Respiratory Syncytial Virus (RSV) is the major cause of acute bronchiolitis in infants under 2 years old. Necroptosis has been implicated in the outcomes of respiratory virus infections. Here we report that RSV infection triggers necroptosis in primary mouse macrophages and human monocytes in a RIPK1-, RIPK3-, and MLKL-dependent manner. Moreover, necroptosis pathways are harmful to RSV clearance from alveolar macrophages. Additionally, Ripk3-/- mice were protected from RSV-induced weight loss and presented reduced viral loads in the lungs.Alveolar macrophage depletion also protected mice from weight loss and decreased lung RSV virus load. Importantly, alveolar macrophage depletion abolished the upregulation of Ripk3 and Mlkl gene expression induced by RSV infection in the lung tissue.Autocrine TNF mediated RSV-triggered macrophage necroptosis and necroptosis pathways were also involved in TNF secretion even when macrophages were committed to cell death, which can worsen lung injury during RSV infection. In line, Tnfr1-/- mice had a marked decrease in Ripk3 and Mlkl gene expression and a sharp reduction in the numbers of necrotic alveolar macrophages in the lungs. Finally, we provide evidence that elevated nasal levels of TNF are associated with disease severity in infants with RSV bronchiolitis.We propose that targeting TNF and/or the necroptotic machinery may be valuable as therapeutic approaches to reduce the respiratory morbidity caused by RSV infection in young children.

A systematic pharmacological examination has been made of 55 Jamaican plants, most of which have a local reputation as medicinals. A number of interesting, but no outstanding, activities were observed. The results are tabulated.

The constituents of the heartwood of Cedrela odorata are variable. The structure of methyl angolensate, one of the components, is elucidated on the basis of spectroscopic evidence and chemical transformations. It is a secoring-I3 tetranortriterpenoid closely related biogenetically to gedunin and deacetyl-7-keto-gedunin, which are also found in the heartwood.

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