355671-t890eixt.txt