Bifidobacterium as an oral delivery carrier of interferon-alpha2b for the treatment of coxsackievirus B3-induced myocarditis in the BALB/c mice

Abstract

Objective To investigate a novel oral delivery system for interferon-alpha2b using genetically engineered Bifidobacterium longum as the carrier and further evaluate the efficacy of interferon (IFN)-α2b-expressed B.longum on the coxsackie B3 virus (CVB3)-induced myocarditis in mice.Methods IFN-α2b recombinant B.longum was amplified in vivo and subsequently,BLAB/c mice were inoculated intraperitoneally with infectious dose of CVB3 for two weeks to produce the models of CVB3-induced myocarditis.Then,the murine models were divided into four groups.The BIFN group was orally administered with IFN-α2b-transformed B.longum for two weeks respectively after the inoculation of the virus.Plasmid control group was orally administered with plasmid control-transformed B.longum. Saline group was administered intraperitoneally with sterile phosphate buffer (PBS).IFN group was intramuscullarly injected with IFN-α2b.All animals were killed on the day 14 post-treatment,and the murine hearts were dissected aseptically for hematoxylin-eosin (HE) staining,viral titration and RNA extraction for interferon-induced Mx1 gene transcriptional quantification.Results The data indicated that oral administration of IFN-α2b-expressed B.longum for two weeks after CVB3 infection in the BLAB/c mice could alleviate the severity of virus-induced myocarditis (0.16 ± 0.10,P ＜ 0.01),markedly reduce the virus titers in the heart (3.03 ±0.02),and induce IFN-γ,tumor necrosis factor (TNF)-α and Mx1 gene transcription (1.48 ± 0.08,3.56 ± 0.02,2.13 ± 0.01,respectively) in the heart compared with the controls (P ＜ 0.01).Conclusion Oral administration of IFN-α2b recombinant B.longum may play a therapeutic role in the treatment of CVB3-induced myocarditis in the mice. Key words: Bifidobacterium; Interferon-alpha2b; Coxsackie virus B3 ; Myocarditis ; Enterovirus