scholarly journals Bovine Plasmacytoid Dendritic Cells Are the Major Source of Type I Interferon in Response to Foot-and-Mouth Disease Virus In Vitro and In Vivo

2011 ◽  
Vol 85 (9) ◽  
pp. 4297-4308 ◽  
Author(s):  
E. Reid ◽  
N. Juleff ◽  
S. Gubbins ◽  
H. Prentice ◽  
J. Seago ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Disease Virus ◽  
Type I Interferon ◽  
Foot And Mouth Disease ◽  
Plasmacytoid Dendritic Cells ◽  
Mouth Disease ◽  
Type I ◽  
Mouth Disease Virus

scholarly journals Impairment of the DeISGylation Activity of Foot-and-Mouth Disease Virus Lpro Causes Attenuation In Vitro and In Vivo

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Gisselle N. Medina ◽  
Paul Azzinaro ◽  
Elizabeth Ramirez-Medina ◽  
Joseph Gutkoska ◽  
Ying Fang ◽  
...  
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Type I ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Infected Cells ◽  
Viral Attenuation

ABSTRACT Foot-and-mouth disease virus (FMDV) leader proteinase (Lpro) affects several pathways of the host innate immune response. Previous studies in bovine cells demonstrated that deletions (leaderless [LLV]) or point mutations in Lpro result in increased expression of interferon (IFN) and IFN-stimulated genes (ISGs), including, among others, the ubiquitin-like protein modifier ISG15 and the ubiquitin specific peptidase USP18. In addition to its conventional papain-like protease activity, Lpro acts as a deubiquitinase (DUB) and deISGylase. In this study, we identified a conserved residue in Lpro that is involved in its interaction with ISG15. Mutation W105A rendered Escherichia coli-expressed Lpro unable to cleave the synthetic substrate pro-ISG15 while preserving cellular eIF4G cleavage. Interestingly, mutant FMDV W105A was viable. Overexpression of ISG15 and the ISGylation machinery in porcine cells resulted in moderate inhibition of FMDV replication, along with a decrease of the overall state of ISGylation in wild-type (WT)-infected cells. In contrast, reduced deISGylation was observed upon infection with W105A and leaderless virus. Reduction in the levels of deubiquitination was also observed in cells infected with the FMDV LproW105A mutant. Surprisingly, similarly to WT, infection with W105A inhibited IFN/ISG expression despite displaying an attenuated phenotype in vivo in mice. Altogether, our studies indicate that abolishing/reducing the deISGylase/DUB activity of Lpro causes viral attenuation independently of its ability to block the expression of IFN and ISG mRNA. Furthermore, our studies highlight the potential of ISG15 to be developed as a novel biotherapeutic molecule against FMD. IMPORTANCE In this study, we identified an aromatic hydrophobic residue in foot-and-mouth disease virus (FMDV) leader proteinase (Lpro) (W105) that is involved in the interaction with ISG15. Mutation in Lpro W105 (A12-LproW105A) resulted in reduced deISGylation in vitro and in porcine-infected cells. Impaired deISGylase activity correlated with viral attenuation in vitro and in vivo and did not affect the ability of Lpro to block expression of type I interferon (IFN) and other IFN-stimulated genes. Moreover, overexpression of ISG15 resulted in the reduction of FMDV viral titers. Thus, our study highlights the potential use of Lpro mutants with modified deISGylase activity for development of live attenuated vaccine candidates, and ISG15 as a novel biotherapeutic against FMD.

scholarly journals A novel type I interferon, interferon alphaomega, shows antiviral activity against foot-and-mouth disease virus in vitro

2019 ◽  
Vol 127 ◽  
pp. 79-84 ◽  
Author(s):  
Shi-fang Li ◽  
Mei-jiao Gong ◽  
Yin-li Xie ◽  
Jun–jun Shao ◽  
Fu-rong Zhao ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Disease Virus ◽  
Type I Interferon ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Type I ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Porcine Type I Interferon Rapidly Protects Swine Against Challenge with Multiple Serotypes of Foot-and-Mouth Disease Virus

2011 ◽  
Vol 31 (2) ◽  
pp. 227-236 ◽  
Author(s):  
Camila C.A. Dias ◽  
Mauro P. Moraes ◽  
Fayna Diaz-San Segundo ◽  
Teresa de los Santos ◽  
Marvin J. Grubman
Keyword(s):  
Disease Virus ◽  
Type I Interferon ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Type I ◽  
Mouth Disease Virus ◽  
Foot And Mouth
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