Antiviral and myocyte protective effects of murine interferon-beta and -{alpha}2 in coxsackievirus B3-induced myocarditis and epicarditis in Balb/c mice.
The present study tested the hypothesis that murine (m)IFN-beta or mIFN-alpha(2) can eliminate cardiac viral load and protect cardiomyocytes from injury in animals infected with coxsackievirus B3 (CVB3). CVB3-inoculated male Balb/c mice exhibited signs of illness, including lethargy, progressive weight loss, and death (10% on day 3 and 100% on day 8). Cardiac viral load was high [4,277 +/- 1,009 plaque-forming units and 25 +/- 5 copies CVB3/hypoxanthine guanine phosphoribosyl transferase 1 mRNA] on day 4. The cardiac tissue exhibited severe inflammatory infiltration and myocyte damage with an average myocarditis integrated pathology score of 2.1 +/- 0.2 on day 7. Most of the mice infected with CVB3 also developed epicarditis, and 55% had intraventricular thrombi present. Treatment with mIFN-beta [2.5 to 10 million international units (MIU)/kg] dose-dependently improved the general health status in CVB3-inoculated mice, as evidenced by reduction in weight loss, prevention of death, elimination of cardiac viral load, protection of myocytes from injury, decrease in inflammatory cell infiltration, and attenuation of intraventricular thrombus formation. Treatment with 10 MIU/kg mIFN-alpha(2) resulted in a similar level of efficacy as that induced by 5 MIU/kg mIFN-beta, with the exception that mIFN-alpha(2) did not reduce cardiac CVB3 mRNA. However, mIFN-alpha(2) , but not any dose group of mIFN-beta, significantly attenuated CVB3-induced epicarditis. These data demonstrate antiviral effects for both mIFN-beta and mIFN-alpha(2), which lead to protection of the mice from CVB3-induced myocarditis. However, the potential mechanisms leading to a differential host response for the two isoforms of mIFN remain to be elucidated.
Wang
Yi-Xin
YX
Berlex Biosciences, Richmond, CA, USA. jim.wang@bayer.com
da Cunha
Valdeci
V
Vincelette
Jon
J
White
Kathy
K
Velichko
Sharlene
S
Xu
Yifan
Y
Gross
Cynthia
C
Fitch
Richard M
RM
Halks-Miller
Meredith
M
Larsen
Brent R
BR
Yajima
Toshitaka
T
Knowlton
Kirk U
KU
Vergona
Ronald
R
Sullivan
Mark E
ME
Croze
Ed
E
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage; D002316:Cardiotonic Agents / Q000008:administration & dosage; D002478:Cells, Cultured; D004770:Enterovirus / Q000187:drug effects*; D016898:Interferon-alpha / Q000008:administration & dosage*; D016899:Interferon-beta / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D032342:Muscle Cells / Q000187:drug effects / Q000821:virology; D009205:Myocarditis / Q000188:drug therapy* / Q000821:virology*; D010496:Pericardium / Q000187:drug effects* / Q000821:virology*; D016896:Treatment Outcome
D000998:Antiviral Agents; D002316:Cardiotonic Agents; D016898:Interferon-alpha; D016899:Interferon-beta