Non-autonomous overgrowth triggered by vps25 and tsg101 loss of function has been attributed to upregulated cytokine secretion, following autonomous activation of the Notch signalling pathway in the mutant cells. We have also observed an activation of Notch signalling and cell non-autonomous hyperplastic growth in tissues flanking dVps4-IR-expressing cells, suggesting that non-autonomous stimulation of proliferation may be a common feature of ESCRT deficiency. We suggest that both the non-cell-autonomous and the cell autonomous FMK effects of dVps4 disruption contribute to tumourigenesis. In conclusion, we have shown that the ESCRT-III regulator dVps4 is crucial for attenuation of signalling pathways that mediate cell-autonomous apoptosis, actin rearrangement, integrin upregulation, MMP1 upregulation and loss of polarity. With exception of the latter, all these effects can be attributed, entirely or partially, to activation of JNK. Further studies aimed at clarifying the mechanistic relationship between dVps4 inactivation and JNK activation will be required in order to fully understand the tumour suppressor function of dVps4. Coxsackievirus B3 is a single stranded, positive sense RNA virus that is one of the major etiological viral agents of human myocarditis and dilated cardiomyopathy. The virus also rapidly infects the myocardium of mice, reaching peak viral titers within 3�C4 days and then declining in the heart until eliminated, usually within 10�C14 days. Viral elimination depends upon several distinct host defense mechanisms including type I interferons, T cell response to CVB3, virus neutralizing antibody, and activated macrophages. Several reports show that blocking type I IFN, either by injection of anti-interferon antibodies or use of IFN receptor a/b-deficient mice, results in greater viral burden and mortality, whereas administration of exogenous type I IFN ameliorates the disease. Although early inflammatory responses are important for resolution of virus infection, there is accumulating evidence to indicate that the Darifenacin hydrobromide cellular inflammatory infiltrate following viral infection is directly associated with disease severity in experimental models of viral myocarditis. High numbers of lymphocytes persisting in the myocardium can lead to exacerbation of disease. Thus, a delicate balance between the beneficial and detrimental effects of the immune response must be established to promote efficient protection.