Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a nucleocytoplasmic shuttling protein that regulates gene expression through its action on mRNA metabolism and translation. The cytoplasmic redistribution of hnRNP A1 is a regulated process during viral infection and cellular stress. Here, we show that hnRNP A1 is an internal ribosome entry site (IRES) trans-acting factor that binds specifically to the 5 untranslated region of both the human rhinovirus-2 and the human apoptotic peptidase activating factor 1 (apaf-1) mRNAs, thereby regulating their translation. Furthermore, the cytoplasmic redistribution of hnRNP A1 after rhinovirus infection leads to enhanced rhinovirus IRES-mediated translation, whereas the cytoplasmic relocalization of hnRNP A1 after UVC irradiation limits the UVC-triggered translational activation of the apaf-1 IRES. Therefore, this study provides a direct demonstration that IRESs behave as translational enhancer elements regulated by specific trans-acting mRNA binding proteins in given physiological conditions. Our data highlight a new way to regulate protein synthesis in eukaryotes through the subcellular relocalization of a nuclear mRNA-binding protein.

The diagnosis of acute myocarditis is complex and challenging. The use of the Dallas criteria in the diagnosis of myocarditis is associated with poor sensitivity and specificity because of the sampling error related to the often focal distribution of the specific histological lesions in cardiac tissue and the variability in pathological interpretation. To improve histological diagnosis, additional virological evaluation of cardiac tissues is required, with immunohistochemical and polymerase chain reaction (PCR) techniques allowing identification and quantification of viral infection markers. The diagnostic gold standard is endomyocardial biopsy (EMB) with the histological Dallas criteria, in association with new immunohistochemical and PCR analyses of cardiac tissues. Using real-time PCR and reverse transcription PCR assays, parvovirus B19, Coxsackie B virus, human herpesvirus 6 (HHV-6) type B and adenovirus have been detected in 37, 33, 11 and 8% of EMB, respectively, from young adults (aged<35 years) with histologically proven acute myocarditis. Viral co-infections have also been found in 12% of acute myocarditis cases, generally parvovirus B19 plus HHV-6. Moreover, herpesviruses such as the Epstein-Barr virus or cytomegalovirus can also be associated with myocarditis after heart transplantation. During the clinical course of myocarditis, the immunohistochemical detection of enterovirus, adenovirus or parvovirus B19 capsid proteins or herpesvirus late proteins is necessary to differentiate a viral cardiac infection with replication activities from a persistent or latent cardiac infection. These new viral diagnostic approaches can lead to better identification of the aetiology of myocarditis and may therefore enable the development and evaluation of specific aetiology-directed treatment strategies.