The hr1 and Fusion Peptide Regions of the Subgroup B Avian Sarcoma and Leukosis Virus Envelope Glycoprotein Influence Low pH-Dependent Membrane Fusion

The avian sarcoma and leukosis virus (ASLV) envelope glycoprotein (Env) is activated to trigger fusion by a two-step mechanism involving receptor-priming and low pH fusion activation. In order to identify regions of ASLV Env that can regulate this process, a genetic selection method was used to identify subgroup B (ASLV-B) virus-infected cells resistant to low pH-triggered fusion when incubated with cells expressing the cognate TVB receptor. The subgroup B viral Env (envB) genes were then isolated from these cells and characterized by DNA sequencing. This led to identification of two frequent EnvB alterations which allowed TVB receptor-binding but altered the pH-threshold of membrane fusion activation: a 13 amino acid deletion in the host range 1 (hr1) region of the surface (SU) EnvB subunit, and the A32V amino acid change within the fusion peptide of the transmembrane (TM) EnvB subunit. These data indicate that these two regions of EnvB can influence the pH threshold of fusion activation

Insulin Degrading Enzyme Induces a Conformational Change in Varicella-Zoster Virus gE, and Enhances Virus Infectivity and Stability

Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for virus infectivity and binds to a cellular receptor, insulin-degrading enzyme (IDE), through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE) enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines

Identification of potential opinion leaders in child health promotion in Sweden using network analysis

Background: Opinion leaders are often local individuals with high credibility who can influence other people. Robust effects using opinion leaders in diffusing innovations have been shown in several randomized controlled trials, for example regarding sexually transmitted infections (STI), human immunodeficiency virus (HIV) prevention, mammography rates and caesarean birth delivery rates. In a Cochrane review 2010 it was concluded that the use of opinion leaders can successfully promote evidence-based practice. Thus, using opinion leaders within the public health sector might be one means to speed up the dissemination of health promoting and disease preventing innovations. Social network analysis has been used to trace and map networks, with focus on relationships and positions, in widely spread arenas and topics. The purpose of this study was to use social network analysis in order to identify potential opinion leaders at the arena of child health promotion in Sweden. Results: By using snowball technique a short e-mail question was spread in up to five links, starting from seven initially invited persons. This inquiry resulted in a network consisting of 153 individuals. The most often mentioned actors were researchers, public health officials and paediatricians, or a combination of these professions. Four single individuals were mentioned by five to seven other persons in the network. These individuals obviously possess qualities that make other professionals within the public health sector listen to and trust them. Conclusions: Social network analysis seemed to be a useful method to identify influential persons with high credibility, i.e. potential opinion leaders, at the arena of child health promotion in Sweden. If genuine opinion leaders could be identified directed measures can be carried out in order to spread new and relevant knowledge. This may facilitate for public health actors at the local, regional and national level to more rapidly progress innovations into everyday practice. However, effectiveness studies of opinion leaders in the public health sector still have to be performed. © 2012 Guldbrandsson et al.Art. No.: 424</p