Expression of exogenous IFN-alpha by bypassing the translation block protects cells against FMDV infection.
Foot-and-mouth disease virus (FMDV) is the most contagious pathogen of cloven-hoofed animals. Previous studies have demonstrated that type I interferons [alpha/beta interferons (IFN-alpha/betas)] can suppress FMDV replication and spread. Conversely, FMDV can also inhibit IFN-alpha expression in infected cells by blocking cap-dependent translation. To overcome the blockade on IFN-alpha mRNA translation during FMDV infection, we generated an IRES-IFN construct that carries FMDV's internal ribosome entry site (IRES) cDNA sequence between the promoter and porcine IFN-alpha gene. ELISA assays indicated that expression of IFN-alpha regulated by wild-type IRES increased to 125% of pre-infection level after infection for 24h, but the expression of IFN-alpha regulated by nonfunctional IRES mutants were only approximately 50% of pre-infection level. Correspondingly, the former could suppress the replication of FMDV to 20% of the latter and protect cells against FMDV for a longer time. Therefore, these findings provide a new strategy to anti-FMDV therapy.
Xiong
Yi
Y
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
Lin
Meijuan
M
Yuan
Bing
B
Yuan
Tingting
T
Zheng
Congyi
C
D000818:Animals; D002460:Cell Line; D005536:Foot-and-Mouth Disease / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000502:physiology*; D015870:Gene Expression; D016898:Interferon-alpha / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism; D013552:Swine; D013553:Swine Diseases / Q000235:genetics* / Q000378:metabolism / Q000821:virology
D016898:Interferon-alpha; D012315:RNA Caps