Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus

Gangliosides serve as receptors for internalization and infection by members of the polyomavirus family. Specificity is determined by recognition of carbohydrate moieties on the ganglioside by the major viral capsid protein VP1. For the mouse polyomavirus (MuPyV), gangliosides with terminal sialic acids in specific linkages are essential. Although many biochemical and cell culture experiments have implicated gangliosides as MuPyV receptions, the role of gangliosides in the MuPyV-infected mouse has not been investigated. Here we report results of studies using ganglioside-deficient mice and derived cell lines. Knockout mice lacking complex gangliosides were completely resistant to the cytolytic and pathogenic effects of the virus. Embryo fibroblasts from these mice were likewise resistant to infection, and supplementation with specific gangliosides restored infectibility. Although lacking receptors for viral infection, cells from ganglioside-deficient mice retained the ability to respond to the virus. Ganglioside-deficient fibroblasts responded rapidly to virus exposure with a transient induction of c-fos as an early manifestation of a mitogenic response. Additionally, splenocytes from ganglioside-deficient mice responded to MuPyV by secretion of IL-12, previously recognized as a key mediator of the innate immune response. Thus, while gangliosides are essential for infection in the animal, gangliosides are not required for mitogenic responses and innate immune responses to the virus

Acceptability of a Positive Parenting Programme on a Mother and Baby Unit: Q-Methodology with Staff

The Baby Triple P Positive Parenting Programme, a new addition to the established Triple P programmes, is currently being considered for a trial in a Mother and Baby Unit with the aim of exploring its benefits to mothers presenting with severe mental illness. The aim of the current study was to investigate staff views of the acceptability and feasibility of a parenting programme such as the Baby Triple P Positive Parenting Programme in a Mother and Baby Unit. Q-methodology, using an 88-item Q-sort, was employed to explore the opinions of 16 staff working in a Mother and Baby Unit in the North West of England. Results obtained from the Q-sort analysis identified two distinct factors: (1) staff qualified acceptance and (2) systemic approach/systemic results. Preliminary findings indicate that staff perceived Baby Triple P to be an acceptable and feasible intervention for the Mother and Baby Unit setting and that mothers on the unit would be open and receptive to the programme. Further research is required to expand these findings and assess the potential for this type of intervention to be used more widely across a number of Mother and Baby Unit settings

Overview and biosynthetic pathway of the four most prominent ganglioside series.

<p>The glycan parts of important members are shown for each series. The downstream biosynthetic steps are identical for all members of a row, although they may vary in linkage orientation. The six-membered pyranose rings are numbered counterclockwise, starting from the bottom (C1, except for C2 in Neu5Ac), and the ring oxygen is symbolized with a black dot. Neu5Ac moieties are rearranged for clarity, and all linkages are mediated by O2 or O8. Most of the gangliosides (e.g. LM1) can be further modified, e.g. by fucosylation. Linkages involving Neu5Ac are present in the α conformation, all other linkages are in the β conformation. Boxes represent three distinguishable sialoglycotopes that contain linkages found in GT1a (blue, representative for [α-2,8]), GD1a (green, [α-2,3]), and 3’-6’-iso-LD1 (also referred to as DSLNT, orange, [α-2,6]). The naming is according to the corresponding gangliosides; if possible, the Svennerholm shorthand is used [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref064" target="_blank">64</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref066" target="_blank">66</a>] All biosynthetic routes were verified using the KEGG metabolic pathway database [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref067" target="_blank">67</a>]. A prototype glycan that exemplifies the different positions of Gal and Neu5Ac moieties is depicted on the lower right. The glycan portions investigated in this study are highlighted by purple boxes.</p

Data collection and refinement statistics.

<p>Data collection and refinement statistics.</p

Description of the investigated MuPyV strains.

<p>Description of the investigated MuPyV strains.</p

The MuPyV binding pocket.

<p>Top view on the receptor-binding region of PTA, which is shown with E91 and V296 highlighted in salmon. Residues that are known to participate in receptor binding are contributed by the BC and HI loops and are highlighted as stick models. One monomer is shaded in green and the other monomers are alternatingly shaded light and dark grey for better distinction.</p

IL-12 response to MuPyV by splenocytes in KO mice.

<p>IL-12 response to MuPyV by splenocytes in KO mice.</p