title: Expression of porcine Mx1 with FMDV IRES enhances the antiviral activity against foot-and-mouth disease virus in PK-15 cells.
abstract: Foot-and-mouth disease virus (FMDV) is the most contagious pathogen in cloven-hoofed (two-toed) animals. Due to the rapid replication and spread of FMDV, novel therapeutic strategies are greatly needed to reduce or block FMDV shedding in cases of disease outbreak. Here, we generated an IRES-Mx1 construct in which the internal ribosome entry site (IRES) of FMDV was inserted between the promoter and open reading frame (ORF) of porcine myxovirus resistance protein 1 (poMx1). This construct provides more powerful protection against FMDV infection than the IRES-IFN construct that was previously generated by our group. The results indicate that this IRES-Mx1 construct was able to express poMx1 12 h after transfection and induce a robust immune response. In contrast to the control, the proliferation of virus in transfected cells was significantly inhibited, as evaluated by morphology monitoring, real-time RT-PCR, virus titration and Western blot. In addition, we also found that the antiviral activity in cells transfected with pc-IRES-Mx1 was abolished when the JAK/STAT pathway was repressed, which indicates that the antiviral mechanism of poMx1 is JAK/STAT pathway dependent. Taken together, our data suggest that the antiviral activity of poMx1 is possibly produced by affecting the host cells themselves, instead of interacting with the virus directly. The new construct reported here could be used as a novel effective therapy against FMDV infection.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yuan
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.forename: Chao
authors.initials: C
authors.lastname: Shen
authors.forename: Congyi
authors.initials: C
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002460:Cell Line; D005536:Foot-and-Mouth Disease / Q000235:genetics / Q000276:immunology* / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D064547:Myxovirus Resistance Proteins / Q000235:genetics* / Q000276:immunology*; D012045:Regulatory Sequences, Nucleic Acid; D013552:Swine; D014779:Virus Replication
chemical_list: D064547:Myxovirus Resistance Proteins