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Structural Basis and Evolution of Glycan Receptor Specificities within the Polyomavirus Family.
mBio
July 2020
Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
Asymptomatic infections with polyomaviruses in humans are common, but these small viruses can cause severe diseases in immunocompromised hosts. New Jersey polyomavirus (NJPyV) was identified via a muscle biopsy in an organ transplant recipient with systemic vasculitis, myositis, and retinal blindness, and human polyomavirus 12 (HPyV12) was detected in human liver tissue. The evolutionary origins and potential diseases are not well understood for either virus.
View Article and Find Full Text PDFDivalent Sialylated Precision Glycooligomers Binding to Polyomaviruses and the Effect of Different Linkers.
Macromol Biosci
May 2019
Institute of Organic and Macromolecular Chemistry, Heinrich-Heine-University Duesseldorf, Universitaetsstrasse 1, 40225, Duesseldorf, Germany.
Divalent precision glycooligomers terminating in N-acetylneuraminic acid (Neu5Ac) or 3'-sialyllactose (3'-SL) with varying linkers between scaffold and the glycan portions are synthesized via solid phase synthesis for co-crystallization studies with the sialic acid-binding major capsid protein VP1 of human Trichodysplasia spinulosa-associated Polyomavirus. High-resolution crystal structures of complexes demonstrate that the compounds bind to VP1 depending on the favorable combination of carbohydrate ligand and linker. It is found that artificial linkers can replace portions of natural carbohydrate linkers as long as they meet certain requirements such as size or flexibility to optimize contact area between ligand and receptor binding sites.
View Article and Find Full Text PDFThe Human Polyomavirus Middle and Alternative T-Antigens; Thoughts on Roles and Relevance to Cancer.
Front Microbiol
March 2018
Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands.
Approximately 15-20% of human cancer is related to infection, which renders them potentially preventable by antimicrobial or antiviral therapy. Human polyomaviruses (PyVs) are relevant in this regard, as illustrated by the involvement of Merkel cell polyomavirus (MCPyV) in the development of Merkel cell carcinoma. The polyomavirus Small and Large tumor antigen (ST and LT) have been extensively studied with respect to their role in oncogenesis.
View Article and Find Full Text PDFDysregulation of the MEK/ERK/MNK1 signalling cascade by middle T antigen of the trichoydsplasia spinulosa polyomavirus.
J Eur Acad Dermatol Venereol
August 2017
Department of Dermatology, McGovern Medical School at Houston, Houston, TX, USA.
Background: Trichodysplasia spinulosa (TS) is a disfiguring folliculocentric cutaneous disease caused by infection with the trichodysplasia spinulosa polyomavirus (TSPyV). The TSPyV genome contains splice variants encoding the middle tumour (mT) antigen, although the potential role for TSPyV mT antigen in disease development remains unknown.
Objective: The current study was designed to investigate the mechanistic properties of TSPyV mT antigen, which may further our understanding of TS pathogenesis and provide insight into potential therapies.
Cutaneous Human Polyomavirus Small T Antigens and 4E-BP1 Targeting.
Intervirology
December 2017
Department of Dermatology, University of Texas Medical School at Houston, Houston, Tex., USA.
Merkel cell polyomavirus (MCPyV), trichodysplasia spinulosa-associated polyomavirus (TSPyV), human polyomavirus 6 (HPyV6), and human polyomavirus 7 (HPyV7) are implicated in the pathogeneses of distinct hyperproliferative cutaneous growths and encode small tumor (sT) antigens. The current study demonstrates that the four sT antigens differentially regulate 4E-binding protein 1 (4E-BP1) serine 65 hyperphosphorylation. MCPyV and HPyV7 sT antigens were found to promote the presence of the hyperphosphorylated 4E-BP1-δ isoform, while TSPyV and HPyV6 sT antigens had no significant effects.
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