Human respiratory syncytial virus (hRSV) is a leading cause of acute lower respiratory tract infection in infants, elderly and immunocompromised individuals. To date, no specific antiviral drug is available to treat or prevent this disease. Here, we report that the Smoothened receptor (Smo) antagonist cyclopamine acts as a potent and selective inhibitor of in vitro and in vivo hRSV replication. Cyclopamine inhibits hRSV through a novel, Smo-independent mechanism. It specifically impairs the function of the hRSV RNA-dependent RNA polymerase complex notably by reducing expression levels of the viral anti-termination factor M2-1. The relevance of these findings is corroborated by the demonstration that a single R151K mutation in M2-1 is sufficient to confer virus resistance to cyclopamine in vitro and that cyclopamine is able to reduce virus titers in a mouse model of hRSV infection. The results of our study open a novel avenue for the development of future therapies against hRSV infection.

A significant problem affecting gene therapy approaches aiming at achieving long-term transgene expression is the immune response against the protein product of the therapeutic gene, which can reduce or eliminate the therapeutic effect. The problem is further exacerbated when therapy involves targeting an immunogenic tissue and/or one with a pre-existing inflammatory phenotype, such as dystrophic muscles. In this proof-of-principle study, we co-expressed a model antigen, bacterial β-galactosidase, with an immunosuppressive factor, indoleamine 2,3-dioxygenase 1 (IDO1), in muscles of the mdx mouse model of Duchenne muscular dystrophy. This treatment prevented loss of expression of the transgene concomitant with significantly elevated expression of T-regulatory (Treg) markers in the IDO1-expressing muscles. Moreover, co-expression of IDO1 resulted in reduced serum levels of anti-β-gal antibodies. These data indicate that co-expression of genes encoding immunomodulatory enzymes controlling kynurenine pathways provide a viable strategy for preventing loss of transgenes targeted into dystrophic muscles with pre-existing inflammation.

Historical transparent glass is a fragile and challenging material. Deterioration of historical glass objects kept in presence of volatile organic compounds (VOCs) mainly formaldehyde, formic acid and acetic acid, is a known phenomenon. Similar issues were encountered with glass objects in the collection centre of the Swiss National Museum, belonging to 17 th -20 th century CE. Until 1999, these objects were stored in chipwood mobile shelving units (a source of VOCs) in conditions with fluctuating relative humidity (RH) levels and temperature. To study this phenomenon, model glasses were produced and subjected to accelerated aging with variable relative humidity and in the presence of acetic acid and formic acid. The aged samples were documented using digital techniques such as digital photography, reflectance transformation imaging, optical microscopy, and hyperspectral Imaging (HSI) to assess changes in their appearance and to detect early signs of corrosion. The results from the application of multi-modal imaging techniques to visualize the surface of transparent colourless glass show promise for the documentation of VOC induced corrosion phenomena on glass surfaces.