Broad sialic acid usage amongst species D human adenovirus
Broad sialic acid usage amongst species D human adenovirus
Abstract Human adenoviruses (HAdV) are widespread pathogens causing infections of the respiratory and gastrointestinal tracts, genitourinary system and the eye. Species D (HAdV-D) are the most diverse species and cause both gastrointestinal tract infections and epidemic keratoconjunctivitis (EKC). Despite being significant pathogens, HAdV-D are understudied and knowledge around basic mechanisms of cell infection is lacking. Sialic acid (SA) usage has been proposed as a major mechanism of cell infection for EKC causing HAdV-D. Here, we provide apo state crystal structures for fiber knob proteins of 7 previously undetermined HAdV-D, and provide crystal structures of HAdV-D25, HAdV-D29 and HAdV-D53 knob proteins bound to SA. Biologically, we demonstrate that removal of cell surface SA reduced infectivity of HAdV-C5 vectors pseudotyped with HAdV-D fiber knob proteins, whilst engagement of the classical HAdV receptor, CAR was variable. Together, these data indicate an important role for SA engagement in the tropism of many HAdV-D and may facilitate the development of suitable antivirals to control EKC outbreaks.
Baker Alexander T.、Bates Emily A.、Teijeira-Crespo Alicia、Rizkallah Pierre J.、Cunliffe Tabitha G.、Mundy Rosie M.、Parker Alan L.、Moses Elise
Division of Cancer & Genetics, Cardiff University School of MedicineDivision of Cancer & Genetics, Cardiff University School of MedicineDivision of Cancer & Genetics, Cardiff University School of MedicineDivision of Infection & Immunity, Cardiff University School of MedicineDivision of Cancer & Genetics, Cardiff University School of MedicineDivision of Cancer & Genetics, Cardiff University School of MedicineDivision of Cancer & Genetics, Cardiff University School of Medicine||Systems Immunity University Research Institute, Cardiff University School of MedicineDivision of Cancer & Genetics, Cardiff University School of Medicine
基础医学分子生物学微生物学
Adenovirusreceptorsialic acidstructureinfection
Baker Alexander T.,Bates Emily A.,Teijeira-Crespo Alicia,Rizkallah Pierre J.,Cunliffe Tabitha G.,Mundy Rosie M.,Parker Alan L.,Moses Elise.Broad sialic acid usage amongst species D human adenovirus[EB/OL].(2025-03-28)[2025-05-28].https://www.biorxiv.org/content/10.1101/2023.03.21.533702.点此复制
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