The tyrosine kinase p56lck is essential in coxsackievirus B3-mediated heart disease.
Infections are thought to be important in the pathogenesis of many heart diseases. Coxsackievirus B3 (CVB3) has been linked to chronic dilated cardiomyopathy, a common cause of progressive heart disease, heart failure and sudden death. We show here that the sarcoma (Src) family kinase Lck (p56lck) is required for efficient CVB3 replication in T-cell lines and for viral replication and persistence in vivo. Whereas infection of wild-type mice with human pathogenic CVB3 caused acute and very severe myocarditis, meningitis, hepatitis, pancreatitis and dilated cardiomyopathy, mice lacking the p56lck gene were completely protected from CVB3-induced acute pathogenicity and chronic heart disease. These data identify a previously unknown function of Src family kinases and indicate that p56lck is the essential host factor that controls the replication and pathogenicity of CVB3.
Liu
P
P
Heart and Stroke/Lewar Centre of Excellence in Cardiovascular Research, University of Toronto, University Health Network, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
Aitken
K
K
Kong
Y Y
YY
Opavsky
M A
MA
Martino
T
T
Dawood
F
F
Wen
W H
WH
Kozieradzki
I
I
Bachmaier
K
K
Straus
D
D
Mak
T W
TW
Penninger
J M
JM
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002908:Chronic Disease; D003384:Coxsackievirus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D004686:Encephalomyocarditis virus / Q000472:pathogenicity; D029822:Enterovirus B, Human / Q000472:pathogenicity* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D014779:Virus Replication; D019061:src-Family Kinases / Q000378:metabolism
D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases