Cardiac myocyte-specific expression of SOCS1 significantly increased mortality and myocardial injury in coxsackievirus-infected mice, whereas inhibition of SOCS1 protected against virus-induced cardiac injury.
Does inhibition of SOCS1 improve myocyte resistance to acute cardiac injury in coxsackievirus-infected mice?
Inhibition of SOCS1 in cardiac myocytes augments the host-cell antiviral system and increases resistance to enterovirus-induced acute cardiac injury.
p-value: p=<0.0001
Enteroviral infections of the heart are among the most commonly identified causes of acute myocarditis in children and adults and have been implicated in dilated cardiomyopathy. Although there is considerable information regarding the cellular immune response in myocarditis, little is known about innate signaling mechanisms within the infected cardiac myocyte that contribute to the host defense against viral infection. Here we show the essential role of Janus kinase (JAK) signaling in cardiac myocyte antiviral defense and a negative role of an intrinsic JAK inhibitor, the suppressor of cytokine signaling (SOCS), in the early disease process. Cardiac myocyte-specific transgenic expression of SOCS1 inhibited enterovirus-induced signaling of JAK and the signal transducers and activators of transcription (STAT), with accompanying increases in viral replication, cardiomyopathy, and mortality in coxsackievirus-infected mice. Furthermore, the inhibition of SOCS in the cardiac myocyte through adeno-associated virus-mediated (AAV-mediated) expression of a dominant-negative SOCS1 increased the myocyte resistance to the acute cardiac injury caused by enteroviral infection. These results indicate that strategies directed at inhibition of SOCS in the heart and perhaps other organs can augment the host-cell antiviral system, thus preventing viral-mediated end-organ damage during the early stages of infection.
Yasukawa et al. (2003) studied Enterovirus-induced cardiac injury (acute myocarditis). Cardiac myocyte-specific transgenic expression of SOCS1 / AAV-mediated dnSOCS1 vs. Wild-type littermates / AAV-LacZ was evaluated on Survival rate after CVB3 inoculation (p=<0.0001). Cardiac myocyte-specific expression of SOCS1 significantly increased mortality and myocardial injury in coxsackievirus-infected mice, whereas inhibition of SOCS1 protected against virus-induced cardiac injury.