Virus receptor trap neutralizes coxsackievirus in experimental murine viral myocarditis

• Published in: Cardiovascular research 2006-08, Vol.71 (3), p.517-526
• Main Authors: LIM, Byung-Kwan, CHOI, Jin-Ho, NAM, Jae-Hwan, GIL, Chae-Ok, SHIN, Jae-Ok, YUN, Soo-Hyeon, KIM, Duk-Kyung, JEON, Eun-Seok
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Biological and medical sciences; Capsid Proteins - metabolism; Cardiology. Vascular system; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Coxsackievirus Infections - metabolism; Coxsackievirus Infections - pathology; Coxsackievirus Infections - therapy; Disease Models, Animal; Electroporation - methods; Genetic Therapy - methods; Heart; HeLa Cells; Humans; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred BALB C; Myocarditis - metabolism; Myocarditis - pathology; Myocarditis - therapy; Myocarditis - virology; Myocarditis. Cardiomyopathies; Receptors, Virus - genetics; Receptors, Virus - metabolism; Recombinant Fusion Proteins - therapeutic use; Survival Analysis
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2006.05.016

The coxsackie and adenovirus receptor (CAR) and the decay-accelerating factor (DAF) are receptors for coxsackievirus B3 (CVB3), which is known as the major cause of human viral myocarditis. We investigated the potential for therapeutic use of soluble virus receptor fusion proteins. We designed and generated a novel virus receptor trap (hCAR-hDAF:Fc) consisting of both CVB3 receptors and the Fc portion of human IgG1 and evaluated its antiviral effects in experimental CVB3 myocarditis. Among four soluble virus receptor fusion proteins (hCAR:Fc, hDAF:Fc, hCAR-hDAF:Fc and hDAF-hCAR:Fc), hCAR:Fc and hCAR-hDAF:Fc in the supernatant of transfected cells neutralized echovirus, adenovirus, and various serotypes of CVB in a dose-dependent manner. Both soluble viral receptor proteins bound to the VP0 and VP1 capsid proteins of CVB3. The in vivo efficacy of viral receptor proteins was evaluated by intramuscular injection of plasmid (hCAR:Fc or hCAR-hDAF:Fc) followed by electroporation in a murine model of CVB3 myocarditis. Serum levels of the virus receptor proteins increased relative to baseline values from day 3 and peaked on day 14 at 12.9-fold for hCAR:Fc and 7.1-fold for hCAR-hDAF:Fc. The 3-week survival rate was significantly higher in hCAR-hDAF:Fc-treated mice (61%) than in hCAR:Fc-treated mice (29%) and in controls (15%; p