The Ribosome Binding Site of Hepatitis C Virus mRNA

Hepatitis C virus (HCV) infects an estimated 170 million people worldwide, the majority of whom develop a chronic infection which can lead to severe liver disease, and for which no generally effective treatment yet exists. A promising target for treatment is the internal ribosome entry site (IRES) of HCV, a highly conserved domain within a highly variable RNA. Never before have the ribosome binding sites of any IRES domains, cellular or viral, been directly characterized. Here, we reveal that the HCV IRES sequences most closely associated with 80S ribosomes during protein synthesis initiation are a series of discontinuous domains together comprising by far the largest ribosome binding site yet discovered.     

Mycosides C: Behavior as Receptor Site Substance for Mycobacteriophage D4

Interpretation of an earlier published infrared spectrum of Mycobacterium smegmatis lipids with receptor site activity for D4 phage led us to the inference that the active substance is very likely a mycoside C. This hypothesis was confirmed: the well-characterized mycosides C(s) and C(1217) elaborated by the heterologous strains M. scrofulaceum and Mycobacterium species 1217, respectively, are essentially indistinguishable from the smegmatis lipids in their behavior toward D4. Minute quantities adsorb and extensively inactivate the phage on appropriate incubations. In accord with derivative expectations, Mycobacterium species 1217 is a permissive host, attacked and lysed by D4. However, our current strains of M. butyricum, M. avium, and M. scrofulaceum, which reputedly produce various related mycosides C, are neither lysed by nor do they significantly adsorb the phage. Implications of these observations are discussed.