Antiviral treatment with WIN 54 954 reduces mortality in murine coxsackievirus B3 myocarditis.

Abstract:

BACKGROUND:Coxsackieviruses B (CBVs) are dominant causative agents in myocarditis and are associated with pathogenesis is some cases of dilated cardiomyopathy, a clinical entity with a poor survival without heart transplantation. METHODS AND RESULTS:In vitro, the antiviral agent WIN 54 954 was shown to inhibit replication of CBV3 at a minimal inhibitory concentration value of 0.02 mg/L. Administration of WIN 54 954, 100 mg/kg BID PO, beginning on the day of infection resulted in complete protection from enteroviral mortality (P < .01). WIN 54 954 treatment did not abrogate the inflammatory reaction in the myocardium. No difference was found in the expression of surface lymphocyte subset markers. At 3 weeks, macrophages seemed to dominate the inflammatory reaction, regardless of treatment. There was no difference in CBV3 antibody titers, indicating that WIN 54 954 does not interfere with the development of protective immunity. Complement factors C3 and B were synthesized at a higher level during infection and correlated well with the degree of inflammatory reaction. CONCLUSIONS:The results show that WIN 54 954 is a potent antiviral agent with a highly significant effect on survival in CBV-induced myocarditis in the A/J mouse if treatment is started early. It is suggested that the reduction in mortality seen with WIN 54 954 administration is due to an inhibitory effect on virus replication in affected organs that does not interfere with cellular or humoral immunity.

journal_name

Circulation

journal_title

Circulation

authors

Fohlman J,Pauksen K,Hyypiä T,Eggertsen G,Ehrnst A,Ilbäck NG,Friman G

doi

10.1161/01.cir.94.9.2254

subject

Has Abstract

pub_date

1996-11-01 00:00:00

pages

2254-9

issue

9

eissn

0009-7322

issn

1524-4539

journal_volume

94

pub_type

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