Soluble recombinant coxsackievirus and adenovirus receptor abrogates coxsackievirus b3-mediated pancreatitis and myocarditis in mice.
BACKGROUND
Group B coxsackievirus infection can result in organ injury and inflammation. The coxsackievirus and adenovirus receptor (CAR) and decay-accelerating factor (DAF; CD55) have both been identified as receptors for coxsackievirus B3 (CVB3). We have shown elsewhere that early DAF-Fc treatment attenuates CVB3-induced myocarditis and virus replication.


METHODS
CAR was synthesized as a soluble IgG1-Fc fusion protein (CAR-Fc). In vitro, CAR-Fc blocked infection by 2 different strains of CVB3. A/J mice were infected in vivo with CVB3 and were administered CAR-Fc either 3 days before infection, during infection, or 3 days after infection and were compared with mice infected with virus alone and control animals.


RESULTS
All CAR-Fc treatment groups had reduced recoverable infectious virus in the heart. CAR-Fc treatment of mice, either preceding or concurrent with CVB3 infection, resulted in complete inhibition of myocardial lesion area, cell death and inflammation, and viral RNA. Early treatment also completely blocked inflammation and cell death in the pancreas, an organ that is normally very sensitive to infection.


CONCLUSIONS
To our knowledge, CAR-Fc is the only protein that has been shown to block coxsackievirus infection of the pancreas. However, regardless of the efficacy of the test protein, target tissue cannot be rescued after day 3 of infection in the A/J mouse model.
Yanagawa
Bobby
B
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Department of Pathology and Laboratory Medicine, St. Paul's Hospital/Providence Health Care-UBC, Vancouver, Canada.
Spiller
O Brad
OB
Proctor
David G
DG
Choy
Jonathan
J
Luo
Honglin
H
Zhang
Huifang M
HM
Suarez
Agripina
A
Yang
Decheng
D
McManus
Bruce M
BM
D000818:Animals; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003588:Cytopathogenic Effect, Viral / Q000276:immunology; D029822:Enterovirus B, Human / Q000235:genetics / Q000276:immunology*; D006651:Histocytochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000821:virology; D008099:Liver / Q000821:virology; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000188:drug therapy / Q000821:virology*; D009500:Neutralization Tests; D010195:Pancreatitis / Q000188:drug therapy / Q000821:virology*; D011897:Random Allocation; D011991:Receptors, Virus / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D013154:Spleen / Q000821:virology; D014779:Virus Replication / Q000276:immunology
C568771:CLMP protein, human; C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; D011994:Recombinant Proteins