دورية أكاديمية
أعرض في EDS

Novel Flavivirus Attenuation Markers Identified in the Envelope Protein of Alfuy Virus.

التفاصيل البيبلوغرافية
العنوان: Novel Flavivirus Attenuation Markers Identified in the Envelope Protein of Alfuy Virus.
المؤلفون: Westlake D; School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland 4072, Australia., Bielefeldt-Ohmann H; School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Queensland 4072, Australia.; School of Veterinary Sciences, The University of Queensland, Queensland 4072, Australia., Prow NAA; School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Queensland 4072, Australia.; Experimental Therapeutics Laboratory, School of Clinical and Health Sciences, University of South Australia Cancer Research Institute, Adelaide 5000, Australia., Hall RAA; School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Queensland 4072, Australia.
المصدر: Viruses [Viruses] 2021 Jan 20; Vol. 13 (2). Date of Electronic Publication: 2021 Jan 20.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Encephalitis Virus, Murray Valley/*pathogenicity , Encephalitis Viruses, Japanese/*pathogenicity , Encephalitis, Arbovirus/*virology , Flavivirus Infections/*virology , Viral Envelope Proteins/*chemistry , Viral Envelope Proteins/*metabolism, Amino Acid Motifs ; Animals ; Brain/pathology ; Brain/virology ; Cell Line ; Encephalitis Virus, Murray Valley/chemistry ; Encephalitis Virus, Murray Valley/metabolism ; Encephalitis Viruses, Japanese/chemistry ; Encephalitis Viruses, Japanese/growth & development ; Encephalitis Viruses, Japanese/metabolism ; Encephalitis, Arbovirus/pathology ; Flavivirus Infections/pathology ; Glycosaminoglycans/metabolism ; Glycosylation ; Heparin/pharmacology ; Mice ; Mutation ; Protein Domains ; Serial Passage ; Viral Envelope Proteins/genetics ; Viral Plaque Assay ; Virulence
مستخلص: Alfuy (ALFV) is an attenuated flavivirus related to the Murray Valley encephalitis virus (MVEV). We previously identified markers of attenuation in the envelope (E) protein of the prototype strain (ALFV 3929 ), including the hinge region (E273-277) and lack of glycosylation at E154-156. To further determine the mechanisms of attenuation we assessed ALFV 3929 binding to glycosaminoglycans (GAG), a known mechanism of flaviviruses attenuation. Indeed, ALFV 3929 exhibited reduced binding to GAG-rich cells in the presence of heparin; however, low-passage ALFV isolates were relatively unaffected. Sequence comparisons between ALFV strains and structural modelling incriminated a positively-charged residue (K327) in ALFV 3929 as a GAG-binding motif. Substitution of this residue to the corresponding uncharged residue in MVEV (L), using a previously described chimeric virus containing the prM & E genes of ALFV 3929 in the backbone of MVEV (MVEV/ALFV-prME), confirmed a role for K327 in enhanced GAG binding. When the wild type residues at E327, E273-277 and E154-156 of ALFV 3929 were replaced with the corresponding residues from virulent MVEV, it revealed each motif contributed to attenuation of ALFV 3929 , with the E327/E273-277 combination most dominant. These data demonstrate that attenuation of ALFV 3929 is multifactorial and provide new insights for the rational design of attenuated flavivirus vaccines.
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فهرسة مساهمة: Keywords: Alfuy virus (ALFV); Murray Valley encephali-tis virus (MVEV); attenuation; flavivirus; glycosaminoglycan (GAG)
المشرفين على المادة: 0 (Glycosaminoglycans)
0 (Viral Envelope Proteins)
9005-49-6 (Heparin)
تواريخ الأحداث: Date Created: 20210127 Date Completed: 20210806 Latest Revision: 20210806
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7909262
DOI: 10.3390/v13020147
PMID: 33498300
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4915
DOI:10.3390/v13020147