Coxsackievirus B3-associated myocardial pathology and viral load reduced by recombinant soluble human decay-accelerating factor in mice.
Coxsackievirus B3 (CVB3) infection can result in myocarditis, which in turn may lead to a protracted immune response and subsequent dilated cardiomyopathy. Human decay-accelerating factor (DAF), a binding receptor for CVB3, was synthesized as a soluble IgG1-Fc fusion protein (DAF-Fc). In vitro, DAF-Fc was able to inhibit complement activity and block infection by CVB3, although blockade of infection varied widely among strains of CVB3. To determine the effects of DAF-Fc in vivo, 40 adolescent A/J mice were infected with a myopathic strain of CVB3 and given DAF-Fc treatment 3 days before infection, during infection, or 3 days after infection; the mice were compared with virus alone and sham-infected animals. Sections of heart, spleen, kidney, pancreas, and liver were stained with hematoxylin and eosin and submitted to in situ hybridization for both positive-strand and negative-strand viral RNA to determine the extent of myocarditis and viral infection, respectively. Salient histopathologic features, including myocardial lesion area, cell death, calcification and inflammatory cell infiltration, pancreatitis, and hepatitis were scored without knowledge of the experimental groups. DAF-Fc treatment of mice either preceding or concurrent with CVB3 infection resulted in a significant decrease in myocardial lesion area and cell death and a reduction in the presence of viral RNA. All DAF-Fc treatment groups had reduced infectious CVB3 recoverable from the heart after infection. DAF-Fc may be a novel therapeutic agent for active myocarditis and acute dilated cardiomyopathy if given early in the infectious period, although more studies are needed to determine its mechanism and efficacy.
Yanagawa
Bobby
B
UBC McDonald Research Laboratories/The iCAPTUR E Centre, Department of Pathology and Laboratory Medicine, St. Paul's Hospital/Providence Health Care-University of British Columbia, Vancouver British Columbia, Canada.
Spiller
O Brad
OB
Choy
Jonathan
J
Luo
Honglin
H
Cheung
Paul
P
Zhang
Huifang M
HM
Goodfellow
Ian G
IG
Evans
David J
DJ
Suarez
Agripina
A
Yang
Decheng
D
McManus
Bruce M
BM
D000818:Animals; D018958:CD55 Antigens / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000517:prevention & control* / Q000821:virology; D003165:Complement System Proteins / Q000502:physiology; D029822:Enterovirus B, Human / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification*; D051379:Mice; D009206:Myocardium / Q000473:pathology*; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use; D019562:Viral Load; D010948:Viral Plaque Assay
D018958:CD55 Antigens; D012367:RNA, Viral; D011994:Recombinant Proteins; D003165:Complement System Proteins