Host microRNA-203a Is antagonistic to the progression of foot-and-mouth disease virus infection.
Sam68 was previously shown to be a critical host factor for foot-and-mouth disease virus (FMDV) replication. MicroRNA (miR) miR-203a is reportedly a negative regulator of Sam68 expression both in vitro and in vivo. Here, transfection of miR-203a-3p and miR-203a-5p mimics separately and in combination in a porcine cell line followed by FMDV infection resulted in diminished viral protein synthesis and a 4 and 6log reduction in virus titers relative to negative controls, respectively. Unexpectedly, Sam68 expression was increased by miR-203a-5p transfection, but not miR-203a-3p. miR-203a-5p also down-regulated Survivin expression, which was predicted to play a role in FMDV infection. Moreover, miR-203a-5p but not miR-203a-3p affected a reduction in FMDV viral RNA. These effects were not replicated with a related Picornavirus, suggesting FMDV specificity. Importantly, miR-203a-3p and miR-203a-5p impaired FMDV infection across multiple FMDV serotypes. We concluded that miR-203a-3p and miR-203a-5p represent attractive potential naturally occurring bio-therapeutics against FMDV.
Plum Island Animal Disease Center Foreign Animal Disease Research Unit (FADRU) Agricultural Research Service (ARS), United States Department of Agriculture (USDA), 40550 Route 25, Orient Point, NY 11957, United States.
Joseph
J
Gutkoska
Plum Island Animal Disease Center Foreign Animal Disease Research Unit (FADRU) Agricultural Research Service (ARS), United States Department of Agriculture (USDA), 40550 Route 25, Orient Point, NY 11957, United States.
Michael
M
LaRocco
Plum Island Animal Disease Center Foreign Animal Disease Research Unit (FADRU) Agricultural Research Service (ARS), United States Department of Agriculture (USDA), 40550 Route 25, Orient Point, NY 11957, United States.
Elizabeth
E
Ramirez-Medina
Plum Island Animal Disease Center Foreign Animal Disease Research Unit (FADRU) Agricultural Research Service (ARS), United States Department of Agriculture (USDA), 40550 Route 25, Orient Point, NY 11957, United States.
Teresa
T
de Los Santos
Plum Island Animal Disease Center Foreign Animal Disease Research Unit (FADRU) Agricultural Research Service (ARS), United States Department of Agriculture (USDA), 40550 Route 25, Orient Point, NY 11957, United States. Electronic address: paul.lawrence@ars.usda.gov.
Paul
P
Lawrence
D000818:Animals; D002417:Cattle; D002460:Cell Line; D018450:Disease Progression; D004285:Dogs; D029650:Enterovirus, Bovine / Q000235:genetics; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000254:growth & development*; D061985:Madin Darby Canine Kidney Cells; D035683:MicroRNAs / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013552:Swine; D019562:Viral Load / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*
D035683:MicroRNAs; D034741:RNA, Small Interfering
Bio-therapeutic; Foot-and-mouth disease virus (FMDV); MiR); MiR-203a-3p; MiR-203a-5p; MicroRNA (miRNA; Sam68; Survivin