| 1. |
- Nasir, Waqas, et al.
(författare)
-
Lewis histo-blood group alpha1,3/alpha1,4 fucose residues may both mediate binding to GII.4 noroviruses
- 2012
-
Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 22:9, s. 1163-72
-
Tidskriftsartikel (refereegranskat)abstract
- Human noroviruses cause recurrent epidemics of gastroenteritis known to be dominated by the clinically important GII.4 genotype which recognizes human Secretor gene-dependent ABH histo-blood group antigens (HBGAs) as attachment factors. There is increasing evidence that GII.4 noroviruses have undergone evolutionary changes to recognize Lewis antigens and non-Secretor saliva. In this study, we have investigated the possibilities of the Lewis alpha1,3/alpha1,4 fucoses as mediators of binding of GII.4 noroviruses to Lewis antigens. The study was carried out using molecular dynamics simulations of Lewis type-1 and type-2 chain HBGAs in complex with VA387 P domain dimers in explicit water. Based on the computer simulations, we suggest the possibility of two receptor binding modes for Lewis HBGAs: the "Secretor pose" with the Secretor Fucalpha1,2 in the binding site and the "Lewis pose" with the Lewis Fucalpha1,3/alpha1,4 residues in the binding site. This was further supported by an extensive GlyVicinity analysis of the Protein Data Bank with respect to the occurrence of the Lewis and Secretor poses in complexes of Lewis antigens with lectins and antibodies as well as GII norovirus strains. The Lewis pose can also explain the interactions of GII.4 norovirus strains with Le(x) and SLe(x) structures. Moreover, the present model suggests binding of complex branched polysaccharides, with the Lewis antigens at the nonreducing end, to P domain dimers of GII.4 strains. Our results are relevant for understanding the evolution of norovirus binding specificities and for in silico design of future antiviral therapeutics.
|
|
| 2. |
- Bally, Marta, 1981, et al.
(författare)
-
Interaction of virions with membrane glycolipids
- 2012
-
Ingår i: Physical Biology. - : IOP Publishing. - 1478-3967 .- 1478-3975. ; 9:2
-
Tidskriftsartikel (refereegranskat)abstract
- Cellular membranes contain various lipids including glycolipids (GLs). The hydrophilic head groups of GLs extend from the membrane into the aqueous environment outside the cell where they act as recognition sites for specific interactions. The first steps of interaction of virions with cells often include contacts with GLs. To clarify the details of such contacts, we have used the total internal reflection fluorescence microscopy to explore the interaction of individual unlabelled virus-like particles (or, more specifically, norovirus protein capsids), which are firmly bound to a lipid bilayer, and fluorescent vesicles containing glycosphingolipids (these lipids form a subclass of GLs). The corresponding binding kinetics were earlier found to be kinetically limited, while the detachment kinetics were logarithmic over a wide range of time. Here, the detachment rate is observed to dramatically decrease with increasing concentration of glycosphingolipids from 1% to 8%. This effect has been analytically explained by using a generic model describing the statistics of bonds in the contact area between a virion and a lipid membrane. Among other factors, the model takes the formation of GL domains into account. Our analysis indicates that in the system under consideration, such domains, if present, have a characteristic size smaller than the contact area between the vesicle and the virus-like particle.
|
|
| 3. |
- Bally, Marta, 1981, et al.
(författare)
-
Interaction of Single Viruslike Particles with Vesicles Containing Glycosphingolipids
- 2011
-
Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 107:18
-
Tidskriftsartikel (refereegranskat)abstract
- Glycosphingolipids are involved in the first steps of virus-cell interaction, where they mediate specific recognition of the host cell membrane. We have employed total-internal-reflection fluorescence microscopy to explore the interaction kinetics between individual unlabeled noroviruslike particles, which are attached to a glycosphingolipid-containing lipid bilayer, and fluorescent vesicles containing different types and concentrations of glycosphingolipids. Under association equilibrium, the vesicle-binding rate is found to be kinetically limited, yielding information on the corresponding activation energy. The dissociation kinetics are logarithmic over a wide range of time. The latter is explained by the vesicle-size-related distribution of the dissociation activation energy. The biological, pharmaceutical, and diagnostic relevance of the study is briefly discussed.
|
|
| 4. |
- Thorstenson, Sten, et al.
(författare)
-
Implementation of large‑scale routine diagnostics using whole slide imaging in Sweden: Digital pathology experiences 2006-2013
- 2014
-
Ingår i: Journal of Pathology Informatics. - : Elsevier BV. - 2229-5089 .- 2153-3539. ; 5:14
-
Tidskriftsartikel (refereegranskat)abstract
- Recent technological advances have improved the whole slide imaging (WSI) scanner quality and reduced the cost of storage, thereby enabling the deployment of digital pathology for routine diagnostics. In this paper we present the experiences from two Swedish sites having deployed routine large-scale WSI for primary review. At Kalmar County Hospital, the digitization process started in 2006 to reduce the time spent at the microscope in order to improve the ergonomics. Since 2008, more than 500,000 glass slides have been scanned in the routine operations of Kalmar and the neighboring Linköping University Hospital. All glass slides are digitally scanned yet they are also physically delivered to the consulting pathologist who can choose to review the slides on screen, in the microscope, or both. The digital operations include regular remote case reporting by a few hospital pathologists, as well as around 150 cases per week where primary review is outsourced to a private clinic. To investigate how the pathologists choose to use the digital slides, a web-based questionnaire was designed and sent out to the pathologists in Kalmar and Linköping. The responses showed that almost all pathologists think that ergonomics have improved and that image quality was sufficient for most histopathologic diagnostic work. 38 ± 28% of the cases were diagnosed digitally, but the survey also revealed that the pathologists commonly switch back and forth between digital and conventional microscopy within the same case. The fact that two full-scale digital systems have been implemented and that a large portion of the primary reporting is voluntarily performed digitally shows that large-scale digitization is possible today.
|
|
