CD81-Receptor Associations — Impact for Hepatitis C Virus Entry and Antiviral Therapies

Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into host cells, including hepatitis C virus (HCV) entry into hepatocytes. HCV is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV entry into hepatocytes is a complex process that requires the coordinated interaction of viral and host factors for the initiation of infection, including CD81, scavenger receptor BI, claudin-1, occludin, membrane-bound host cell kinases, Niemann-Pick C1 Like 1, Harvey rat sarcoma viral oncogene homolog (HRas), CD63 and transferrin receptor 1. Furthermore, recent data in HCV model systems have demonstrated that targeting critical components of tetraspanins and associated cell membrane proteins open new avenues to prevent and treat viral infection.     

Left Main Coronary Atresia in a Child with Absent Pulmonary Valve Syndrome: Early Entrapment of an Innocent Bystander

Atresia of the left main coronary artery is a rare anomaly that, if left untreated, has an unfavorable outcome. We hereby report left main coronary artery atresia in a child with tetralogy of Fallot with absent pulmonary valve and discuss the possible developmental basis of the association.     

Autophagy mediates transporter associated with antigen processing-independent presentation of viral epitopes through MHC class I pathway

The endogenous presentation of the majority of viral epitopes through MHC class I pathway is strictly dependent on the transporter associated with antigen processing (TAP) complex, which transfers the peptide products of proteasomal degradation into the endoplasmic reticulum. A small number of epitopes can be presented through the TAP-independent pathway, the precise mechanism for which remains largely unresolved. Here we show that TAP-independent presentation can be mediated by autophagy and that this process uses the vacuolar pathway and not the conventional secretory pathway. After macroautophagy, the antigen is processed through a proteasome-independent pathway, and the peptide epitopes are loaded within the autophagolysosomal compartment in a process facilitated by the relative acid stability of the peptide-MHC interaction. Despite bypassing much of the conventional MHC class I pathway, the autophagy-mediated pathway generates the same epitope as that generated through the conventional pathway and thus may have a role in circumventing viral immune evasion strategies that primarily target the conventional pathway.