20 research outputs found
Essential Roles for Soluble Virion-Associated Heparan Sulfonated Proteoglycans and Growth Factors in Human Papillomavirus Infections
A subset of human papillomavirus (HPV) infections is causally related to the development of human epithelial tumors and cancers. Like a number of pathogens, HPV entry into target cells is initiated by first binding to heparan sulfonated proteoglycan (HSPG) cell surface attachment factors. The virus must then move to distinct secondary receptors, which are responsible for particle internalization. Despite intensive investigation, the mechanism of HPV movement to and the nature of the secondary receptors have been unclear. We report that HPV16 particles are not liberated from bound HSPG attachment factors by dissociation, but rather are released by a process previously unreported for pathogen-host cell interactions. Virus particles reside in infectious soluble high molecular weight complexes with HSPG, including syndecan-1 and bioactive compounds, like growth factors. Matrix mellatoproteinase inhibitors that block HSPG and virus release from cells interfere with virus infection. Employing a co-culture assay, we demonstrate HPV associated with soluble HSPG-growth factor complexes can infect cells lacking HSPG. Interaction of HPV-HSPG-growth factor complexes with growth factor receptors leads to rapid activation of signaling pathways important for infection, whereas a variety of growth factor receptor inhibitors impede virus-induced signaling and infection. Depletion of syndecan-1 or epidermal growth factor and removal of serum factors reduce infection, while replenishment of growth factors restores infection. Our findings support an infection model whereby HPV usurps normal host mechanisms for presenting growth factors to cells via soluble HSPG complexes as a novel method for interacting with entry receptors independent of direct virus-cell receptor interactions
Long term oral terazosin medication can be a safe and succesful treatment in children with neurogenic non-neurogenic bladder dysfunction
Atmospheric response to sea surface temperature mesoscale structures
International audienceRecent studies have revealed that strong sea surface temperature (SST) fronts, on the scale of a Western Boundary Current, significantly affect not just the Marine Boundary Layer but the entire troposphere. This has aroused renewed interest in air-sea interactions. The present study investigates the atmospheric response to fixed SST anomalies associated with mesoscale oceanic eddies and submesoscale filaments, using idealized simulations. Our main result is that in weak wind conditions, the vertical velocity in the planetary boundary layer (PBL) is linearly proportional to the SST Laplacian. This is established by a quantitative analysis in the spatial space as well as in the spectral space. Comparing the responses to two different SST fields shows that vertical velocities are much more intense when the submesoscales are more energetic. These results hold for different configurations of the atmospheric large-scale state and for different PBL parameterizations. Surface winds play the role of low-pass filter and reduce the response at the smaller scales. To our knowledge, this study is the first to clearly reveal the high impact of oceanic submesoscales on the atmospheric boundary layer at midlatitudes, as well as the direct link between the vertical velocity and the SST Laplacian
Long term oral terazosin medication can be a safe and succesful treatment in children with neurogenic non-neurogenic bladder dysfunction
6-O sulfated and N-sulfated Syndecan-1 promotes baculovirus binding and entry into mammalian cells.
Baculoviruses are insect-specific viruses commonly found in nature. They are not able to replicate in mammalian cells but can transduce them when equipped with an appropriate mammalian cell active expression cassette. Although the viruses have been studied in several types of mammalian cells from different origins, the receptor that baculovirus uses to enter or interact with mammalian cells has not yet been identified. Due to the wide tropism of the virus, the receptor has been suggested to be a generally found cell surface molecule. In this article, we investigated the interaction of baculovirus and mammalian cell surface heparan sulfate proteoglycans (HSPG) in more detail. Our data show that baculovirus requires HSPG sulfation, particularly N- and 6-O-sulfation, to bind to and transduce mammalian cells. According to our results, baculovirus binds specifically to syndecan-1 (SDC-1) but does not interact with SDC-2 to SDC-4 or with glypicans. Competition experiments performed with SDC-1 antibody or recombinant SDC-1 protein inhibited baculovirus binding, and SDC-1 overexpression enhanced baculovirus-mediated transduction. In conclusion, we show that SDC-1, a commonly found cell surface HSPG molecule, has a role in the binding and entry of baculovirus in vertebrate cells. The results presented here reveal important aspects of baculovirus entry and can serve as a basis for next-generation baculovirus vector development for gene delivery.peerReviewe